ARTIFICIAL SYNAPSES
20250163126 ยท 2025-05-22
Inventors
Cpc classification
A61K47/605
HUMAN NECESSITIES
C07K2319/75
CHEMISTRY; METALLURGY
C07K14/705
CHEMISTRY; METALLURGY
A61K35/17
HUMAN NECESSITIES
C07K2319/30
CHEMISTRY; METALLURGY
A61K47/62
HUMAN NECESSITIES
C07K14/70596
CHEMISTRY; METALLURGY
A61K47/6901
HUMAN NECESSITIES
A61K47/69
HUMAN NECESSITIES
C07K2319/74
CHEMISTRY; METALLURGY
C07K2319/912
CHEMISTRY; METALLURGY
C07K2319/055
CHEMISTRY; METALLURGY
C07K2319/01
CHEMISTRY; METALLURGY
A61P37/06
HUMAN NECESSITIES
C07K2319/035
CHEMISTRY; METALLURGY
A61K47/6917
HUMAN NECESSITIES
International classification
C07K14/705
CHEMISTRY; METALLURGY
A61K35/17
HUMAN NECESSITIES
A61K47/58
HUMAN NECESSITIES
A61K47/62
HUMAN NECESSITIES
A61K47/69
HUMAN NECESSITIES
A61P37/06
HUMAN NECESSITIES
Abstract
Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clusteringan onerous barrier for traditional receptor targeting strategies.
Claims
1. A method of treating an inflammatory disorder in a subject in need thereof, the method comprising: administering a composition comprising a plurality of engineered extracellular vesicles to a subject in need thereof, wherein the engineered extracellular vesicles comprise at least one fusion protein comprising: (i) a signaling domain comprising a TSG-6 protein or a fragment thereof; and (ii) at least one vesicle targeting domain comprising a protein or a fragment thereof.
2. The method of claim 1, wherein the vesicle targeting domain is selected from a Glycosylphosphatidylinositol (GPI) anchor, a fatty acetylation site, a prenylation site, and a transmembrane domain.
3. The method of claim 2, wherein the GPI anchor is a GPI sequence from CD55 or a GPI sequence from CD59.
4. The method of claim 2, wherein the transmembrane domain is an ADAM10 transmembrane domain or a CD9 transmembrane domain.
5. The method of claim 4, wherein the CD9 transmembrane domain is a CD9 transmembrane 2 domain.
6. The method of any one of claims 1-5, wherein the signaling domain comprises a TSG-6 protein.
7. The method of any one of claims 1-5, wherein the signaling domain comprises an active fragment of a TSG-6 protein.
8. The method of any one of claims 1-7, wherein the fusion protein further comprises a fragment crystallizable region (Fc) domain.
9. The method of any one of claims 1-8, wherein the signaling domain is displayed on the exterior of the engineered extracellular vesicle.
10. The method of any one of claims 1-9, wherein the inflammatory disorder is an acute inflammatory disorder.
11. The method of any one of claims 1-9, wherein the inflammatory disorder is a chronic inflammatory disorder.
12. The method of any one of claims 1-11, wherein the inflammatory disorder is an ocular inflammatory disorder.
13. The method of any one of claims 1-12, wherein the inflammatory disorder is caused by an injury, an infection, or a disease.
14. The method of claim 13, wherein the injury is caused by a trauma selected from a laceration injury, a crush injury, and an impact injury.
15. The method of claim 13, wherein the disease is an age-related degeneration.
16. The method of any one of claims 1-15, wherein the administration is parenteral or mucosal.
17. The method of any one of claims 1-16, wherein the administration is intranasal.
18. The method of any one of claims 1-17, wherein the composition further comprises a pharmaceutically acceptable carrier.
19. The method of any one of claims 1-18, wherein the composition is formulated as a lyophilized formulation for administration.
20. The method of any one of claims 1-18, wherein the method further comprises administering an additional therapeutic agent.
21. An engineered extracellular vesicle comprising an engineered fusion protein, wherein the engineered extracellular vesicles comprise at least one fusion protein comprising: (i) a signaling domain comprising a TSG-6 protein or a fragment thereof; and (ii) at least one vesicle targeting domain comprising a protein or a fragment thereof.
22. A method of manufacturing a population of engineered extracellular vesicles of claim 1, comprising the steps of: genetically engineering a cell line selected from the group consisting of HEK293, PER.C, fibrosarcoma HT-1080, HuH7, and mesenchymal stem cells, with a vector or vectors comprising a gene encoding the signaling domain and a gene encoding the at least one vesicle targeting domain, to produce a genetically engineered cell line; and generating, separating, and purifying the population of engineered extracellular vesicles from the genetically engineered cell line.
Description
A BRIEF DESCRIPTION OF THE DRAWINGS
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[0066] Type II membrane proteins wherein the N-Terminus is on the exterior while the C-Terminus is on the interior.
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DETAILED DESCRIPTION
[0094] The compositions and methods provided herein are based, in part, on the discovery that engineered extracellular vesicles (e.g., exosomes) expressing an engineered fusion protein (e.g., PD-L1) reduces inflammation in an animal model of experimental autoimmune uveoretinitis (EAU), an autoimmune disorder. The compositions and methods provided herein are further based, in part, on the discovery that engineered extracellular vesicles produce enhanced signaling compared to an equal quantity of recombinant ligand. Since some cellular receptors, (e.g., PD-1) require clustering or super-clustering to promote a signaling response, it stands to reason that extracellular vesicles engineered to express ligands on their surface wherein the ligands may engage target receptors on target cells and promote clustering of said target receptors thereby promoting a signal response on said target cell.
[0095] In one aspect, provided herein is an engineered extracellular vesicle comprising: at least one fusion polypeptide comprising: at least one protein of interest (POI) domain; and at least one vesicle targeting domain. In some embodiments of any of the aspects, the engineered extracellular vesicle is an exosome. In some embodiments, of any of the aspects, the fusion protein further comprises at least one linker. In some embodiments of any of the aspects, the POI domain can substantially bind to a target polypeptide. In some embodiments of any of the aspects provided herein, the engineered extracellular vesicle is an artificial synapse.
[0096] Generally, the extracellular vesicles (e.g., exosomes) provided herein are produced by contacting a population of cells with a nucleic acid construct encoding the fusion proteins provided herein and isolating a plurality of extracellular vesicles. The extracellular vesicles can then be purified by methods provided herein and are formulated for therapeutic use, including but not limited to, for the treatment of autoimmune diseases, cancer, or modulating inflammation in a subject.
[0097] The compositions and methods provided herein are specifically designed to exploit the membrane trafficking mechanisms of extracellular vesicles and rely on the hallmark biophysical and biochemical properties of extracellular vesicles, such as exosomes. The vesicles/artificial synapses provided herein are specifically engineered to induce/agonize and propagate biological signaling via a target polypeptide (e.g., by activating a receptor or enzyme or agonizing said receptor or enzyme). Alternatively, the engineered extracellular vesicles provided herein can act as cellular decoys or to reduce or antagonize biological signaling, e.g., by blocking an endogenous ligand from binding to a target cellular receptor and preventing activation of the receptor.
[0098] Engineering of the extracellular vesicles provided herein extends these capabilities significantly by incorporating sticky binders attaching to extracellular vesicles such as exosomes, further coupled with signaling domains of choice. For example, attachment of sticky binders to exosomes, along with their linked signaling domains, allows for receptor clustering for biological signal induction/agonism and propagation not otherwise possible. In this aspect, the aforementioned design achieves the aim of an engineered extracellular vesicle by inducing the desired biological signaling in a target recipient cell.
[0099] Various aspects and embodiments of the compositions and methods are provided herein in detail below.
Engineered Extracellular Vesicle (EV) Compositions
[0100] The compositions provided herein comprises at least one extracellular vesicle (also termed artificial synapse or abbrv: EV), wherein the extracellular vesicle comprises at least one fusion polypeptide or a plurality of fusion polypeptides comprising: at least one vesicle targeting domain (e.g., sticky binders); and at least one protein of interest domain or a fragment thereof (also termed signaling domains).
[0101] Extracellular vesicles (EVs) are lipid particles that are released from various cell types that function to transfer cargo such as nucleic acids and proteins to other cells. EVs are not able to replicate but serve as cell messengers. EV-mediated signals can be transmitted by all the different biomolecule categoriesprotein, lipids, nucleic acids and sugarsand the unique package of this information provides both protection and the option of simultaneous delivery of multiple different messengers even to sites remote to the vesicular origin. See, e.g., Yez-M M, Siljander P R, Andreu Z, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015; 4:27066. Published 2015 May 14. doi:10.3402/jev.v4.27066, which is incorporated herein by reference in its entirety. Furthermore, there is an increasing amount of evidence that shows that EVs can modulate a milieu of cellular signaling processes. See, e.g., Yadid et al. Science Translation Medicine (2020); Cerqueira de Abreu et al. Nature Reviews Cardiology (2020); Zhang W. et al. Protein J. (2019); Zha Q B et al. Tumor Biology. February 2017; Tan et al. (2016) Recent advances of exosomes in immune modulation and autoimmune diseases, Autoimmunity, 49:6, 357-365; Kalluri R, LeBleu V S. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb. 7; 367(6478):eaau6977, which are incorporated herein by reference in their entireties.
[0102] There are various types of extracellular vesicles that are named for their site of origin in a cell, size, and structural and/or functional properties. In some embodiments of any of the aspects provided herein, the extracellular vesicle is an exosome, ectosome, macrovesicle, microparticle, apoptotic body, vesicular organelle, oncosome, exosphere, exomeres, or cell derived nanovesicle (CDN) ((e.g., by genesis via grating or shearing cells), liposomes or the like known by one of ordinary skill in the art. In various embodiments, the extracellular vesicle comprises a phospholipid bilayer with an exterior phospholipid layer and an interior phospholipid layer, wherein the exterior phospholipid layer has an external surface and an internal surface, wherein the interior phospholipid layer has an internal surface and an external surface, and the internal surface of the exterior phospholipid layer faces the internal surface of the interior phospholipid layer, and the phospholipid bilayer encloses an internal space, wherein the external surface of the interior phospholipid layer faces the internal space and wherein the external surface of the exterior phospholipid layer faces an extracellular environment, and the external surface of the inner phospholipid layer is the internal surface of the extracellular vesicle.
[0103] In various embodiments, the extracellular vesicles range in size from 30 nanometers (nm) to 300 nm. In various embodiments, the plurality of EVs range in size from about 30 nm to about 150 nm. In various embodiments, the plurality of EVs or artificial synapses includes one or more artificial synapses that are about 10 nm to about 250 nm in diameter, including those about 10 nm to about 15 nm, about 15 nm to about 20 nm, about 20 nm to about 25 nm, about 25 nm to about 30 nm, about 30 nm to about 35 nm, about 35 nm to about 40 nm, about 40 nm to about 50 nm, about 50 nm to about 60 nm3 about 60 nm to about 70 nm, about 70 nm to about 80 nm, about 80 nm to about 90 nm, about 90 nm to about 95 nm, about 95 nm to about 100 nm, about 100 nm to about 105 nm, about 105 nm to about 110 nm, about 110 nm to about 115 nm, about 115 nm to about 120 nm, about 120 nm to about 125 nm, about 125 nm to about 130 nm, about 130 nm to about 135 nm, about 135 nm to about 140 nm, about 140 nm to about 145 nm, about 145 nm to about 150 nm, about 150 to about 200 nm, about 200 nm to about 250 nm, about 250 nm or more.
[0104] In some embodiments of any of the aspects provided herein, the EV is an exosome. Exosomes are membrane-bound EVs that are produced in the endosomal compartment of most eukaryotic cells. As used herein, the term exosome refers to a species of extracellular vesicle between about 20 nm to about 400 m in diameter, e.g, about 30 nm-200 nm in diameter by inward invagination of a portion of a membrane of an endosome (for example an early or late endosome), wherein the endosome is within a cell comprising a plasma membrane, and the exosome is released from the cell upon fusion of another portion of the endosome membrane with the plasma membrane. An exosome may refer to a species of extracellular vesicle between 20 nm-400 M in diameter, more preferably 30 nm-200 nm in diameter, that originates by budding of a portion of a plasma membrane from a cell wherein the budded portion of the plasma membrane is released to the extracellular environment.
[0105] The EVs (e.g., exosomes or cell derived vesicles) provided herein may comprise cargo, for example, peptides, proteins, nucleic acids, lipids, metabolites, carbohydrates, biomolecules, small molecules, large molecules, vesicles, organelles, or fragments thereof. Exosome cargo may be located within the internal space of the exosome. EV cargo may be membrane bound spanning one or both layers of the exosome phospholipid bilayer (for example a transmembrane protein). EV cargo may be in contact with the exterior or interior surface of the exosome, for example through a covalent bond or a non-covalent bond. The phospholipid bilayer of the EV or exosome provided herein may comprise one or more transmembrane proteins, wherein a portion of the one or more transmembrane membrane proteins is located within the internal space of the exosome. The phospholipid bilayer of the EV or exosome provided herein may comprise one or more transmembrane proteins, wherein a portion of the one or more transmembrane membrane proteins traverses the EV phospholipid bilayer. The phospholipid bilayer of the EV may comprise one or more transmembrane proteins, wherein the one or more transmembrane membrane proteins comprises a domain on the exterior of the exosome.
[0106] In some embodiments of any of the aspects, the extracellular vesicles or exosomes provided herein endogenously express CD81+, CD82+, CD37+, CD63+, CD9+, CD151+, CD105+, or any combination thereof. In various embodiments, the plurality of artificial synapses includes one or more artificial synapses expressing a biomarker. In certain embodiments, the biomarkers are tetraspanins. In other embodiments, the tetraspanins are one or more selected from the group including CD63, CD81, CD82, CD53, CD151, and CD37. In other embodiments, the artificial synapses express one or more lipid raft associated proteins (e.g., glycosylphosphatidylinositol-anchored proteins and flotillin), cholesterol, sphingolipids such as sphingomyelin, and/or hexosylceramides.
[0107] In other embodiments, the biological protein is related to exosome formation and packaging of cytosolic proteins, e.g., Hsp70, Hsp90, 14-3-3 epsilon, PKM2, GW182 and AGO2. In certain embodiments, the artificial synapses express CD63, HSP70, CD105 or combinations thereof. In other embodiments, the artificial synapses do not express CD9 or CD81, or express neither. For example, plurality of artificial synapses can include one or more artificial synapses that are CD63+, HSP+, CD105+, CD9, and CD81.
[0108] The EVs provided herein are specifically engineered to express fusion polypeptides that elicit biological signaling via a target cell. In some embodiments, the fusion polypeptide is overexpressed to elicit a biological response on a target cell or target polypeptide. The engineered EV comprises at least one fusion polypeptide and can comprise a plurality of the same or different fusion polypeptides provided herein. The fusion polypeptides provided herein comprise a protein of interest domain, also termed the signaling domain.
[0109] The fusion polypeptides provided herein can comprise one or more of a protein of interest domain, such that expression of said fusion polypeptide is permitted and that the number of POI domains does not impede protein expression or folding. Furthermore, the EVs provided herein can express more than one fusion protein (e.g., encoded by multiple different nucleic acid constructs). One of skill in the art can appreciate that an engineered EV can include one or more combinations of different signaling domains and/or vesicle targeting domains, or that one can use a plurality of engineered EVs, each including one or more vesicle targeting domains and one or more signaling domains.
[0110] In some embodiments, the EVs provided herein comprise one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, or ten or more fusion proteins. The fusion proteins can be encoded by the same vector or separate vectors. In some embodiments of any of the aspects, the engineered extracellular vesicle comprises at least two POI domains and/or at least two vesicle targeting domains.
[0111] In some embodiments, the fusion polypeptide comprises one or more, two or more, three or more, four or more, five or more, or six or more POI domains on the same polypeptide or nucleic acid construct encoding said polypeptide. For example, the fusion polypeptides provided herein can express a fusion polypeptide encoding one or more, two or more, three or more, four or more, five or more, or six or more signaling domains. In another example, the fusion polypeptides provided herein can express a fusion polypeptide encoding an immune checkpoint protein or a protein involved in immune or cell synapse or any combination or fragment thereof.
[0112] In some embodiments, the EV comprises one or more, two or more, three or more, four or more, five or more, or six or more fusion polypeptides on the same EV. For example, EVs comprising one or more, two or more, three or more, four or more, five or more, or six or more fusion polypeptides wherein the fusion polypeptides encode a signaling domain. In another example, EVs comprising one or more, two or more, three or more, four or more, five or more, or six or more fusion polypeptides wherein the fusion polypeptides encode for one or more immune checkpoint proteins or proteins involved in immune or cell synapse, or any combination or fragment thereof.
[0113] In various embodiments, the signaling domain is a protein or peptide of interest, or a fragment thereof. In various embodiments, the protein of interest (signaling domain) is an immune checkpoint protein. The terms immune checkpoint protein or protein involved in immune or cell synapse can include but are not limited to adenosine A2A receptor (A2AR), Galectin 9, fibrinogen-like protein 1 (FGL-1), platelet endothelial adhesion factor-1 (PECAM-1), tumor necrosis factor gene 6 protein (TSG-6), Stabilin-1 (STAB-1) also known as Clever-1, Neuropilin 1 (NRP1), Neuropilin 2 (NRP2), semaphorin-3A (SEMA3A), semaphorin-3F (SEMA3F), repulsive guidance molecule B (RGMB) also known as DRG11, T-cell immunoglobulin and mucin domain 3 (TIM-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), human leukocyte antigen (HLA) class I, HLA class II, high mobility group protein B1 (HMGB1), phosphatidylserine, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1), T-cell receptor (TCR), Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1), SHP-2, F-Box protein 38 (FBXO38), signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) also known as SH2D1A, B7RP1, indoleamine 2,3-dioxygenase (IDO), NADH oxidase 2 (NOX2), tumor necrosis factor receptor (TNFR) superfamily member 18 (TNFRSF18) (also known as activation inducible TNFR family receptor (AITR), glucocorticoid-induced TNFR related (GITR) protein, and CD357), B7-H4 also known as V-set domain containing T-cell activator inhibitor (VTCN1), B7-H5 (also known as V-domain Ig suppressor of T-cell activation (VISTA), platelet receptor Gi24, and stress induced secreted protein 1 (SISP1), B7-H6 (also known as NCR3LG1), B7-H7 (also known as human endogenous retrovirus-H (HERV-H) long terminal repeat-associating protein 2 (HHLA2), apelin receptor (APLNR), interferon gamma (IFN ) receptor, programmed cell death-1 (PD-1), Protein Wnt-5a (WNT5A), serine/threonine-protein kinase PAK4, interleukin 6 (IL-6), interleukin-10 (IL-10), NKG2 family of C-type lectin receptors (for example NKG2A, B, C, D, E, F and H), ligands of NKG2 family, killer cell immunoglobulin-like receptors, CD-2, cluster of differentiation 4 (CD4), CD8, CD27, CD27 ligand (CD27L, also known as CD70), CD28, CD28H (also known as transmembrane and immunoglobulin domain containing 2 (TMIGD2) and Ig containing and proline-rich receptor-1 (IGPR1)), CD39, CD40, CD44, integrin associated protein (CD47), carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1 also known as CD66a), CD73, B7-1 (also known as CD80), B7-2 (also known as CD86), CD94, CD96, immunoglobulin superfamily member 2 (IGSF2) also known as CD101, nectin cell adhesion molecule 2 (NECTIN2) (also known as herpesvirus entry mediator B (HVEB), poliovirus receptor related 2 (PRR2, PVRL2 and PVRR2) and CD112), poliovirus receptor related immunoglobulin domain containing protein (PVIRG) also known as CD112R, CD122 (also known as IL5RB and P70-75), OX40 (also known as tumor necrosis factor receptor superfamily member 4 (TNFRSF4) and CD134), OX40 ligand (OX40L), 4-1BB (also known as CD137), CD134 (also known as 4-1BB ligand (4-1BBL) and as tumor necrosis factor ligand superfamily member 9 (TNFSF9) and CD137L), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) also known as CD152, CD154 (also known as CD40L), poliovirus receptor (PVR) also known as CD155, killer-cell immunoglobulin-like receptors (KIRs) (for example but not limited to CD158 family, CD158a, CD158g, CD158h, KIR2DL1, KIR2DS1, KIRDS3, and KIR2DS5), CD160, signal-regulatory protein alpha (SIRPa) also known as CD172a, OX-2 also known as CD200, CD200R, lymphocyte-activation gene 3 (LAG-3) also known as CD223, CD226, OX40L also known as CD252, herpes virus entry mediator (HVEM) also known as tumor necrosis factor receptor superfamily member 14 (TNFRSF14) and CD270, B- and T-lymphocyte attenuator (BTLA) also known as CD272, programmed cell death ligand-2 (PD-L2) (also known as B7-DC, PDCD1LG2, and CD273), programmed cell death-ligand 1 (PD-L1) (also known as B7-H1 and CD274), B7-H2 (also known as inducible T-cell co-stimulator ligand (ICOSLG), B7RP1, and CD275), B7-H3 also known as CD276, inducible T-cell co-stimulator (ICOS) also known as CD278, programed cell death protein 1 (PD-1) also known as CD279, leukocyte-associated Ig-like receptor-1 (LAIR-1) also known as CD305, collagen family of proteins (for example but not limited to collagen I, collagen II, collagen III alpha 1, collagen IV, collagen XXIII alpha 1, collagen XXV alpha 1), sialic acid-binding immunoglobulin-type lectin 7 (SIGLEC7) also known as CD328, sialic acid-binding immunoglobulin-type lectin 7 (SIGLEC9) also known as CD329, natural cytotoxicity triggering receptor 3 (NKp30) also known as CD337, or any isoform, fragment, variation thereof, or a ligand to the aforementioned proteins thereof, or the like known by one of ordinary skill in the art. All variants are encompassed by the present invention.
[0114] In some embodiments of any of the aspects provided herein, the protein of interest domain (POI domain) comprises a polypeptide or a fragment thereof or a nucleic acid encoding said polypeptide or fragment thereof selected from the group consisting of. Table 1 (below). Non-limiting examples of nucleic acid sequences that encode the POI domains provided herein are also provided in Table 1.
TABLE-US-00001 TABLE1 TypeIProteinsofInterestAminoAcidSequence Proteinof TranscriptSequence(SEQIDNO:) Interest AminoAcidSequence(SEQIDNO:) Human >NM_014143.4HomosapiensCD274molecule(CD274), Programmed transcriptvariant1,mRNA death-ligand AGTTCTGCGCAGCTTCCCGAGGCTCCGCACCAGCCGCGCTTCTGTCCGCCTGCAGGG 1(PD-L1) CATTCCAGAAAGATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTG CTGAACGCATTTACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGC AATATGACAATTGAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTA ATTGTCTATTGGGAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAA GACCTGAAGGTTCAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAG CTCTCCCTGGGAAATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGG GTGTACCGCTGCATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAA GTCAATGCCCCATACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACC TCTGAACATGAACTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGG ACAAGCAGTGACCATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGA GAGGAGAAGCTTTTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAG ATTTTCTACTGCACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTG GTCATCCCAGAACTACCTCTGGCACATCCTCCAAATGAAAGGACTCACTTGGTAATT CTGGGAGCCATCTTATTATGCCTTGGTGTAGCACTGACATTCATCTTCCGTTTAAGA AAAGGGAGAATGATGGATGTGAAAAAATGTGGCATCCAAGATACAAACTCAAAGAAG CAAAGTGATACACATTTGGAGGAGACGTAATCCAGCATTGGAACTTCTGATCTTCAA GCAGGGATTCTCAACCTGTGGTTTAGGGGTTCATCGGGGCTGAGCGTGACAAGAGGA AGGAATGGGCCCGTGGGATGCAGGCAATGTGGGACTTAAAAGGCCCAAGCACTGAAA ATGGAACCTGGCGAAAGCAGAGGAGGAGAATGAAGAAAGATGGAGTCAAACAGGGAG CCTGGAGGGAGACCTTGATACTTTCAAATGCCTGAGGGGCTCATCGACGCCTGTGAC AGGGAGAAAGGATACTTCTGAACAAGGAGCCTCCAAGCAAATCATCCATTGCTCATC CTAGGAAGACGGGTTGAGAATCCCTAATTTGAGGGTCAGTTCCTGCAGAAGTGCCCT TTGCCTCCACTCAATGCCTCAATTTGTTTTCTGCATGACTGAGAGTCTCAGTGTTGG AACGGGACAGTATTTATGTATGAGTTTTTCCTATTTATTTTGAGTCTGTGAGGTCTT CTTGTCATGTGAGTGTGGTTGTGAATGATTTCTTTTGAAGATATATTGTAGTAGATG TTACAATTTTGTCGCCAAACTAAACTTGCTGCTTAATGATTTGCTCACATCTAGTAA AACATGGAGTATTTGTAAGGTGCTTGGTCTCCTCTATAACTACAAGTATACATTGGA AGCATAAAGATCAAACCGTTGGTTGCATAGGATGTCACCTTTATTTAACCCATTAAT ACTCTGGTTGACCTAATCTTATTCTCAGACCTCAAGTGTCTGTGCAGTATCTGTTCC ATTTAAATATCAGCTTTACAATTATGTGGTAGCCTACACACATAATCTCATTTCATC GCTGTAACCACCCTGTTGTGATAACCACTATTATTTTACCCATCGTACAGCTGAGGA AGCAAACAGATTAAGTAACTTGCCCAAACCAGTAAATAGCAGACCTCAGACTGCCAC CCACTGTCCTTTTATAATACAATTTACAGCTATATTTTACTTTAAGCAATTCTTTTA TTCAAAAACCATTTATTAAGTGCCCTTGCAATATCAATCGCTGTGCCAGGCATTGAA TCTACAGATGTGAGCAAGACAAAGTACCTGTCCTCAAGGAGCTCATAGTATAATGAG GAGATTAACAAGAAAATGTATTATTACAATTTAGTCCAGTGTCATAGCATAAGGATG ATGCGAGGGGAAAACCCGAGCAGTGTTGCCAAGAGGAGGAAATAGGCCAATGTGGTC TGGGACGGTTGGATATACTTAAACATCTTAATAATCAGAGTAATTTTCATTTACAAA GAGAGGTCGGTACTTAAAATAACCCTGAAAAATAACACTGGAATTCCTTTTCTAGCA TTATATTTATTCCTGATTTGCCTTTGCCATATAATCTAATGCTTGTTTATATAGTGT CTGGTATTGTTTAACAGTTCTGTCTTTTCTATTTAAATGCCACTAAATTTTAAATTC ATACCTTTCCATGATTCAAAATTCAAAAGATCCCATGGGAGATGGTTGGAAAATCTC CACTTCATCCTCCAAGCCATTCAAGTTTCCTTTCCAGAAGCAACTGCTACTGCCTTT CATTCATATGTTCTTCTAAAGATAGTCTACATTTGGAAATGTATGTTAAAAGCACGT ATTTTTAAAATTTTTTTCCTAAATAGTAACACATTGTATGTCTGCTGTGTACTTTGC TATTTTTATTTATTTTAGTGTTTCTTATATAGCAGATGGAATGAATTTGAAGTTCCC AGGGCTGAGGATCCATGCCTTCTTTGTTTCTAAGTTATCTTTCCCATAGCTTTTCAT TATCTTTCATATGATCCAGTATATGTTAAATATGTCCTACATATACATTTAGACAAC CACCATTTGTTAAGTATTTGCTCTAGGACAGAGTTTGGATTTGTTTATGTTTGCTCA AAAGGAGACCCATGGGCTCTCCAGGGTGCACTGAGTCAATCTAGTCCTAAAAAGCAA TCTTATTATTAACTCTGTATGACAGAATCATGTCTGGAACTTTTGTTTTCTGCTTTC TGTCAAGTATAAACTTCACTTTGATGCTGTACTTGCAAAATCACATTTTCTTTCTGG AAATTCCGGCAGTGTACCTTGACTGCTAGCTACCCTGTGCCAGAAAAGCCTCATTCG TTGTGCTTGAACCCTTGAATGCCACCAGCTGTCATCACTACACAGCCCTCCTAAGAG GCTTCCTGGAGGTTTCGAGATTCAGATGCCCTGGGAGATCCCAGAGTTTCCTTTCCC TCTTGGCCATATTCTGGTGTCAATGACAAGGAGTACCTTGGCTTTGCCACATGTCAA GGCTGAAGAAACAGTGTCTCCAACAGAGCTCCTTGTGTTATCTGTTTGTACATGTGC ATTTGTACAGTAATTGGTGTGACAGTGTTCTTTGTGTGAATTACAGGCAAGAATTGT GGCTGAGCAAGGCACATAGTCTACTCAGTCTATTCCTAAGTCCTAACTCCTCCTTGT GGTGTTGGATTTGTAAGGCACTTTATCCCTTTTGTCTCATGTTTCATCGTAAATGGC ATAGGCAGAGATGATACCTAATTCTGCATTTGATTGTCACTTTTTGTACCTGCATTA ATTTAATAAAATATTCTTATTTATTTTGTTACTTGGTACACCAGCATGTCCATTTTC TTGTTTATTTTGTGTTTAATAAAATGTTCAGTTTAACATCCCA(SEQIDNO: 1) >NP_054862.1programmedcelldeath1ligand1isoforma precursor[Homosapiens] MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSDT HLEET(SEQIDNO:2) MousePD-L1 >NM_021893.3MusmusculusCD274antigen(Cd274),mRNA GAAATCGTGGTCCCCAAGCCTCATGCCAGGCTGCACTTGCACGTCGCGGGCCAGTCT CCTCGCCTGCAGATAGTTCCCAAAACATGAGGATATTTGCTGGCATTATATTCACAG CCTGCTGTCACTTGCTACGGGCGTTTACTATCACGGCTCCAAAGGACTTGTACGTGG TGGAGTATGGCAGCAACGTCACGATGGAGTGCAGATTCCCTGTAGAACGGGAGCTGG ACCTGCTTGCGTTAGTGGTGTACTGGGAAAAGGAAGATGAGCAAGTGATTCAGTTTG TGGCAGGAGAGGAGGACCTTAAGCCTCAGCACAGCAACTTCAGGGGGAGAGCCTCGC TGCCAAAGGACCAGCTTTTGAAGGGAAATGCTGCCCTTCAGATCACAGACGTCAAGC TGCAGGACGCAGGCGTTTACTGCTGCATAATCAGCTACGGTGGTGCGGACTACAAGC GAATCACGCTGAAAGTCAATGCCCCATACCGCAAAATCAACCAGAGAATTTCCGTGG ATCCAGCCACTTCTGAGCATGAACTAATATGTCAGGCCGAGGGTTATCCAGAAGCTG AGGTAATCTGGACAAACAGTGACCACCAACCCGTGAGTGGGAAGAGAAGTGTCACCA CTTCCCGGACAGAGGGGATGCTTCTCAATGTGACCAGCAGTCTGAGGGTCAACGCCA CAGCGAATGATGTTTTCTACTGTACGTTTTGGAGATCACAGCCAGGGCAAAACCACA CAGCGGAGCTGATCATCCCAGAACTGCCTGCAACACATCCTCCACAGAACAGGACTC ACTGGGTGCTTCTGGGATCCATCCTGTTGTTCCTCATTGTAGTGTCCACGGTCCTCC TCTTCTTGAGAAAACAAGTGAGAATGCTAGATGTGGAGAAATGTGGCGTTGAAGATA CAAGCTCAAAAAACCGAAATGATACACAATTCGAGGAGACGTAAGCAGTGTTGAACC CTCTGATCGTCGATTGGCAGCTTGTGGTCTGTGAAAGAAAGGGCCCATGGGACATGA GTCCAAAGACTCAAGATGGAACCTGAGGGAGAGAACCAAGAAAGTGTTGGGAGAGGA GCCTGGAACAACGGACATTTTTTCCAGGGAGACACTGCTAAGCAAGTTGCCCATCAG TCGTCTTGGGAAATGGATTGAGGGTTCCTGGCTTAGCAGCTGGTCCTTGCACAGTGA CCTTTTCCTCTGCTCAGTGCCGGGATGAGAGATGGAGTCATGAGTGTTGAAGAATAA GTGCCTTCTATTTATTTTGAGTCTGTGTGTTCTCACTTTGGGCATGTAATTATGACT GGTGAATTCTGACGACATGATAGATCTTAAGATGTAGTCACCAAACTCAACTGCTGC TTAGCATCCTCCGTAACTACTGATACAAGCAGGGAACACAGAGGTCACCTGCTTGGT TTGACAGGCTCTTGCTGTCTGACTCAAATAATCTTTATTTTTCAGTCCTCAAGGCTC TTCGATAGCAGTTGTTCTGTATCAGCCTTATAGGTGTCAGGTATAGCACTCAACATC TCATCTCATTACAATAGCAACCCTCATCACCATAGCAACAGCTAACCTCTGTTATCC TCACTTCATAGCCAGGAAGCTGAGCGACTAAGTCACTTGCCCACAGAGTATCAGCTC TCAGATTTCTGTTCTTCAGCCACTGTCCTTTCAGGATAGAATTTGTCGTTAAGAAAT TAATTTAAAAACTGATTATTGAGTAGCATTGTATATCAATCACAACATGCCTTGTGC ACTGTGCTGGCCTCTGAGCATAAAGATGTACGCCGGAGTACCGGTCGGACATGTTTA TGTGTGTTAAATACTCAGAGAAATGTTCATTAACAAGGAGCTTGCATTTTAGAGACA CTGGAAAGTAACTCCAGTTCATTGTCTAGCATTACATTTACCTCATTTGCTATCCTT GCCATACAGTCTCTTGTTCTCCATGAAGTGTCATGAATCTTGTTGAATAGTTCTTTT ATTTTTTAAATGTTTCTATTTAAATGATATTGACATCTGAGGCGATAGCTCAGTTGG TAAAACCCTTTCCTCACAAGTGTGAAACCCTGAGTCTTATCCCTAGAACCCACATAA AAAACAGTTGCGTATGTTTGTGCATGCTTTTGATCCCAGCACTAGGGAGGCAGAGGC AGGCAGATCCTGAGCTCTCATTGACCACCCAGCCTAGCCTACATGGTTAGCTCCAGG CCTACAGGAGCTGGCAGAGCCTGAAAAACGATGCCTAGACACACACACACACACACA CACACACACACACACACACACACACCATGTACTCATAGACCTAAGTGCACCCTCCTA CACATGCACACACATACAATTCAAACACAAATCAACAGGGAATTGTCTCAGAATGGT CCCCAAGACAAAGAAGAAGAAAAACACCAAACCAGCTCTATTCCCTCAGCCTATCCT CTCTACTCCTTCCTAGAAGCAACTACTATTGTTTTTGTATATAAATTTACCCAACGA CAGTTAATATGTAGAATATATATTAAAGTGTCTGTCAATATATATTATCTCTTTCTT TCTTTCTTCCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTT CTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTTCTTTCTTTCTTTCTTTT TTTCTGTCTATCTGTACCTAAATGGTTGCTCACTATGCATTTTCTGTGCTCTTCGCC CTTTTTATTTAATGTATGGATATTTATGCTGCTTCCAGAATGGATCTAAAGCTCTTT GTTTCTAGGTTTTCTCCCCCATCCTTCTAGGCATCTCTCACACTGTCTAGGCCAGAC ACCATGTCTGCTGCCTGAATCTGTAGACACCATTTATAAAGCACGTACTCACCGAGT TTGTATTTGGCTTGTTCTGTGTCTGATTAAAGGGAGACCATGAGTCCCCAGGGTACA CTGAGTTACCCCAGTACCAAGGGGGAGCCTTGTTTGTGTCTCCATGGCAGAAGCAGG CCTGGAGCCATTTTGGTTTCTTCCTTGACTTCTCTCAAACACAGACGCCTCACTTGC TCATTACAGGTTCTCCTTTGGGAATGTCAGCATTGCTCCTTGACTGCTGGCTGCCCT GGAAGGAGCCCATTAGCTCTGTGTGAGCCCTTGACAGCTACTGCCTCTCCTTACCAC AGGGGCCTCTAAGATACTGTTACCTAGAGGTCTTGAGGATCTGTGTTCTCTGGGGGG AGGAAAGGAGGAGGAACCCAGAACTTTCTTACAGTTTTCCTTGTTCTGTCACATGTC AAGACTGAAGGAACAGGCTGGGCTACGTAGTGAGATCCTGTCTCAAAGGAAAGACGA GCATAGCCGAACCCCCGGTGGAACCCCCTCTGTTACCTGTTCACACAAGCTTATTGA TGAGTCTCATGTTAATGTCTTGTTTGTATGAAGTTTAAGAAAATATCGGGTTGGGCA ACACATTCTATTTATTCATTTTATTTGAAATCTTAATGCCATCTCATGGTGTTGGAT TGGTGTGGCACTTTATTCTTTTGTGTTGTGTATAACCATAAATTTTATTTTGCATCA GATTGTCAATGTATTGCATTAATTTAATAAATATTTTTATTTATTAAAAAAAAAAAA AAAAA(SEQIDNO:3) >NP_068693.1programmedcelldeath1ligand1precursor [Musmusculus] MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWINSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTHWVLLGSILLFLIVVSTVLLFLRKQVRMLDVEKCGVEDTSSKNRNDT QFEET(SEQIDNO:4) HumanPD-L2 >NM_025239.4Homosapiensprogrammedcelldeath1ligand 2(PDCD1LG2),mRNA ACTCTCATGTTACGGCAAACCTTAAGCTGAATGAACAACTTTTCTTCTCTTGAATAT ATCTTAACGCCAAATTTTGAGTGCTTTTTTGTTACCCATCCTCATATGTCCCAGCTA GAAAGAATCCTGGGTTGGAGCTACTGCATGTTGATTGTTTTGTTTTTCCTTTTGGCT GTTCATTTTGGTGGCTACTATAAGGAAATCTAACACAAACAGCAACTGTTTTTTGTT GTTTACTTTTGCATCTTTACTTGTGGAGCTGTGGCAAGTCCTCATATCAAATACAGA ACATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAG CTTTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATG TGACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAG CCAGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGC TGGAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGA GGGACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGT ACCTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGG TTCCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAG AAGTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTG AAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACT TCAGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACC TTCAAAGTCAGATGGAACCCAGGACCCATCCAACTTGGCTGCTTCACATTTTCATCC CCTTCTGCATCATTGCTTTCATTTTCATAGCCACAGTGATAGCCCTAAGAAAACAAC TCTGTCAAAAGCTGTATTCTTCAAAAGACACAACAAAAAGACCTGTCACCACAACAA AGAGGGAAGTGAACAGTGCTATCTGAACCTGTGGTCTTGGGAGCCAGGGTGACCTGA TATGACATCTAAAGAAGCTTCTGGACTCTGAACAAGAATTCGGTGGCCTGCAGAGCT TGCCATTTGCACTTTTCAAATGCCTTTGGATGACCCAGCACTTTAATCTGAAACCTG CAACAAGACTAGCCAACACCTGGCCATGAAACTTGCCCCTTCACTGATCTGGACTCA CCTCTGGAGCCTATGGCTTTAAGCAAGCACTACTGCACTTTACAGAATTACCCCACT GGATCCTGGACCCACAGAATTCCTTCAGGATCCTTCTTGCTGCCAGACTGAAAGCAA AAGGAATTATTTCCCCTCAAGTTTTCTAAGTGATTTCCAAAAGCAGAGGTGTGTGGA AATTTCCAGTAACAGAAACAGATGGGTTGCCAATAGAGTTATTTTTTATCTATAGCT TCCTCTGGGTACTAGAAGAGGCTATTGAGACTATGAGCTCACAGACAGGGCTTCGCA CAAACTCAAATCATAATTGACATGTTTTATGGATTACTGGAATCTTGATAGCATAAT GAAGTTGTTCTAATTAACAGAGAGCATTTAAATATACACTAAGTGCACAAATTGTGG AGTAAAGTCATCAAGCTCTGTTTTTGAGGTCTAAGTCACAAAGCATTTGTTTTAACC TGTAATGGCACCATGTTTAATGGTGGTTTTTTTTTTGAACTACATCTTTCCTTTAAA AATTATTGGTTTCTTTTTATTTGTTTTTACCTTAGAAATCAATTATATACAGTCAAA AATATTTGATATGCTCATACGTTGTATCTGCAGCAATTTCAGATAAGTAGCTAAAAT GGCCAAAGCCCCAAACTAAGCCTCCTTTTCTGGCCCTCAATATGACTTTAAATTTGA CTTTTCAGTGCCTCAGTTTGCACATCTGTAATACAGCAATGCTAAGTAGTCAAGGCC TTTGATAATTGGCACTATGGAAATCCTGCAAGATCCCACTACATATGTGTGGAGCAG AAGGGTAACTCGGCTACAGTAACAGCTTAATTTTGTTAAATTTGTTCTTTATACTGG AGCCATGAAGCTCAGAGCATTAGCTGACCCTTGAACTATTCAAATGGGCACATTAGC TAGTATAACAGACTTACATAGGTGGGCCTAAAGCAAGCTCCTTAACTGAGCAAAATT TGGGGCTTATGAGAATGAAAGGGTGTGAAATTGACTAACAGACAAATCATACATCTC AGTTTCTCAATTCTCATGTAAATCAGAGAATGCCTTTAAAGAATAAAACTCAATTGT TATTCTTCAACGTTCTTTATATATTCTACTTTTGGGTA(SEQIDNO:5) >NP_079515.2programmedcelldeath1ligand2precursor [Homosapiens] MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITA SLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKY LTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPE GLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTWLLHIFIP FCIIAFIFIATVIALRKQLCQKLYSSKDTTKRPVTTTKREVNSAI(SEQIDNO: 6) MousePD-L2 >NM_021396.2Musmusculusprogrammedcelldeath1ligand 2(Pdcd11g2),mRNA GACCACATCATTTTTGTTCCCTTTGTTGGATATATCCTAATGTCAAATGTGGCATAT CTTTGTTGTCTCCTTCTGTCTCCCAACTAGAGAGAACACACTTACGGCTCCTGTCCC GGGCAGGTTTGGTTGTCGGTGTGATTGGCTTCCAGGGAACCTGATACAAGGAGCAAC TGTGTGCTGCCTTTTCTGTGTCTTTGCTTGAGGAGCTGTGCTGGGTGCTGATATTGA CACAGACCATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTG TAGCAGCTTTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCA GCAGTGTGAGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGA TAAGAGCCAGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCA CCCTGCTGGAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCC AAGTGAGAGATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACT ACAAGTACCTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCC TGGAGGTTCCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCC TAGCAGAAGTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGA CCCCCGAAGGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCA GAAACTTCAGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCA TTGACCCTCTGAGTCGGATGGAACCCAAAGTCCCCAGAACGTGGCCACTTCATGTTT TCATCCCGGCCTGCACCATCGCTTTGATCTTCCTGGCCATAGTGATAATCCAGAGAA AGAGGATCTAGGGGAAGCTGTATTACGGAAGAAGATCTGGACCTGCGGTCTTGGGAG TTGGAAGGATCTGATGGGAAACCCTCAAGAGACTTCTGGACTCAAAGTGAGAATCTT GCAGGACCTGCCATTTGCACTTTTGAACCCTTTGGACGGTGACCCAGGGCTCCGAAG AGGAGCTTGTAAGACTGACAATCTTCCCTCTGTCTCAAGACTCTCTGAACAGCAAGA CCCCAATGGCACTTTAGACTTACCCCTGGGATCCTGGACCCCAGTGAGGGCCTAAGG CTCCTAATGACTTTCAGGGTGAGAACAAAAGGAATTGCTCTCCGCCCCACCCCCACC TCCTGCTTTCCGCAGGGAGACATGGAAATTCCCAGTTACTAAAATAGATTGTCAATA GAGTTATTTATAGCCCTCATTTCCTCCGGGGACTTGGAAGCTTCAGACAGGGTTTTT CATAAACAAAGTCATAACTGATGTGTTTTACAGCATCCTAGAATCCTGGCAGCCTCT GAAGTTCTAATTAACTGGAAGCATTTAAGCAACACGTTAAGTACCCCCACTGTGGTA TTTGTTTCTACTTTTCTGTTTTTAAAGTGTGAGTCACAAGGTAATTGTTGTAACCTG TGATATCACTGTTTCTTGTGTCTCTTCTTTCAACTACATCTTTTAAAACAAAACGGT GTGGGGTTTGGTTGTTTTGGTGGTAGTGGTAGTGTTTCTCAGTGGTATCTCCTTAAG AAAAAAAATCATCATGCCAGTGAATTGTTTCTTCAGCCATTTCAGATGGGAAGCTGG AATAGCCTGTCCCCCAAGCTAAGCCTTCTTCCCTAGCTTTCTGCGTGATTTTACATT GAGCATTCCTGTTGCTTTGTTTCTATAACTGTAATGTGGTGATGTCATTGTTAGGGC ACTTGAGGGTGGGCGTTCTGGAAGTCCTTTCAGGTTAGTGTTTGGGGGCAGGGTTGC TCAGAATACATAAAGGTGCTAACTTAAACTGCAGCCATGGAGCTCAGTGAATTCACT AACCTTCGGGCTGTCCAAATGTGCACATTAGCTACTGTGACCCCTGTAGGTTAGGGA GCCTGAAGCCAGCTCTTTACCTGGTGTTTAGACTCAGCAGAATTTGGAGTCAATGGG ACCAAATGGTTGTGAAATTAAGATTTGAAGTGTGCATCTTATTTTATCACCATCTGC CCAACAAAACTTCAGAAAATGCCTTTGAAGCACAAAAATGTAATCGTTTATGTGAAA TCTCTGAGTTGCATTTAGATGCCCATTGCAGCAAGGTGGCTCTCTCACAGATTCCAC ACCTTAGCCTAAGATACCAGACAGCAGGACAGAGAGAAAAGTCCTTCCTGGTGTGCA AACTTCCTTACACTGGACCTCGCCTCTCAGGTGTGTGATTGGTAGGCCAAATCCCGA TAGCCAATCGGTGTTGGGTGCTTTGTCTGCTCTACTGGGAGTCCAGTGGTACAATGG ATTCTGGCAAAATGCTGCCATCTTGGCCCTCGCTGGGCTGCTTTCTAGGATATTCAT AGAGAAAGGGCCGTCCAGATCCAGTATCCTAAAATCCTGAGAGGAGAATATAAGTTA GTGTGTCTCACTATAACTATCTCTATGATCGGTCACATTACTATCTAACAGTTACCA AATACTATATGCCTAATACTGGTAAGCATTTTATACACACCATTGGATTGAATCCTC TCAAAATCCTCAAAAAGGAAGTTATTAATACCTCCATAGGCAAGGAGCCCAGAACCC AGAGAGGTCAGGCAGTCTAGTTATAGATGCCTGCTTTGTTTAGAAGTGAACAAGAGC ATCAAATTATTAATGTGCCCTGGTTATTAATGCGCCCTGGTTACCTGCTGGATGGAA CATCAAGGTGGACTTTTGGCAGTTGCATACACCCAGAGGTATTTTGGCTATTCACGG ATTAATTTCACACGAAGTGTTTCAGAGACATGTGTAGGGGAAGTCCGGGTTCAGGGG GCCTAAGATTCAAACTCTAGCTTAGCTACGTCTGACCTCCCTAAGCACTAACTTACT ATCAAAAGAATGAGCAGTAAAAGAATGGTGTTTACTGCCTGCCTTTATCAGGCAGTG AACGTGCAGCGGGCAACGAATGCTTGATAAGTGTGTGTCAGTGTGAAGTCCCATGTA CCAGCCGCTGTCCCCACTGCAAAAGCAGCAGAGCGCTCAGACATCATCAGCTGATTT ACCAGCAGCAGATTTCTTCTTCTAGTCCCATCCCTGAAGAAGCTTCCAGCCTAGGTA CATTGCATGGGCTTTGTGCTCCAGGAGTTCCTACACAGCCCTCAACTTCAACACAGG CAAAGTGCTTACTGATCCTCATGTATCTTACAGGGTCCCCTCTACCCACAATACCTC ATTGCTGGAACTTCAAATCTTCCTGAATAAAAGCTTGCCCGTGGTTTAATTA(SEQ IDNO:7) >NP_067371.1programmedcelldeath1ligand2precursor [Musmusculus] MLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRA SLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKY LTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPE GLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTWPLHVFIP ACTIALIFLAIVIIQRKRI(SEQIDNO:8) Human >NM_005214.5HomosapienscytotoxicT-lymphocyte CTLA-4 associatedprotein4(CTLA4),transcriptvariant1,mRNA (CD152) GCTTTCTATTCAAGTGCCTTCTGTGTGTGCACATGTGTAATACATATCTGGGATCAA AGCTATCTATATAAAGTCCTTGATTCTGTGTGGGTTCAAACACATTTCAAAGCTTCA GGATCCTGAAAGGTTTTGCTCTACTTCCTGAAGACCTGAACACCGCTCCCATAAAGC CATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGGAC CTGGCCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGCAAT GCACGTGGCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAGCTTTGT GTGTGAGTATGCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTGCTTCGGCA GGCTGACAGCCAGGTGACTGAAGTCTGTGCGGCAACCTACATGATGGGGAATGAGTT GACCTTCCTAGATGATTCCATCTGCACGGGCACCTCCAGTGGAAATCAAGTGAACCT CACTATCCAAGGACTGAGGGCCATGGACACGGGACTCTACATCTGCAAGGTGGAGCT CATGTACCCACCGCCATACTACCTGGGCATAGGCAACGGAACCCAGATTTATGTAAT TGATCCAGAACCGTGCCCAGATTCTGACTTCCTCCTCTGGATCCTTGCAGCAGTTAG TTCGGGGTTGTTTTTTTATAGCTTTCTCCTCACAGCTGTTTCTTTGAGCAAAATGCT AAAGAAAAGAAGCCCTCTTACAACAGGGGTCTATGTGAAAATGCCCCCAACAGAGCC AGAATGTGAAAAGCAATTTCAGCCTTATTTTATTCCCATCAATTGAGAAACCATTAT GAAGAAGAGAGTCCATATTTCAATTTCCAAGAGCTGAGGCAATTCTAACTTTTTTGC TATCCAGCTATTTTTATTTGTTTGTGCATTTGGGGGGAATTCATCTCTCTTTAATAT AAAGTTGGATGCGGAACCCAAATTACGTGTACTACAATTTAAAGCAAAGGAGTAGAA AGACAGAGCTGGGATGTTTCTGTCACATCAGCTCCACTTTCAGTGAAAGCATCACTT GGGATTAATATGGGGATGCAGCATTATGATGTGGGTCAAGGAATTAAGTTAGGGAAT GGCACAGCCCAAAGAAGGAAAAGGCAGGGAGCGAGGGAGAAGACTATATTGTACACA CCTTATATTTACGTATGAGACGTTTATAGCCGAAATGATCTTTTCAAGTTAAATTTT ATGCCTTTTATTTCTTAAACAAATGTATGATTACATCAAGGCTTCAAAAATACTCAC ATGGCTATGTTTTAGCCAGTGATGCTAAAGGTTGTATTGCATATATACATATATATA TATATATATATATATATATATATATATATATATATATATATATATATTTTAATTTGA TAGTATTGTGCATAGAGCCACGTATGTTTTTGTGTATTTGTTAATGGTTTGAATATA AACACTATATGGCAGTGTCTTTCCACCTTGGGTCCCAGGGAAGTTTTGTGGAGGAGC TCAGGACACTAATACACCAGGTAGAACACAAGGTCATTTGCTAACTAGCTTGGAAAC TGGATGAGGTCATAGCAGTGCTTGATTGCGTGGAATTGTGCTGAGTTGGTGTTGACA TGTGCTTTGGGGCTTTTACACCAGTTCCTTTCAATGGTTTGCAAGGAAGCCACAGCT GGTGGTATCTGAGTTGACTTGACAGAACACTGTCTTGAAGACAATGGCTTACTCCAG GAGACCCACAGGTATGACCTTCTAGGAAGCTCCAGTTCGATGGGCCCAATTCTTACA AACATGTGGTTAATGCCATGGACAGAAGAAGGCAGCAGGTGGCAGAATGGGGTGCAT GAAGGTTTCTGAAAATTAACACTGCTTGTGTTTTTAACTCAATATTTTCCATGAAAA TGCAACAACATGTATAATATTTTTAATTAAATAAAAATCTGTGGTGGTCGTTTTCCG GA(SEQIDNO:9) >NP_005205.2cytotoxicT-lymphocyteprotein4isoform CTLA4-TMprecursor[Homosapiens] MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFV CEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNL TIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDFLLWILAAVS SGLFFYSFLLTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN(SEQ IDNO:10) MouseCTLA- >NM_009843.4MusmusculuscytotoxicT-lymphocyte- 4(CD152) associatedprotein4(Ctla4),transcriptvariant1,mRNA CTACACATATGTAGCACGTACCTTGGATCAAAGCTGTCTATATAAAGTCCCCGAGTC TGTGTGGGTTCAAACACATCTCAAGGCTTCTGGATCCTGTTGGGTTTTACTCTGCTC CCTGAGGACCTCAGCACATTTGCCCCCCAGCCATGGCTTGTCTTGGACTCCGGAGGT ACAAAGCTCAACTGCAGCTGCCTTCTAGGACTTGGCCTTTTGTAGCCCTGCTCACTC TTCTTTTCATCCCAGTCTTCTCTGAAGCCATACAGGTGACCCAACCTTCAGTGGTGT TGGCTAGCAGCCATGGTGTCGCCAGCTTTCCATGTGAATATTCACCATCACACAACA CTGATGAGGTCCGGGTGACTGTGCTGCGGCAGACAAATGACCAAATGACTGAGGTCT GTGCCACGACATTCACAGAGAAGAATACAGTGGGCTTCCTAGATTACCCCTTCTGCA GTGGTACCTTTAATGAAAGCAGAGTGAACCTCACCATCCAAGGACTGAGAGCTGTTG ACACGGGACTGTACCTCTGCAAGGTGGAACTCATGTACCCACCGCCATACTTTGTGG GCATGGGCAACGGGACGCAGATTTATGTCATTGATCCAGAACCATGCCCGGATTCTG ACTTCCTCCTTTGGATCCTTGTCGCAGTTAGCTTGGGGTTGTTTTTTTACAGTTTCC TGGTCACTGCTGTTTCTTTGAGCAAGATGCTAAAGAAAAGAAGTCCTCTTACAACAG GGGTCTATGTGAAAATGCCCCCAACAGAGCCAGAATGTGAAAAGCAATTTCAGCCTT ATTTTATTCCCATCAACTGAAAGGCCGTTTATGAAGAAGAAGGAGCATACTTCAGTC TCTAAAAGCTGAGGCAATTTCAACTTTCCTTTTCTCTCCAGCTATTTTTACCTGTTT GTATATTTTAAGGAGAGTATGCCTCTCTTTAATAGAAAGCTGGATGCAAAATTCCAA TTAAGCATACTACAATTTAAAGCTAAGGAGCATGAACAGAGAGCTGGGATATTTCTG TTGTGTCAGAACCATTTTACTAAAAGCATCACTTGGAAGCAGCATAAGGATATAGCA TTATGGTGTGGGGTCAAGGGAACATTAGGGAATGGCACAGCCCAAAGAAAGGAAGGG GGTGAAGGAAGAGATTATATTGTACACATCTTGTATTTACCTGAGAGATGTTTATGA CTTAAATAATTTTTAAATTTTTCATGCTGTTATTTTCTTTAACAATGTATAATTACA CGAAGGTTTAAACATTTATTCACAGAGCTATGTGACATAGCCAGTGGTTCCAAAGGT TGTAGTGTTCCAAGATGTATTTTTAAGTAATATTGTACATGGGTGTTTCATGTGCTG TTGTGTATTTGCTGGTGGTTTGAATATAAACACTATGTATCAGTGTCGTCCCACAGT GGGTCCTGGGGAGGTTTGGCTGGGGAGCTTAGGACACTAATCCATCAGGTTGGACTC GAGGTCCTGCACCAACTGGCTTGGAAACTAGATGAGGCTGTCACAGGGCTCAGTTGC ATAAACCGATGGTGATGGAGTGTAAACTGGGTCTTTACACTCATTTTATTTTTTGTT TCTGCTTTTGTTTTCTTCAATGATTTGCAAGGAAACCAAAAGCTGGCAGTGTTTGTA TGAACCTGACAGAACACTGTCTTCAAGGAAATGCCTCATTCCTGAGACCAGTAGGTT TGTTTTTTTAGGAAGTTCCAATACTAGGACCCCCTACAAGTACTATGGCTCCTCGAA AACACAAAGTTAATGCCACAGGAAGCAGCAGATGGTAGGATGGGATGCACAAGAGTT CCTGAAAACTAACACTGTTAGTGTTTTTTTTTTAACTCAATATTTTCCATGAAAATG CAACCACATGTATAATATTTTTAATTAAATAAAAGTTTCTTGTGATTGTTTT(SEQ IDNO:11) >NP_033973.2cytotoxicT-lymphocyteprotein4isoform1 precursor[Musmusculus] MACLGLRRYKAQLQLPSRTWPFVALLTLLFIPVFSEAIQVTQPSVVLASSHGVASFP CEYSPSHNTDEVRVTVLRQTNDQMTEVCATTFTEKNTVGFLDYPFCSGTFNESRVNL TIQGLRAVDTGLYLCKVELMYPPPYFVGMGNGTQIYVIDPEPCPDSDFLLWILVAVS LGLFFYSFLVTAVSLSKMLKKRSPLTTGVYVKMPPTEPECEKQFQPYFIPIN(SEQ IDNO:12) Human4- >NM_003811.4HomosapiensTNFsuperfamilymember9 1BBL (TNFSF9),mRNA (CD137L) AGTCTCTCGTCATGGAATACGCCTCTGACGCTTCACTGGACCCCGAAGCCCCGTGGC CTCCCGCGCCCCGCGCTCGCGCCTGCCGCGTACTGCCTTGGGCCCTGGTCGCGGGGC TGCTGCTGCTGCTGCTGCTCGCTGCCGCCTGCGCCGTCTTCCTCGCCTGCCCCTGGG CCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGG GTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGT TTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACA GTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACA CGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGC TGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGC AGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCAC CCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACC TGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATG CCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAA TCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAACGTCCAGCCTGGGTGCAGCCCA CCTGGACAGAGTCCGAATCCTACTCCATCCTTCATGGAGACCCCTGGTGCTGGGTCC CTGCTGCTTTCTCTACCTCAAGGGGCTTGGCAGGGGTCCCTGCTGCTGACCTCCCCT TGAGGACCCTCCTCACCCACTCCTTCCCCAAGTTGGACCTTGATATTTATTCTGAGC CTGAGCTCAGATAATATATTATATATATTATATATATATATATATTTCTATTTAAAG AGGATCCTGAGTTTGTGAATGGACTTTTTTAGAGGAGTTGTTTTGGGGGGGGGGGGG TCTTCGACATTGCCGAGGCTGGTCTTGAACTCCTGGACTTAGACGATCCTCCTGCCT CAGCCTCCCAAGCAACTGGGATTCATCCTTTCTATTAATTCATTGTACTTATTTGCT TATTTGTGTGTATTGAGCATCTGTAATGTGCCAGCATTGTGCCCAGGCTAGGGGGCT ATAGAAACATCTAGAAATAGACTGAAAGAAAATCTGAGTTATGGTAATACGTGAGGA ATTTAAAGACTCATCCCCAGCCTCCACCTCCTGTGTGATACTTGGGGGCTAGCTTTT TTCTTTCTTTCTTTTTTTTGAGATGGTCTTGTTCTGTCAACCAGGCTAGAATGCAGC GGTGCAATCATGAGTCAATGCAGCCTCCAGCCTCGACCTCCCGAGGCTCAGGTGATC CTCCCATCTCAGCCTCTCGAGTAGCTGGGACCACAGTTGTGTGCCACCACACTTGGC TAACTTTTTAATTTTTTTGCGGAGACGGTATTGCTATGTTGCCAAGGTTGTTTACAT GCCAGTACAATTTATAATAAACACTCATTTTTCCTCCC(SEQIDNO:13) >NP_003802.1tumornecrosisfactorligandsuperfamily member9[Homosapiens] MEYASDASLDPEAPWPPAPRARACRVLPWALVAGLLLLLLLAAACAVFLACPWAVSG ARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPG LAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLR SAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQL TQGATVLGLFRVTPEIPAGLPSPRSE(SEQIDNO:14) Mouse4-1BBL >NM_009404.3Musmusculustumornecrosisfactor(ligand) (CD137L) superfamily,member9(Tnfsf9),mRNA ATAAAGCACGGGCACTGGCGGGAGACGTGCACTGACCGACCGTGGTAATGGACCAGC ACACACTTGATGTGGAGGATACCGCGGATGCCAGACATCCAGCAGGTACTTCGTGCC CCTCGGATGCGGCGCTCCTCAGAGATACCGGGCTCCTCGCGGACGCTGCGCTCCTCT CAGATACTGTGCGCCCCACAAATGCCGCGCTCCCCACGGATGCTGCCTACCCTGCGG TTAATGTTCGGGATCGCGAGGCCGCGTGGCCGCCTGCACTGAACTTCTGTTCCCGCC ACCCAAAGCTCTATGGCCTAGTCGCTTTGGTTTTGCTGCTTCTGATCGCCGCCTGTG TTCCTATCTTCACCCGCACCGAGCCTCGGCCAGCGCTCACAATCACCACCTCGCCCA ACCTGGGTACCCGAGAGAATAATGCAGACCAGGTCACCCCTGTTTCCCACATTGGCT GCCCCAACACTACACAACAGGGCTCTCCTGTGTTCGCCAAGCTACTGGCTAAAAACC AAGCATCGTTGTGCAATACAACTCTGAACTGGCACAGCCAAGATGGAGCTGGGAGCT CATACCTATCTCAAGGTCTGAGGTACGAAGAAGACAAAAAGGAGTTGGTGGTAGACA GTCCCGGGCTCTACTACGTATTTTTGGAACTGAAGCTCAGTCCAACATTCACAAACA CAGGCCACAAGGTGCAGGGCTGGGTCTCTCTTGTTTTGCAAGCAAAGCCTCAGGTAG ATGACTTTGACAACTTGGCCCTGACAGTGGAACTGTTCCCTTGCTCCATGGAGAACA AGTTAGTGGACCGTTCCTGGAGTCAACTGTTGCTCCTGAAGGCTGGCCACCGCCTCA GTGTGGGTCTGAGGGCTTATCTGCATGGAGCCCAGGATGCATACAGAGACTGGGAGC TGTCTTATCCCAACACCACCAGCTTTGGACTCTTTCTTGTGAAACCCGACAACCCAT GGGAATGAGAACTATCCTTCTTGTGACTCCTAGTTGCTAAGTCCTCAAGCTGCTATG TTTTATGGGGTCTGAGCAGGGGTCCCTTCCATGACTTTCTCTTGTCTTTAACTGGAC TTGGTATTTATTCTGAGCATAGCTCAGACAAGACTTTATATAATTCACTAGATAGCA TTAGTAAACTGCTGGGCAGCTGCTAGATAAAAAAAAATTTCTAAATCAAAGTTTATA TTTATATTAATATATAAAAATAAATGTGTTTGT(SEQIDNO:15) >NP_033430.1tumornecrosisfactorligandsuperfamily member9[Musmusculus] MDQHTLDVEDTADARHPAGTSCPSDAALLRDTGLLADAALLSDTVRPTNAALPTDAA YPAVNVRDREAAWPPALNFCSRHPKLYGLVALVLLLLIAACVPIFTRTEPRPALTIT TSPNLGTRENNADQVTPVSHIGCPNTTQQGSPVFAKLLAKNQASLCNTTLNWHSQDG AGSSYLSQGLRYEEDKKELVVDSPGLYYVFLELKLSPTFTNTGHKVQGWVSLVLQAK PQVDDFDNLALTVELFPCSMENKLVDRSWSQLLLLKAGHRLSVGLRAYLHGAQDAYR DWELSYPNTTSFGLFLVKPDNPWE(SEQIDNO:16) Human >NM_003820.4HomosapiensTNFreceptorsuperfamilymember HVEM 14(TNFRSF14),transcriptvariant1,DNA (CD270) ATACCGGCCCTTCCCCTCGGCTTTGCCTGGACAGCTCCTGCCTCCCGCAGGGCCCAC CTGTGTCCCCCAGCGCCGCTCCACCCAGCAGGCCTGAGCCCCTCTCTGCTGCCAGAC ACCCCCTGCTGCCCACTCTCCTGCTGCTCGGGTTCTGAGGCACAGCTTGTCACACCG AGGCGGATTCTCTTTCTCTTTCTCTTTCTCTTCTGGCCCACAGCCGCAGCAATGGCG CTGAGTTCCTCTGCTGGAGTTCATCCTGCTAGCTGGGTTCCCGAGCTGCCGGTCTGA GCCTGAGGCATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCC AAAACCGACGTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTAC GCCCCAGCTCTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGC CCCAAGTGCAGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACA GTGTGTGAACCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAG TGTCTGCAGTGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGC TCCAGGACAGAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAG GACGGGGACCACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGG GTGCAGAAGGGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGG ACCTTCTCTCCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGG CTGGTGACGAAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTATGGTGGTTTCTC TCAGGGAGCCTCGTCATCGTCATTGTTTGCTCCACAGTTGGCCTAATCATATGTGTG AAAAGAAGAAAGCCAAGGGGTGATGTAGTCAAGGTGATCGTCTCCGTCCAGCGGAAA AGACAGGAGGCAGAAGGTGAGGCCACAGTCATTGAGGCCCTGCAGGCCCCTCCGGAC GTCACCACGGTGGCCGTGGAGGAGACAATACCCTCATTCACGGGGAGGAGCCCAAAC CACTGACCCACAGACTCTGCACCCCGACGCCAGAGATACCTGGAGCGACGGCTGCTG AAAGAGGCTGTCCACCTGGCGGAACCACCGGAGCCCGGAGGCTTGGGGGCTCCGCCC TGGGCTGGCTTCCGTCTCCTCCAGTGGAGGGAGAGGTGGGGCCCCTGCTGGGGTAGA GCTGGGGACGCCACGTGCCATTCCCATGGGCCAGTGAGGGCCTGGGGCCTCTGTTCT GCTGTGGCCTGAGCTCCCCAGAGTCCTGAGGAGGAGCGCCAGTTGCCCCTCGCTCAC AGACCACACACCCAGCCCTCCTGGGCCAGCCCAGAGGGCCCTTCAGACCCCAGCTGT CTGCGCGTCTGACTCTTGTGGCCTCAGCAGGACAGGCCCCGGGCACTGCCTCACAGC CAAGGCTGGACTGGGTTGGCTGCAGTGTGGTGTTTAGTGGATACCACATCGGAAGTG ATTTTCTAAATTGGATTTGAATTCGGCTCCTGTTTTCTATTTGTCATGAAACAGTGT ATTTGGGGAGATGCTGTGGGAGGATGTAAATATCTTGTTTCTCCTCAAA(SEQID NO:17) >NP_003811.2tumornecrosisfactorreceptorsuperfamily member14isoform1precursor[Homosapiens] MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKC SPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRT ENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFS PNGTLEECQHQTKCSWLVTKAGAGTSSSHWVWWFLSGSLVIVIVCSTVGLIICVKRR KPRGDVVKVIVSVQRKRQEAEGEATVIEALQAPPDVTTVAVEETIPSFTGRSPNH (SEQIDNO:18) MouseHVEM >NM_178931.2Musmusculustumornecrosisfactorreceptor (CD270) superfamily,member14(herpesvirusentrymediator) (Tnfrsf14),mRNA GCTCTTGGCCTGAAGTTTCTTGATCAAGAAAATGGAACCTCTCCCAGGATGGGGGTC GGCACCCTGGAGCCAGGCCCCTACAGACAACACCTTCAGGCTGGTGCCTTGTGTCTT CCTTTTGAACTTGCTGCAGCGCATCTCTGCCCAGCCCTCATGCAGACAGGAGGAGTT CCTTGTGGGAGACGAGTGCTGCCCCATGTGCAACCCAGGTTACCATGTGAAGCAGGT CTGCAGTGAGCATACAGGCACAGTGTGTGCCCCCTGTCCCCCACAGACATATACCGC CCATGCAAATGGCCTGAGCAAGTGTCTGCCCTGCGGAGTCTGTGATCCAGACATGGG CCTGCTGACCTGGCAGGAGTGCTCCAGCTGGAAGGACACTGTGTGCAGATGCATCCC AGGCTACTTCTGTGAGAACCAGGATGGGAGCCACTGTTCCACATGCTTGCAGCACAC CACCTGCCCTCCAGGGCAGAGGGTAGAGAAGAGAGGGACTCACGACCAGGACACTGT ATGTGCTGACTGCCTAACAGGGACCTTCTCACTTGGAGGGACTCAGGAGGAATGCCT GCCCTGGACCAACTGCAGTGCATTTCAACAGGAAGTAAGACGTGGGACCAACAGCAC AGACACCACCTGCTCCTCCCAGGTCGTCTACTACGTTGTGTCCATCCTTTTGCCACT TGTGATAGTGGGAGCTGGGATAGCTGGATTCCTCATCTGCACGCGAAGACACCTGCA CACCAGCTCAGTGGCCAAGGAGCTGGAGCCTTTCCAGGAACAACAGGAGAACACCAT CAGGTTTCCAGTCACCGAGGTTGGGTTTGCTGAGACCGAGGAGGAGACAGCCTCCAA CTGAACAAATTCTGGGTGACAAGACACCGAGGAGACGT(SEQIDNO:19) >NP_849262.1tumornecrosisfactorreceptorsuperfamily member14precursor[Musmusculus] MEPLPGWGSAPWSQAPTDNTFRLVPCVFLLNLLQRISAQPSCRQEEFLVGDECCPMC NPGYHVKQVCSEHTGTVCAPCPPQTYTAHANGLSKCLPCGVCDPDMGLLTWQECSSW KDTVCRCIPGYFCENQDGSHCSTCLQHTTCPPGQRVEKRGTHDQDTVCADCLTGTFS LGGTQEECLPWTNCSAFQQEVRRGTNSTDTTCSSQVVYYVVSILLPLVIVGAGIAGF LICTRRHLHTSSVAKELEPFQEQQENTIRFPVTEVGFAETEEETASN(SEQID NO:20) HumanFGL1 >NM_004467.4Homosapiensfibrinogenlike1(FGL1), transcriptvariant1,mRNA AATGCAGTTACAGGATCCTGGGAAGCAGAGTGTCTGGATGGAACCTGAGCTGGGTCT CTGACTCACTTCTGACTTTAGTTTTTTCAAGGGGGAACATGGCAAAGGTGTTCAGTT TCATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAAATTTCGGCGCTCGAGGACT GTGCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGCCTGCTTGAGACCCGGGTCA AACAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAGAATGAAGTCCAGTTCCTTG ATAAAGGAGATGAGAATACTGTCATTGATCTTGGAAGCAAGAGGCAGTATGCAGATT GTTCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGATTTTACAAAATCAAACCTC TCCAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATGTCCGATGGAGGAGGATGGA CTGTAATTCAGAGACGATCTGATGGCAGTGAAAACTTTAACAGAGGATGGAAAGACT ATGAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGTGAATATTGGCTGGGCAATA AAAATCTTCACTTCTTGACCACTCAAGAAGACTACACTTTAAAAATCGACCTTGCAG ATTTTGAAAAAAATAGCCGTTATGCACAATATAAGAATTTCAAAGTTGGAGATGAAA AGAATTTCTACGAGTTGAATATTGGGGAATATTCTGGAACAGCTGGAGATTCCCTTG CGGGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGTCACCAAAGAATGAAATTCA GCACGTGGGACAGAGATCATGACAACTATGAAGGGAACTGCGCAGAAGAAGATCAGT CTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAATGGTGTATACTACAGCG GCCCCTACACGGCTAAAACAGACAATGGGATTGTCTGGTACACCTGGCATGGGTGGT GGTATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCAAATGATTTTATTCCAAATG TAATTTAATTGCTGCTGTTGGGCTTTCGTTTCTGCAATTCAGCTTTGTTTAAAGTGA TTTGAAAAATACTCATTCTGAACATATCCATGCGCAATCATGATAACTGTTGTGAGT AGTGCTTTTCATTCTTCTCACTTGCCTTTGTTACTTAATGTGCTTTCAGTACAGCAG ATATGCAATATTCACCAAATAAATGTAGACTGTGTTAATA(SEQIDNO:21) >NP_004458.3fibrinogen-likeprotein1precursor[Homo sapiens] MAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQE NEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDM SDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYT LKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWAS HQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVW YTWHGWWYSLKSVVMKIRPNDFIPNVI(SEQIDNO:22) MouseFGL1 >NM_145594.2Musmusculusfibrinogen-likeprotein1 (Fg11),mRNA GTTAGAAGTTCCTGGGAGGCTCTGTGTGGATGGACTGAGCCTAGCTAAGTCCTGATT CATTTTGACTTGAGTTCTCTCAGTGGGAAGAATGGGAAAGATTTACAGCTTCGTCCT GGTCGCCATTGCTCTGATGATGGGAAGGGAAGGTTGGGCCCTCGAGAGTGAGAACTG CTTGCGGGAGCAGGTGAGGCTCAGGGCTCAGGTGCACCAGCTTGAGACCCGGGTCAA ACAACAACAGACCATGATTGCACAGCTCTTGCATGAGAAGGAAGTCCAGTTTCTGGA TAAAGGATCGGAGAACAGTTTCATTGACCTTGGAGGCAAGAAGCAGTATGCAGATTG TTCAGAGATTTACAATGACGGATTTAAGCAGAGTGGATTTTACAAAATCAAACCTCT TCAGAGCCTGGCAGAATTCTCTGTTTATTGTGACATGTCTGATGGAGGGGGATGGAC TGTAATTCAGAGACGATCTGATGGCAGTGAGAACTTTAACAGGGGTTGGAATGACTA TGAAAATGGCTTTGGAAACTTTGTCCAAAACAATGGCGAATACTGGCTGGGTAACAA AAACATTAACTTGCTAACTATTCAAGGAGACTACACTTTAAAAATCGACCTGACAGA TTTTGAGAAAAACAGCAGCTTCGCACAATACCAAAGTTTTAAAGTTGGTGATAAAAA GTCTTTTTATGAACTAAATATTGGAGAATATTCTGGCACAGCTGGAGATTCCCTGTC AGGAACTTTTCATCCTGAAGTACAGTGGTGGGCTAGTCACCAAAGGATGAAGTTCAG CACGTGGGACAGAGATAACGACAATTACCAAGGAAACTGTGCTGAGGAAGAGCAGTC TGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAACGGTGTTTACTACCGTGG TTCCTACAGGGCAGAAACGGATAATGGTGTTGTGTGGTACACCTGGCATGGGTGGTG GTATTCCTTGAAATCTGTGGTTATGAAAATTAGGCCAAGTGATTTTATTCCAAATAT TATTTAGTTGCCCTCATTGGGATCTCCTTTCTGTAATTCATCTTGGTTTACTTGAAA ATAAATATTTGAAAAAGATATAATTCTGAATAACACA(SEQIDNO:23) >NP_663569.2fibrinogen-likeprotein1precursor[Mus musculus] MGKIYSFVLVAIALMMGREGWALESENCLREQVRLRAQVHQLETRVKQQQTMIAQLL HEKEVQFLDKGSENSFIDLGGKKQYADCSEIYNDGFKQSGFYKIKPLQSLAEFSVYC DMSDGGGWTVIQRRSDGSENFNRGWNDYENGFGNFVQNNGEYWLGNKNINLLTIQGD YTLKIDLTDFEKNSSFAQYQSFKVGDKKSFYELNIGEYSGTAGDSLSGTFHPEVQWW ASHQRMKFSTWDRDNDNYQGNCAEEEQSGWWFNRCHSANLNGVYYRGSYRAETDNGV VWYTWHGWWYSLKSVVMKIRPSDFIPNII(SEQIDNO:24) HumanOX-2 >NM_005944.7HomosapiensCD200molecule(CD200), (CD200) transcriptvariant1,mRNA AGAGCTCCAGGCGCACATCCGCAGTCAGCCACCTCGCGCGCGCCTCCAGGAGCAAGG ATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTT TGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGAT GAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAG GAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTC ACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAAC ATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAG GATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGA ACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCT GAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTC TGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAAT GGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGG AAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACC GTCAACAAAGGCTATTGGTTTTCAGTTCCGCTATTGCTAAGCATTGTTTCCCTGGTA ATTCTTCTCGTCCTAATCTCAATCTTACTGTACTGGAAACGTCACCGGAATCAGGAC CGAGAGCCCTAAATAAGTCACACAGCACCCTGAAAGTGATTCCCTGGTCTACTTGAA TTTGACACAAGAGAAAAGCAGGAGGAAAAGGGGCCATTCTCCAAAGGACCTGAAAGA GCAAAAGAGGTGGGAGCGAAAGCCTTAAGGATCCCACGACTTTTTACTGCCATCTGA GCTACTCAGTGTTTGAATCCCAAGAGGAAGTCAGTTTACCTCTCAGGTCTGTTGTAG GACTTGATTTTGTAAAGCAATGCCATGTTATGTGGTTGAAAGGGCACTGGACTTAGT TAGTATCAGGAGCACTGAGCTCACAGACTGACTTGGGCTCCTACTGGTGGGGACCTC TGTTAGTCACTTTACCTCATCCAAAGTATAAAGGAATTGGACCAAATAATTTACCAC ATAGCTCTAAAACTTAATTTAAAATGTAATTCCAGAAAAAAAAAGGGAATAAGCAAA GGGGGAAGAATTGAAAGAGAGAGAGAAGAAAGAATACAGAGAGCTTACCTTTTGCCT TTCTGTTGATGTTACATCTCTTCTTCCTATGTTCTTAGGTCTATGAGTCTGTTTCCC CATCATTTGGTATCTAGTCCAGTTCCTGCTTACTGCTTTGCTAATAGCTGGCCTTGC TAGAATCCTTGGTTTCACTGCTGTTCTTCATGTGCTTCTATGAGATTTACTCCAACA CAAATAGGACTGAATTTATTGTGAAGTAACATTGGCAATCTTAACTTATTCATTTAA CTTATTTTTATAGCTAGATAAATATTGTTAGTCTTAGACAATAGCTCACATTTTTTG AGAAGCATGCCCTCCCTGTCCATTTGTCTTATAACATGACCCAGCCCTATTTTACGT CATTCTAAATTCAGCCTCATATAATGAAAATACATTATGAAAACAGATGTTTAGGAG ATTTCCTGTATAGCAGTCAGCCAATTCATATGCTTTGTCTCTGCTGGCTTCTTTTTC CATGCGTTAACTTTTCCCAATAGCAGAGGAGGCAAATATGAGCATACAATCCCTTTG TTCTAAAGATATTGTTCCAGCTAGTGGAATGATGTTGAATCTTTAATAACCATAATT AGTTGCTTTTTCAGTATCTTCTGCTTTGTCTGTGTCTATCCAGTGGCCTAGGAATTA AAGTGTAAGTTGTTTTCGCTGTTAAATTGGATATTTATATATATATATAGCAAGATT TTCATGTGTTATTTAATTCTGTATTGTTTCTTATATTTGTAGTAAAATATTGAACAA TTAAAAGTGTTGACTCCAAA(SEQIDNO:25) >NP_005935.4OX-2membraneglycoproteinisoforma precursor[Homosapiens] MERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQ EALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITFWNITLE DEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVF WKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQT VNKGYWFSVPLLLSIVSLVILLVLISILLYWKRHRNQDREP(SEQIDNO:26) MouseOX-2 >NM_010818.3MusmusculusCD200antigen(Cd200), (CD200) transcriptvariant1,mRNA GGGCGTGGTTGGTTGGTCGTCTCTTCCTCCACACTAGAGGAGCTGTAGAGTCTGCCT GTGCAGTGGAGGGGGCTCTCTCTACGGCGAATAGTAGTGTCCCTGCTCACAGGTGTT GCGGAGATATCCTCCATCGTGGAAGAGCTCAGACCCCGAGAAGCTGGTGTCTAGCTG CGGCCCAGAGCAAGGATGGGCAGTCTGGTATTCAGGAGACCTTTCTGCCATCTCTCC ACCTACAGCCTGATTTGGGGCATGGCAGCAGTAGCGCTGAGCACAGCTCAAGTGGAA GTGGTGACCCAGGATGAAAGAAAGGCGCTGCACACAACTGCATCCTTACGATGTTCT CTAAAAACATCCCAGGAACCCTTGATTGTGACATGGCAGAAAAAGAAAGCCGTGAGC CCAGAAAACATGGTCACCTACAGCAAAACCCATGGGGTTGTAATCCAGCCTGCCTAC AAAGACAGGATAAATGTCACAGAGCTGGGACTCTGGAACTCAAGCATCACCTTCTGG AACACAACATTGGAAGATGAGGGCTGCTACATGTGTCTCTTCAACACGTTTGGTTCT CAGAAGGTCTCAGGAACAGCTTGCCTTACCCTCTATGTACAGCCCATAGTACACCTT CACTACAACTATTTTGAAGACCACCTAAACATCACTTGCTCTGCGACTGCCCGTCCA GCCCCTGCCATCTCCTGGAAGGGTACTGGGACAGGAATTGAGAATAGTACCGAGAGT CACTTCCATTCAAATGGGACTACATCTGTCACCAGCATCCTCCGGGTCAAAGACCCC AAAACTCAAGTTGGGAAGGAAGTGATCTGCCAGGTTTTATACCTGGGGAATGTGATT GACTACAAGCAGAGTCTGGACAAAGGATTTTGGTTTTCAGTTCCACTGTTGCTAAGC ATTGTTTCTCTGGTAATTCTTCTGATCTTGATCTCCATCTTACTATACTGGAAACGT CACCGAAATCAGGAGCGGGGTGAATCATCACAGGGGATGCAAAGAATGAAATAAGAG CTCTAAAGAAATTATACAGAACCCTGAACGTGTTTCCCTGGTCTACTTGAATCTGAT GTGAAAGAAAAGCAGGAGGGAAAAGGCCATTCTCCATAGGACCTAAGGAGAGCAAAA GACCAGACACGAGCCTGTGAGGGATTTGACTTTTTGCTGTTGTCCCAGGTCCTCGGT GTTTGCATTCCAAGAGGAAGTCGAGTGCCTCGGGTCTGTTGTAGGACTTGATTTTTT TTTTTTTTGTAGAGCAATGCAGTGCCATGCTGTTAGAAAGGCTCCAGACTTAGAACC ACCAGTGCCAAGCCAGCTCTCAGACCGACTAGGGCTCCCATCGGAGGAACAAATCGT AGTCAACTTACCTCACAGAGCTCTCTGGTCCTTACACAAAGTAGAAAGGAGTGGGAC CAGAAAATTGGCCATGTCTGAAATCTGATGGAATTTTTAGGAAGAAAACTGAAGAAT AAGCAAAAGAAGAAAGAACACAGAAGGGTCCAAAGAGCTTCTGAGAGTACCTTTTGC CTTTCTGTTGGTGTCCCAGCTCTGGTTTTGTTCTTAGGTCCGCCAGTGTGTTTCCCT GTTGTTTGAGTATCTAGTTGACTACCTGCTACTGTTCTGCTGATGGTTGGCCTTGCT AGAATCCCTGACTCCCCTGCCGTTCTCTATGTGCTTCTATGAGGGTTACTATGATGA AAATAGAGCAGAAGATAGTGTGAAGTAACATTGGCAACTGTAATGTGTCCATTTAAC TTATTTTTATAGCACTTAGGCAATATTGTTAGTCTTAGTGAGTAGTTCACATCTTTA CAAAAGCATGCTCTCCCTATCCATTGGGCCCACAATAACACTCTCTTTGAGGCCATT CTGAATCCTGTCTCGTGTAATGATAATATATTATGAAAACAGATACTTTAAGAATTT CCTGTACAGCAGTCAGTTGTTTATTCTCTCTCTCTCTCTCTCTCTCTCTCTCCCTCC CCCACCCCAGCTTCTTTTTCTGTGACTTTGTTTTTCATAAAGAGAAGGCATCTCCTG AATACAATCGCTTTGTTCTGAAGACATCGTGAACTATTAATTCTTAACCCTTTGACA AAACTAGTGAAGTTGTTTTCTGTATCTTTTGCTTCATCTGTCTTTATAGAGTGACCT AGGAATTCAAGTGTAAGTTGTTTCCATTGTTGAACTGGATATTTATATACTTGGTAT GCTTTTCACGTGTTATTTAATTCTGTATAATTTCCTATATTTGTATTAAAATATTGA GCAATTAAAAGTGTCAACTAAATATTTGATGTGGCATTCCCTTGAGAAATATAGAAA TAAAGAATAAAAAAAAAAAAAAAAAA(SEQIDNO:27) >NP_034948.3OX-2membraneglycoproteinisoform1 precursor[Musmusculus] MGSLVFRRPFCHLSTYSLIWGMAAVALSTAQVEVVTQDERKALHTTASLRCSLKTSQ EPLIVTWQKKKAVSPENMVTYSKTHGVVIQPAYKDRINVTELGLWNSSITFWNTTLE DEGCYMCLFNTFGSQKVSGTACLTLYVQPIVHLHYNYFEDHLNITCSATARPAPAIS WKGTGTGIENSTESHFHSNGTTSVTSILRVKDPKTQVGKEVICQVLYLGNVIDYKQS LDKGFWFSVPLLLSIVSLVILLILISILLYWKRHRNQERGESSQGMQRMK (SEQIDNO:28) Human >NM_009587.3Homosapiensgalectin9(LGALS9),transcript Galectin-9 variant1,mRNA CTTTGTTAAGTCGTTCCCTCTACAAAGGACTTCCTAGTGGGTGTGAAAGGCAGCGGT GGCCACAGAGGCGGCGGAGAGATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGT CCAGCTGTCCCCTTTTCTGGGACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATC ACTGTCAATGGGACCGTTCTCAGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAG ACTGGCTTCAGTGGAAATGACATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGA GGGTACGTGGTGTGCAACACGAGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAG ACACACATGCCTTTCCAGAAGGGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGC TCAGATTTCAAGGTGATGGTGAACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTG CCCTTCCACCGTGTGGACACCATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATC AGCTTCCAGAACCCCCGCACAGTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTC TCCCAGCCTGTCTGTTTCCCACCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGC GTGTGGCCTGCCAACCCGGCTCCCATTACCCAGACAGTCATCCACACAGTGCAGAGC GCCCCTGGACAGATGTTCTCTACTCCCGCCATCCCACCTATGATGTACCCCCACCCC GCCTATCCGATGCCTTTCATCACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCC ATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGC TCTGGGAACCACATCGCCTTCCACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTC CGCAACACCCAGATCGACAACTCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAA ATGCCCTTCGTCCGTGGCCAGAGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGC CTCAAGGTGGCCGTGGATGGTCAGCACCTGTTTGAATACTACCATCGCCTGAGGAAC CTGCCCACCATCAACAGACTGGAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAG ACATAGGCGGCTTCCTGGCCCTGGGGCCGGGGGCTGGGGTGTGGGGCAGTCTGGGTC CTCTCATCATCCCCACTTCCCAGGCCCAGCCTTTCCAACCCTGCCTGGGATCTGGGC TTTAATGCAGAGGCCATGTCCTTGTCTGGTCCTGCTTCTGGCTACAGCCACCCTGGA ACGGAGAAGGCAGCTGACGGGGATTGCCTTCCTCAGCCGCAGCAGCACCTGGGGCTC CAGCTGCTGGAATCCTACCATCCCAGGAGGCAGGCACAGCCAGGGAGAGGGGAGGAG TGGGCAGTGAAGATGAAGCCCCATGCTCAGTCCCCTCCCATCCCCCACGCAGCTCCA CCCCAGTCCCAAGCCACCAGCTGTCTGCTCCTGGTGGGAGGTGGCCTCCTCAGCCCC TCCTCTCTGACCTTTAACCTCACTCTCACCTTGCACCGTGCACCAACCCTTCACCCC TCCTGGAAAGCAGGCCTGATGGCTTCCCACTGGCCTCCACCACCTGACCAGAGTGTT CTCTTCAGAGGACTGGCTCCTTTCCCAGTGTCCTTAAAATAAAGAAATGAAAATGCT TGTTGGCACATTCA(SEQIDNO:29) >NP_033665.1galectin-9isoformlong[Homosapiens] MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGND IAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMV NGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFP PRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMESTPAIPPMMYPHPAYPMPFI TTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDN SWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRL EVGGDIQLTHVQT(SEQIDNO:30) Mouse >NM_010708.2Musmusculuslectin,galactosebinding, Galectin-9 soluble9(Lgals9),transcriptvariant1,mRNA GCCAAATAGCTGTGGTTTCTGTTTCCTAGCTCAGCCCTGCCCTGCGCAGAGTTCTGT CGTCCACCATCGAGTGAGGAAGAGAGCATTGGTTCCCCTGAGATAGAAGAGATGGCT CTCTTCAGTGCCCAGTCTCCATACATTAACCCGATCATCCCCTTTACTGGACCAATC CAAGGAGGGCTGCAGGAGGGACTTCAGGTGACCCTCCAGGGGACTACCAAGAGTTTT GCACAAAGGTTTGTGGTGAACTTTCAGAACAGCTTCAATGGAAATGACATTGCCTTC CACTTCAACCCCCGGTTTGAGGAAGGAGGGTATGTGGTTTGCAACACGAAGCAGAAC GGACAGTGGGGTCCTGAGGAGAGAAAGATGCAGATGCCCTTCCAGAAGGGGATGCCC TTTGAGCTTTGCTTCCTGGTGCAGAGGTCAGAGTTCAAGGTGATGGTGAACAAGAAA TTCTTTGTGCAGTACCAACACCGCGTACCCTACCACCTCGTGGACACCATCGCTGTC TCCGGCTGCTTGAAGCTGTCCTTTATCACCTTCCAGAACTCTGCAGCCCCTGTCCAG CATGTCTTCTCCACAGTGCAGTTCTCTCAGCCAGTCCAGTTCCCACGGACCCCTAAG GGGCGCAAACAGAAAACTCAGAACTTTCGTCCTGCCCACCAGGCACCCATGGCTCAA ACTACCATCCATATGGTTCACAGCACCCCTGGACAGATGTTCTCTACTCCTGGAATC CCTCCTGTGGTGTACCCCACCCCAGCCTATACCATACCTTTCTACACCCCCATTCCA AATGGGCTTTACCCGTCCAAGTCCATCATGATATCAGGCAATGTCTTGCCAGATGCT ACGAGGTTCCATATCAACCTTCGCTGTGGAGGTGACATTGCTTTCCACCTGAACCCC CGTTTCAATGAGAATGCTGTTGTCCGAAACACTCAGATCAACAACTCCTGGGGGCAG GAAGAGCGAAGTCTGCTTGGGAGGATGCCCTTCAGTCGAGGCCAGAGCTTCTCGGTG TGGATCATATGTGAAGGTCACTGCTTCAAGGTAGCTGTGAATGGTCAACACATGTGT GAATATTACCACCGCCTGAAGAACTTGCAGGATATCAACACTCTAGAAGTGGCGGGT GATATCCAGCTGACCCACGTGCAGACATAGGCAAGGTCTCTGGCCTAGGGATAAGGG CTGGAGCACTCTGCCTGTGTCTTATCTTTCCCCTGTCTCAGCCCTGGCACCATCAGA AGAGATCATCACTTATAGGAATTCCAGGAAGGTGAAATTCCCAATTGACTCCCTCCA CAAAGGGGGTTTTCTAGGCTGTGTGGCACATGGCTGTCAGCCCATAGTCTGAGCCAT TGCCCCCAAGCTAGCTATATACTGAGGGAAGTGACCCTCCTGGGTTTGCTCAGATCT CTGATCGTTCCCCCCTCTGTGGCCCTTTTCTTTCACCCCTCCAGGAGAGCCACCCTG ATATCATCCCACTGGCCTCCAACTGACCCACAATGTCCACAGTAACTTTCCCCCATT CTCACCCAGTATCCATAAAATAAAGAAATAATATTGCTTGTCTACAC(SEQID NO:31) >NP_034838.2galectin-9isoform1[Musmusculus] MALFSAQSPYINPIIPFTGPIQGGLQEGLQVTLQGTTKSFAQRFVVNFQNSFNGNDI AFHFNPRFEEGGYVVCNTKQNGQWGPEERKMQMPFQKGMPFELCFLVQRSEFKVMVN KKFFVQYQHRVPYHLVDTIAVSGCLKLSFITFQNSAAPVQHVFSTVQFSQPVQFPRT PKGRKQKTQNFRPAHQAPMAQTTIHMVHSTPGQMFSTPGIPPVVYPTPAYTIPFYTP IPNGLYPSKSIMISGNVLPDATRFHINLRCGGDIAFHLNPRFNENAVVRNTQINNSW GQEERSLLGRMPFSRGQSFSVWIICEGHCFKVAVNGQHMCEYYHRLKNLQDINTLEV AGDIQLTHVQT(SEQIDNO:32) HumanPVR >NM_006505.5HomosapiensPVRcelladhesionmolecule (CD155) (PVR),transcriptvariant1,mRNA AGTCACTTGTCTGGAGCTTGAAGAAGTGGGTATTCCCCTTCCCACCCCAGGCACTGG AGGAGCGGCCCCCCGGGGATTCCAGGACCTGAGCTCCGGGAGCTGGACTCGCAGCGA CCGCGGCAGAGCGAGCGGGCGCCGGGAAGCGAGGAGACGCCCGCGGGAGGCCCAGCT GCTCGGAGCAACTGGCATGGCCCGAGCCATGGCCGCCGCGTGGCCGCTGCTGCTGGT GGCGCTACTGGTGCTGTCCTGGCCACCCCCAGGAACCGGGGACGTCGTCGTGCAGGC GCCCACCCAGGTGCCCGGCTTCTTGGGCGACTCCGTGACGCTGCCCTGCTACCTACA GGTGCCCAACATGGAGGTGACGCATGTGTCACAGCTGACTTGGGCGCGGCATGGTGA ATCTGGCAGCATGGCCGTCTTCCACCAAACGCAGGGCCCCAGCTATTCGGAGTCCAA ACGGCTGGAATTCGTGGCAGCCAGACTGGGCGCGGAGCTGCGGAATGCCTCGCTGAG GATGTTCGGGTTGCGCGTAGAGGATGAAGGCAACTACACCTGCCTGTTCGTCACGTT CCCGCAGGGCAGCAGGAGCGTGGATATCTGGCTCCGAGTGCTTGCCAAGCCCCAGAA CACAGCTGAGGTTCAGAAGGTCCAGCTCACTGGAGAGCCAGTGCCCATGGCCCGCTG CGTCTCCACAGGGGGTCGCCCGCCAGCCCAAATCACCTGGCACTCAGACCTGGGCGG GATGCCCAATACGAGCCAGGTGCCAGGGTTCCTGTCTGGCACAGTCACTGTCACCAG CCTCTGGATATTGGTGCCCTCAAGCCAGGTGGACGGCAAGAATGTGACCTGCAAGGT GGAGCACGAGAGCTTTGAGAAGCCTCAGCTGCTGACTGTGAACCTCACCGTGTACTA CCCCCCAGAGGTATCCATCTCTGGCTATGATAACAACTGGTACCTTGGCCAGAATGA GGCCACCCTGACCTGCGATGCTCGCAGCAACCCAGAGCCCACAGGCTATAATTGGAG CACGACCATGGGTCCCCTGCCACCCTTTGCTGTGGCCCAGGGCGCCCAGCTCCTGAT CCGTCCTGTGGACAAACCAATCAACACAACTTTAATCTGCAACGTCACCAATGCCCT AGGAGCTCGCCAGGCAGAACTGACCGTCCAGGTCAAAGAGGGACCTCCCAGTGAGCA CTCAGGCATGTCCCGTAACGCCATCATCTTCCTGGTTCTGGGAATCCTGGTTTTTCT GATCCTGCTGGGGATCGGGATTTATTTCTATTGGTCCAAATGTTCCCGTGAGGTCCT TTGGCACTGTCATCTGTGTCCCTCGAGTACAGAGCATGCCAGCGCCTCAGCTAATGG GCATGTCTCCTATTCAGCTGTGAGCAGAGAGAACAGCTCTTCCCAGGATCCACAGAC AGAGGGCACAAGGTGACAGCGTCGGGACTGAGAGGGGAGAGAGACTGGAGCTGGCAA GGACGTGGGCCTCCAGAGTTGGACCCGACCCCAATGGATGAAGACCCCCTCCAAAGA GACCAGCCTCCCTCCCTGTGCCAGACCTCAAAACGACGGGGGCAGGTGCAAGTTCAT AGGTCTCCAAGACCACCCTCCTTTCATTTGCTAGAAGGACTCACTAGACTCAGGAAA GCTGTTAGGCTCACAGTTACAGTTTATTACAGTAAAAGGACAGAGATTAAGATCAGC AAAGGGAGGAGGTGCACAGCACACGTTCCACGACAGATGAGGCGACGGCTTCCATCT GCCCTCTCCCAGTGGAGCCATATAGGCAGCACCTGATTCTCACAGCAACATGTGACA ACATGCAAGAAGTACTGCCAATACTGCCAACCAGAGCAGCTCACTCGAGATCTTTGT GTCCAGAGTTTTTTGTTTGTCTTGAGACAGGGTCTGGCTCTGTTGGCAGACTAGAGT ACAGTGGTGAGATCACAGTTCATTGCAGCCTTGACTTCTCAACGCCAAGTCATCCTC CCACCTCAGCCTCCTGAGTAGCTATGACTACAGGTATGTGCCACCACGTCTGGCTAA TCTTTTTATTATTTGTAAAGTCGAGGTTTCCCTGTGTTGCCCAGGCTGGTCTTGAAC TCTTGGCTCCAAGTGATACTTCTGCCTTGGCCTCCCAAAGTGCTGAATTAAGCAGCT CACCATCCACACGGCTGACCTCATACATCAAGCCAATACCGTGTGGCCCAAGACCCC CACCATAAATCACATCATTAGCATGAACCACCCAGAGTGGCCCAAGACTCCAAGATC AGCTACCAGGCAGGATATTCCAAGGGCTTAGAGATGAATGCCCAGGAGCTGAGGATA AAGGGCCCGATCTTTCTTTGGGCAAGGTTAAGCCTTTACTGCATAGCAGACCACACA GAAGGGTGTGGGCCACCAGAGAATTTTGGTAAAAATTTGGCCTCTGGCCTTGAGCTT CTAAATCTCTGTATCCGTCAGATCTCTGTGGTTACAAGAAACAGCCACTGACCCTGG TCACCAGAGGCTGCAATTCAGGCCGCAAGCAGCTGCCTGGGGGGTGTCCAAGGAGCA GAGAAAACTACTAGATGTGAACTTGAAGAAGGTTGTCAGCTGCAGCCACTTTCTGCC AGCATCTGCAGCCACTTTCTGCCAGCATCTGCAGCCAGCAAGCTGGGACTGGCAGGA AATAACCCACAAAAGAAGCAAATGCAATTTCCAACACAAGGGGGAAGGGATGCAGGG GGAGGCAGCGCTGCAGTTGCTCAGGACACGCTCCTATAGGACCAAGATGGATGCGAC CCAAGACCCAGGAGGCCCAGCTGCTCAGTGCAACTGACAAGTTAAAAAGGTCTATGA TCTTGAGGGCAGACAGCAGAATTCCTCTTATAAAGAAAACTGTTTGGGAAAATACGT TGAGGGAGAGAAGACCTTGGGCCAAGATGCTAAATGGGAATGCAAAGCTTGAGCTGC TCTGCAAGAGAAAATAAGCAGGACAGAGGATTTGCTCTGGACAGAGATGGAAGAGCC GGGAACAGAGAAGTGTGGGGAAGAGATAGGAACCAGCAGGATGGCAGGGGCAAAGGG CTCAAGGGTGAGGAGGCCAGTGGGACCCCACAGAGTTGGGGAGATAAAGGAACATTG GTTGCTTTGGTGGCACGTAAGCTCCTTGTCTGTCTCCAGCACCCAGAATCTCATTAA AGCTTATTTATTGTACCTCCAGCGGCTGTGTGCAATGGGGTCTTTTGTGGAAATCAA GGAGCAGACAGGTTTCATGTGTACTGTCACCACGTGGGATGGAACCAGAGGCATGGA AGCAAGACGCTAAATGAAGAGGGCCATAAGGGCTGGGATTCCCAGGCACCTTAGGAA CAGCTTGTCTTTTTTTTTTTCCTCTCCAAAAAAAATGTTTAAGGGACGGTGTCTCCT GTCACCCAGGCTGGAGTGCAATGGCACGATCATAGCTCATTGCAGCCTCTAACTCCG GGGCTCAAGCAATCCTCCCACCTCAGCCTACCAAGTAGCTGTGACCACAGCTGCCCC TCACCATGCTAAGCTAATTTTTTTAATTAGATAGTACATAAACGTCCCAAAATTAGA AGATAAAAAGACATGAGGGATCCATTCTAATTTGTGTTTGGAGTGTAATGGTCCAGC TCCATTCTTCTGCACATGGATATCCAGTTTTACACAACACTGTGAATGTAATGAATG CCACTGAATCATACACTCAAAAATAGCTAAAATGGCAAATTGTCTGTTATCTCTTTT TAACCACCATTTTTGAAAATTAATTATACCAAAAAACCATTGAATAGTGCACTTTAT TTATTTATTTATTTGTTTATTTATTTATTTATTTTAGAAATAAGAGTCTCACTTTGT TGCCCAGGCTGGAGTGCAGTGGCGTGATCATGGCTCATTGCAGCCTCGACCTGCTGG GCTCGGGCTATCCTTCCATCTCAGCCTCCCGAGTAGCTGGGACTATAGGTGGGCGCC ACCCCACCTGGCTAAATCTCTTTTTAACTTTTGTAGAGATAGGCATCTCGCTATGTT GCCTAGGCTGGGCTGGAACTCCTGGGCTCAAGTGCTCCTCCTGCCTTGGCCTCCCAA AGCGCTAGGATTACAGATGTGAGCCACCGCGCCCACCCTGAACCTTACTTTTTTTGC TCAGTTTCTGGTAATTCAGAGAATGCCTCCTGAGTTGTTCTACACCCACCTCATATT CCATGGGAGGGCTGTACAGGGCTTTTTTAACGAGGCCTCTAAGGACAGGCATTTGTA TCCTTTCCAGCCTTTCACTATTACAATGTTGTAGTGAATAACTTTACACACTGTCAT TTATTTTACTTTTTTTTTTTTTTATTTTAGAGAAAGGAATCTTGCCATCTTGCCCAG GCTGGTCTCAAATTCCTGGGCCCAAACAATCCTCCCGCCTTGGCCTCCTAAAGTACT GGGATTTATAGGCATAAGCCACCGTGCCTGGCCAATGCACACTGTCATTTAGCTCAT GTTAACACCTGAGTGTAGGACACACTCCTGGAGGTGGAATTGCTGGGCCAAAGAGTA TGTTTCTTGTCATTGTGATAGATATTGACAAATGAACCCTCACAGAAGTTGTGCTGA GTTCTGTTCCCACCAGCGACGTAGGCGATGACCTTTTTCTGGAGGGAGGGGGCATCC TTGGAGTCCACAGAGCCAGGAATGGAGAGTGGGCCCAGAATTTTGGTATAGGTGTTG TATAAACTTATAGTAAGGTTAAGAAAACCGCAACTATCCTTATCAGAGACTTGGCGG GGGGCAGGGTATGATGGAGATCATAAGGAGGCTAAAACACTCCACACCCTCCCTCTG CATTGCTCCTGCACGGGAGTCGGGAATCTTTTCAGGTTGATACGATCTCACCTTGAG GAGCTGTGAGGTCCCAGAAGCCTCTGGGTTGCAGATTGCTTGGGGTGAAAATGTCTG TGCTACTGAAATCTAACTTTTTACAAAAAATTACGGGCTGGGCGCAGTGGCTCACGC CTGTAATCCCAGCACTTTGGGAGGCTGCAGCGGGTGGATCACTTGAGGTAAGGAGTT CAAGACCAGACCATAGTGAAACCGTGTCTCTACAAAAAAAATTAGCCAGGTGTGGTG GTGCATGCTTGTAATCCCAGCTACTCAGAAGGCTGAGGTGGGAGAATCCCTTGAACC CGGGAAGTGGAGGCTGGAGTAAACCATGATCGAGTTACTGCACTCCAGCCTGGGTGA CAAGAGTGAGACTCTGTCTCCAAAAAAAAAAAAAAAAAAAAAAAAACTGGATTGCCT GGCTCTACTCCGGGCACAGCATGCAGGCCCAGTTCTGCTGCTCTGCTGTTTGTTCTG CTTTCCTCCACATATTGGCATCACCCTCTGGTGCCAAGATGGCTGCTGCATTCCAGG CATCACATCCAGACTCAGACCCAGAGAAGCTGCCCATCCCTACCTGGGTGAGCCTTT GTAGGAACGAGAAACCGCATCCAGCAGCAGAAACCTCACCCAGCAGCGTCTTTTCCG GTCTCATTCACCAGCGCCGCCCACCGCTCAACCAATCCCTGGCCAAAAGAATGGGAC CGCCTGGAAGGCTGGACCAAACAGGACCTGCCCTCTGGGGCTGGGGAGAGGCCCAGA TGAAGGCTGCAGGACAGGATGGACTCCTAGACCTCTGTTACCAGCAGTGACTACCTC TGTCTGGGTGGTTGGAACATGTTTGAATTTTATTCTAAGTACTGTCTACAAGTTCTG CAATAAACCTTGACTCTTCTTTTAATAATGCAAAA(SEQIDNO:33) >NP_006496.4poliovirusreceptorisoformalphaprecursor [Homosapiens] MARAMAAAWPLLLVALLVLSWPPPGTGDVVVQAPTQVPGFLGDSVTLPCYLQVPNME VTHVSQLTWARHGESGSMAVFHQTQGPSYSESKRLEFVAARLGAELRNASLRMFGLR VEDEGNYTCLFVTFPQGSRSVDIWLRVLAKPQNTAEVQKVQLTGEPVPMARCVSTGG RPPAQITWHSDLGGMPNTSQVPGFLSGTVTVTSLWILVPSSQVDGKNVTCKVEHESF EKPQLLTVNLTVYYPPEVSISGYDNNWYLGQNEATLTCDARSNPEPTGYNWSTTMGP LPPFAVAQGAQLLIRPVDKPINTTLICNVTNALGARQAELTVQVKEGPPSEHSGMSR NAIIFLVLGILVFLILLGIGIYFYWSKCSREVLWHCHLCPSSTEHASASANGHVSYS AVSRENSSSQDPQTEGTR(SEQIDNO:34) MousePVR >NM_027514.2Musmusculuspoliovirusreceptor(Pvr),mRNA (CD155) AGGCGGCACCCGCTTAGCTGAGATTCCAGCACTTGACTTCAGGGTTTCGGAGAGATA AGGCGCTTGGCCGTTACTAACTGGACTACAAAGAGCTGGATCGGACCGGAACCACAT GGCTCAACTCGCCCGAGCCACCCGCTCCCCGCTGTCATGGCTGCTGCTGCTGTTCTG CTATGCACTCCGGAAAGCGGGTGGGGATATACGTGTGCTGGTGCCCTACAATTCGAC AGGCGTCTTGGGAGGGTCGACCACCTTGCACTGTAGTCTGACTTCTAATGAGAATGT GACTATCACTCAAATAACCTGGATGAAGAAGGATTCAGGTGGATCCCACGCTCTTGT GGCTGTCTTCCACCCCAAGAAGGGGCCCAACATCAAAGAGCCAGAGAGGGTGAAATT CTTGGCTGCCCAACAGGATCTGAGGAACGCATCTCTGGCCATCTCGAACTTAAGTGT AGAAGACGAAGGCATCTATGAATGTCAGATTGCCACATTCCCCAGAGGCAGTAGAAG CACCAATGCCTGGCTGAAGGTGCAAGCCCGACCTAAGAACACTGCAGAGGCCCTGGA GCCCTCTCCCACCTTGATACTGCAGGATGTGGCTAAATGCATCTCTGCCAATGGTCA CCCTCCTGGACGAATCTCTTGGCCCTCGAATGTGAATGGAAGTCACCGTGAAATGAA GGAACCAGGGTCCCAGCCGGGCACCACCACAGTTACCAGCTACCTCTCCATGGTACC TTCTCGCCAGGCAGACGGCAAGAACATCACCTGCACGGTGGAGCATGAAAGCTTACA GGAGCTGGACCAGCTGCTGGTGACCCTTTCCCAACCCTATCCACCTGAAAACGTGTC CATCTCTGGCTATGACGGCAACTGGTATGTTGGCCTCACTAACTTGACCCTGACCTG TGAAGCTCACAGCAAACCAGCGCCTGACATGGCTGGATATAACTGGAGCACGAACAC GGGTGACTTTCCCAACTCTGTTAAGCGCCAGGGCAATATGCTTCTAATCTCCACCGT AGAGGATGGTCTCAATAACACGGTCATTGTGTGCGAAGTCACCAATGCCCTAGGGTC TGGGCAGGGCCAAGTGCACATCATTGTTAAAGAGAAACCTGAGAATATGCAGCAAAA TACAAGATTACACCTAGGCTACATCTTTCTTATCGTCTTTGTCCTCGCTGTAGTCAT CATCATCGCAGCACTATACACTATACGAAGATGCAGGCATGGTCGTGCTCTGCAGTC CAATCCCTCAGAGAGGGAGAACGTCCAGTATTCATCTGTGAACGGCGACTGTAGACT GAACATGGAGCCAAACAGCACAAGGTGACGGTGCTGGGTAGACAGAACTAAGGAACT TGAAGGCATAGCAACTGGAACCCTACTCTCATAAATGAAGAAGCCTCCAGAGAGACT GGCTGCTCAGTGTGATGAGCATAGCAAGTTTGGGGGGTCTCCCAGGATGCTGCCGAA TTCCACGTTGTCAAAAGGACCCATGGAGGCCAGTGTGTTGGCTCACTCTTGACATCT CAGCAAGCTGGGGGGGGGGGGGGGAGCATAAAGCAAGGTTGAGTCTAGCTTGGGCTA TAGAGCAAAGCCCTGTCCATACACAAACAAGCTAAGGGGCTTTGAGACGGTCAGAAA CTGAAGTCTTGCTTTGGGTAAGGTAAATCCTCTACCGCATGTATGTGCTAGACTTGA AAGACTTCCACACAGACCTCTTTATAAGTTGACTCCATTGGGGCTATCCCCTCCTCT CTGGACAAGGTCTCTGTATGTAGCCAAGGCTAGGCTCAAACTCACAGAGATATGTCT GCTTCTACCTCCCCAGTGCTAGAGTTGAAAGTATTTGTGCCACTGCACTTTTCTAGG TCTTCTTTTAATGAAGTAAAGTATATATTTATAAAAAGCTATTTAGTTATATATATA TATATTTTTGAGACTATTTCATAGAGCCCAAGCTAACCTCAAACTTACTATGTAGCC AAGAGTGATGGTAAACTAATTTATTTTAATTTATTTGTCTTCAATTTTAACCATCAC CCAACCCCTGCTCCCTTCCATATCTTCTTTCAATCCATTTCATTGTCTTTTTCTTCC CAGACACTATTCTGACTTACGTCTCCATTACAAACATTTTATTGAACTACATAAAAA TGTGTGAACCACAAAAAAAAAATGTATTTGTCAAAATTGTAGTTGTCTTTCTGAGGC TGACCTGAGTTCTCTGATACCATTCTCTCCAGTTGTATCCAGTTTCCTGTAAACAAT GTGACTTTGTTTTTCTCAGTAGCTAAAACATCCCAATTATGTGAGTGTACACTTTCT TTACTCATTCCTCTGTGGGCCACCAGCTGGGTTGGTTCCATATCTGAGCTATTGTGC ATGGAATTGTCTCTGTGGTGGGTTTAGTAAACTCCCAGGAATGCCTGTACATGTTTG TAGAGGCCAGAAGAAGGCACAAAATCTTGAGCCAGGCTTACATGCACTTGTGAGTAG CCCCACATAGGTGCTAAGAACCCAGTTCAGGTCCTCTGCTGTGGGATGGTGGGCTGT GCACAGAAAGCCTGGTCCCGGTCTAGCAAAGGTCTGGAACTCCGGAGCCGGTGGGCT GTGATTTACACCAGCATGGGATGGAAGGAGTTGGACCTCGCCTCCTGGGCACCTGGC TCCTGTCACATAGCTACAGCCTCCCACAGCCCCCCTATAGGGAGGTATGCAGCATCA ATCACATAGTAGCTGCACTAAGCCCTCCCACATGCAAATAAGGTTTCCCCAAACTCT CAGTCCAAGCCAATGAAAAGTACCTGCTGTCAAACCCTAAATCATCCCCAAAACTCT GTAAGTCCTATCAGGGAATAAAATGTGTGTGAAAACTAAAAAAAAAAAAAAA(SEQ IDNO:35) >NP_081790.1poliovirusreceptorprecursor[Musmusculus] MAQLARATRSPLSWLLLLFCYALRKAGGDIRVLVPYNSTGVLGGSTTLHCSLTSNEN VTITQITWMKKDSGGSHALVAVFHPKKGPNIKEPERVKFLAAQQDLRNASLAISNLS VEDEGIYECQIATFPRGSRSTNAWLKVQARPKNTAEALEPSPTLILQDVAKCISANG HPPGRISWPSNVNGSHREMKEPGSQPGTTTVTSYLSMVPSRQADGKNITCTVEHESL QELDQLLVTLSQPYPPENVSISGYDGNWYVGLTNLTLTCEAHSKPAPDMAGYNWSTN TGDFPNSVKRQGNMLLISTVEDGLNNTVIVCEVTNALGSGQGQVHIIVKEKPENMQQ NTRLHLGYIFLIVFVLAVVIIIAALYTIRRCRHGRALQSNPSERENVQYSSVNGDCR LNMEPNSTR(SEQIDNO:36) Human >NM_002856.3Homosapiensnectincelladhesionmolecule2 Nectin-2 (NECTIN2),transcriptvariantalpha,mRNA (CD112) GTGACGTCAGCGGGTTCGAACCGCCGGAGCTGAGCGAGAGGCCGGGGGTGCCGAGCC isoformalpha GGGCGGGGAGAGCTGGGCCGGGAGAGCAGAACAGGGAGGCTAGAGCGCAGCGGGAAC CGGCCCGGAGCCGGAGCCGGAGCCCCACAGGCACCTACTAAACCGCCCAGCCGATCG GCCCCCACAGAGTGGCCCGCGGGCCTCCGGCCGGGCCCAGTCCCCTCCCGGGCCCTC CATGGCCCGGGCCGCTGCCCTCCTGCCGTCGAGATCGCCGCCGACGCCGCTGCTGTG GCCGCTGCTGCTGCTGCTGCTCCTGGAAACCGGAGCCCAGGATGTGCGAGTTCAAGT GCTACCCGAGGTGCGAGGCCAGCTCGGGGGCACCGTGGAGCTGCCGTGCCACCTGCT GCCACCTGTTCCTGGACTGTACATCTCCCTGGTGACCTGGCAGCGCCCAGATGCACC TGCGAACCACCAGAATGTGGCCGCCTTCCACCCTAAGATGGGTCCCAGCTTCCCCAG CCCGAAGCCTGGCAGCGAGCGGCTGTCCTTCGTCTCTGCCAAGCAGAGCACTGGGCA AGACACAGAGGCAGAGCTCCAGGACGCCACGCTGGCCCTCCACGGGCTCACGGTGGA GGACGAGGGCAACTACACTTGCGAGTTTGCCACCTTCCCCAAGGGGTCCGTCCGAGG GATGACCTGGCTCAGAGTCATAGCCAAGCCCAAGAACCAAGCTGAGGCCCAGAAGGT CACGTTCAGCCAGGACCCTACGACAGTGGCCCTCTGCATCTCCAAAGAGGGCCGCCC ACCTGCCCGGATCTCCTGGCTCTCATCCCTGGACTGGGAAGCCAAAGAGACTCAGGT GTCAGGGACCCTGGCCGGAACTGTCACTGTCACCAGCCGCTTCACCTTGGTGCCCTC GGGCCGAGCAGATGGTGTCACGGTCACCTGCAAAGTGGAGCATGAGAGCTTCGAGGA ACCAGCCCTGATACCTGTGACCCTCTCTGTACGCTACCCTCCTGAAGTGTCCATCTC CGGCTATGATGACAACTGGTACCTCGGCCGTACTGATGCCACCCTGAGCTGTGACGT CCGCAGCAACCCAGAGCCCACGGGCTATGACTGGAGCACGACCTCAGGCACCTTCCC GACCTCCGCAGTGGCCCAGGGCTCCCAGCTGGTCATCCACGCAGTGGACAGTCTGTT CAATACCACCTTCGTCTGCACAGTCACCAATGCCGTGGGCATGGGCCGCGCTGAGCA GGTCATCTTTGTCCGAGAAACCCCCAGGGCCTCGCCCCGAGATGTGGGCCCGCTGGT GTGGGGGGCCGTGGGGGGGACACTGCTGGTGCTGCTGCTTCTGGCTGGGGGGTCCTT GGCCTTCATCCTGCTGAGGGTGAGGAGGAGGAGGAAGAGCCCTGGAGGAGCAGGAGG AGGAGCCAGTGGCGACGGGGGATTCTACGATCCGAAAGCTCAGGTGTTGGGAAATGG GGACCCCGTCTTCTGGACACCAGTAGTCCCTGGTCCCATGGAACCAGATGGCAAGGA TGAGGAGGAGGAGGAGGAGGAAGAGAAGGCAGAGAAAGGCCTCATGTTGCCTCCACC CCCAGCACTCGAGGATGACATGGAGTCCCAGCTGGACGGCTCCCTCATCTCACGGCG GGCAGTTTATGTGTGACCTGGACACAGACAGAGACAGAGCCAGGCCCGGCCCTCCCG CCCCCGACCTGACCACGCCGGCCTAGGGTTCCAGACTGGTTGGACTTGTTCGTCTGG ACGACACTGGAGTGGAACACTGCCTCCCACTTTCTTGGGACTTGGAGGGAGGTGGAA CAGCACACTGGACTTCTCCCGTCTCTAGGGCTGCATGGGGAGCCCGGGGAGCTGAGT AGTGGGGATCCAGAGAGGACCCCCGCCCCCAGAGACTTGGTTTTGGCTCCAGCCTTC CCCTGGCCCCGTGACACTCAGGAGTTAATAAATGCCTTGGAGGAAAACA(SEQID NO:37) >NP_002847.1nectin-2isoformalphaprecursor[Homo sapiens] MARAAALLPSRSPPTPLLWPLLLLLLLETGAQDVRVQVLPEVRGQLGGTVELPCHLL PPVPGLYISLVTWQRPDAPANHQNVAAFHPKMGPSFPSPKPGSERLSFVSAKQSTGQ DTEAELQDATLALHGLTVEDEGNYTCEFATFPKGSVRGMTWLRVIAKPKNQAEAQKV TFSQDPTTVALCISKEGRPPARISWLSSLDWEAKETQVSGTLAGTVTVTSRFTLVPS GRADGVTVTCKVEHESFEEPALIPVTLSVRYPPEVSISGYDDNWYLGRTDATLSCDV RSNPEPTGYDWSTTSGTFPTSAVAQGSQLVIHAVDSLFNTTFVCTVTNAVGMGRAEQ VIFVRETPRASPRDVGPLVWGAVGGTLLVLLLLAGGSLAFILLRVRRRRKSPGGAGG GASGDGGFYDPKAQVLGNGDPVFWTPVVPGPMEPDGKDEEEEEEEEKAEKGLMLPPP PALEDDMESQLDGSLISRRAVYV(SEQIDNO:38) MouseNectin- >NM_001159724.1Musmusculusnectincelladhesion 2(CD112) molecule2(Nectin2),transcriptvariant2,mRNA isoformalpha GAGCCCTAGGATCGGCTTGGCGAAGAGGGGCGGGGCCTGTGACGTCATGAGTCCGGC CCGCTGGAGCTAAGCGAGGGGCCGGGGGGCGCGGATCCTGAGAGCCAGGCGAGGGAA AGCTGGGCCGAACGAACTGATCCGGGGAGCCGTGAGCGGCGGAAGCCGGCCTGGAGC CGGACACTTCAGACCCCTGACTGCCCTCCCAGCCGATCGGTACACGAAGAGTGGTCC CTAGGCACCCCCTGCCCGGGCCCAGTCCCTCCCCGGGCCCCCCATGGCCCGGGCCGC AGTCCTCCCGCCGTCCAGATTGTCACCGACGCTGCCGTTGTTGCCGCTGCTACTGCT CCTGCTTCAGGAAACAGGAGCCCAAGATGTGCGGGTACGAGTGCTTCCCGAGGTCCG GGGCCGCTTGGGAGGCACCGTGGAGTTACCGTGCCACCTGCTCCCACCCACGACGGA GCGCGTCTCTCAGGTGACCTGGCAGCGCCTGGATGGCACAGTTGTGGCTGCTTTCCA CCCATCCTTCGGAGTGGATTTCCCCAACTCTCAGTTCAGCAAGGACCGTCTGTCCTT TGTCAGAGCGAGACCAGAAACAAACGCAGACCTGCGGGATGCCACACTGGCCTTCCG GGGACTGAGGGTAGAGGACGAGGGCAATTACACCTGCGAGTTTGCCACGTTTCCCAA CGGTACCCGCAGGGGGGTGACCTGGCTCAGAGTCATAGCCCAGCCTGAGAACCACGC TGAAGCCCAGGAGGTCACAATTGGCCCCCAGTCGGTGGCTGTAGCCCGCTGTGTCTC CACTGGGGGCCGCCCCCCTGCCCGAATCACCTGGATCTCATCTCTGGGTGGAGAGGC CAAAGATACTCAGGAGCCAGGGATACAGGCTGGCACCGTCACTATCATCAGCCGATA CTCCTTGGTGCCCGTGGGCCGAGCGGATGGCGTCAAGGTCACGTGTAGAGTGGAACA CGAGAGCTTCGAAGAGCCGATCCTGCTGCCAGTGACCCTCTCTGTGCGCTACCCTCC AGAAGTATCCATCTCCGGCTATGATGACAACTGGTACCTTGGCCGCAGTGAGGCCAT ACTGACCTGTGATGTACGAAGCAACCCAGAGCCCACAGACTATGACTGGAGCACGAC CTCGGGCGTCTTCCCAGCCTCTGCAGTGGCCCAGGGCTCTCAGCTGCTTGTCCACTC TGTGGATCGAATGGTCAACACTACCTTCATCTGTACAGCCACCAACGCTGTGGGGAC AGGCCGTGCTGAGCAGGTCATCCTGGTGCGAGACACCCCCCAGGCCTCCCGAGATGT GGGTCCGCTGGTGTGGGGGGCCGTGGGGGGAACATTGCTGGTGCTACTCCTGGCTGG GGGGTTCCTGGCCTTGATCCTGCTGAGGGGGAGGAGGAGGCGGAAGAGCCCTGGAGG AGGAGGAAATGATGGCGACAGAGGATCCTACGATCCAAAGACTCAGGTGTTTGGGAA CGGGGGTCCTGTCTTCTGGAGGTCAGCATCCCCTGAGCCCATGAGGCCAGATGGCAG GGAGGAAGATGAGGAGGAGGAGGAAGAAATGAAGGCAGAGGAAGGTCTCATGCTACC TCCACACGAGTCACCTAAGGACGACATGGAGTCCCATCTGGATGGCTCCCTCATCTC TCGGCGGGCAGTTTACGTGTGACCCTACGATATAGACACTGGACACATGGAAACACC AAGTTCCACCCTCACTGCCAACCACACCAATGCCAGCCAGCAACGATGGCTAGGGAC CGGTTGGACTGGTTCTTCTGGGGCACACTGGAGTTGGAAGGGCACCGCCCCTGCTTT CAGGATAGAGGACAAGTGGAACCACACAGACTCCTATCTTTAGGGCCTCATGGAGTA GGGGACCCCAGGAGCGCCATGGTGCACACTCAGGACTCCTCAGAGCTTGCTTTCGGC CCCAGCCTAGCCCTGGCCCCGAAACACTCAGGAGCTAATAAATGCCTTGTCGGAAAA AAAAAAAAAAAAAA(SEQIDNO:39) >NP_001153196.1nectin-2isoform2precursor[Mus musculus] MARAAVLPPSRLSPTLPLLPLLLLLLQETGAQDVRVRVLPEVRGRLGGTVELPCHLL PPTTERVSQVTWQRLDGTVVAAFHPSFGVDFPNSQFSKDRLSFVRARPETNADLRDA TLAFRGLRVEDEGNYTCEFATFPNGTRRGVTWLRVIAQPENHAEAQEVTIGPQSVAV ARCVSTGGRPPARITWISSLGGEAKDTQEPGIQAGTVTIISRYSLVPVGRADGVKVT CRVEHESFEEPILLPVTLSVRYPPEVSISGYDDNWYLGRSEAILTCDVRSNPEPTDY DWSTTSGVFPASAVAQGSQLLVHSVDRMVNTTFICTATNAVGTGRAEQVILVRDTPQ ASRDVGPLVWGAVGGTLLVLLLAGGFLALILLRGRRRRKSPGGGGNDGDRGSYDPKT QVFGNGGPVFWRSASPEPMRPDGREEDEEEEEEMKAEEGLMLPPHESPKDDMESHLD GSLISRRAVYV(SEQIDNO:40) Human >NM_001042724.2Homosapiensnectincelladhesion Nectin-2 molecule2(NECTIN2),transcriptvariantdelta,mRNA (CD112) GTGACGTCAGCGGGTTCGAACCGCCGGAGCTGAGCGAGAGGCCGGGGGTGCCGAGCC isoformdelta GGGCGGGGAGAGCTGGGCCGGGAGAGCAGAACAGGGAGGCTAGAGCGCAGCGGGAAC CGGCCCGGAGCCGGAGCCGGAGCCCCACAGGCACCTACTAAACCGCCCAGCCGATCG GCCCCCACAGAGTGGCCCGCGGGCCTCCGGCCGGGCCCAGTCCCCTCCCGGGCCCTC CATGGCCCGGGCCGCTGCCCTCCTGCCGTCGAGATCGCCGCCGACGCCGCTGCTGTG GCCGCTGCTGCTGCTGCTGCTCCTGGAAACCGGAGCCCAGGATGTGCGAGTTCAAGT GCTACCCGAGGTGCGAGGCCAGCTCGGGGGCACCGTGGAGCTGCCGTGCCACCTGCT GCCACCTGTTCCTGGACTGTACATCTCCCTGGTGACCTGGCAGCGCCCAGATGCACC TGCGAACCACCAGAATGTGGCCGCCTTCCACCCTAAGATGGGTCCCAGCTTCCCCAG CCCGAAGCCTGGCAGCGAGCGGCTGTCCTTCGTCTCTGCCAAGCAGAGCACTGGGCA AGACACAGAGGCAGAGCTCCAGGACGCCACGCTGGCCCTCCACGGGCTCACGGTGGA GGACGAGGGCAACTACACTTGCGAGTTTGCCACCTTCCCCAAGGGGTCCGTCCGAGG GATGACCTGGCTCAGAGTCATAGCCAAGCCCAAGAACCAAGCTGAGGCCCAGAAGGT CACGTTCAGCCAGGACCCTACGACAGTGGCCCTCTGCATCTCCAAAGAGGGCCGCCC ACCTGCCCGGATCTCCTGGCTCTCATCCCTGGACTGGGAAGCCAAAGAGACTCAGGT GTCAGGGACCCTGGCCGGAACTGTCACTGTCACCAGCCGCTTCACCTTGGTGCCCTC GGGCCGAGCAGATGGTGTCACGGTCACCTGCAAAGTGGAGCATGAGAGCTTCGAGGA ACCAGCCCTGATACCTGTGACCCTCTCTGTACGCTACCCTCCTGAAGTGTCCATCTC CGGCTATGATGACAACTGGTACCTCGGCCGTACTGATGCCACCCTGAGCTGTGACGT CCGCAGCAACCCAGAGCCCACGGGCTATGACTGGAGCACGACCTCAGGCACCTTCCC GACCTCCGCAGTGGCCCAGGGCTCCCAGCTGGTCATCCACGCAGTGGACAGTCTGTT CAATACCACCTTCGTCTGCACAGTCACCAATGCCGTGGGCATGGGCCGCGCTGAGCA GGTCATCTTTGTCCGAGAGACCCCCAACACAGCAGGCGCAGGGGCCACAGGCGGCAT CATCGGGGGCATCATCGCCGCCATCATTGCTACTGCTGTGGCTGCCACGGGCATCCT TATCTGCCGGCAGCAGCGGAAGGAGCAGACGCTGCAGGGGGCAGAGGAGGACGAAGA CCTGGAGGGACCTCCCTCCTACAAGCCACCGACCCCAAAAGCGAAGCTGGAGGCACA GGAGATGCCCTCCCAGCTCTTCACTCTGGGGGCCTCGGAGCACAGCCCACTCAAGAC CCCCTACTTTGATGCTGGCGCCTCATGCACTGAGCAGGAAATGCCTCGATACCATGA GCTGCCCACCTTGGAAGAACGGTCAGGACCCTTGCACCCTGGAGCCACAAGCCTGGG GTCCCCCATCCCGGTGCCTCCAGGGCCACCTGCTGTGGAAGACGTTTCCCTGGATCT AGAGGATGAGGAGGGGGAGGAGGAGGAAGAGTATCTGGACAAGATCAACCCCATCTA TGATGCTCTGTCCTATAGCAGCCCCTCTGATTCCTACCAGGGCAAAGGCTTTGTCAT GTCCCGGGCCATGTATGTGTGAGCTGCCATGCGCCTGGCGTCTCACATCTCACCTGT TGATCCCTTAGCTTTCTTGCCAAGGATCTAGTGCCCCCTGACCTCTGGCCAGGCCAC TGTCAGTTAACACATATGCATTCCATTTGTGATGTCTACCTTGGTGGCTCCACTATG ACCCCTAACCCATGAGCCCAGAGAAATTCACCGTGATAATGGAATCCTGGCAACCTT ATCTCATGAGGCAGGAGGTGGGGAAGGTGCTTCTGCACAACCTCTGATCCCAAGGAC TCCTCTCCCAGACTGTGACCTTAGACCATACCTCTCACCCCCCAATGCCTCGACTCC CCCAAAATCACAAAGAAGACCCTAGACCTATAATTTGTCTTCAGGTAGTAAATTCCC AATAGGTCTGCTGGAGTGGGCGCTGAGGGCTCCCTGCTGCTCAGACCTGAGCCCTCC AGGCAGCAGGGTCCCACTTACCCCCTCCCCACCCTGTTCCCCAAAGGTGGGAAAGAG GGGATTCCCCAGCCCAAGGCAGGGTTTTCCCAGCACCCTCCTGTAAGCAGAAGTCTC AGGGTCCAGACCCTTCCCTGAGCCCCCACCCCCACCCCAATTCCTGCCTACCAAGCA AGCAGCCCCAGCCTAGGGTCAGACAGGGTGAGCCTCATACAGACTGTGCCTTGATGG CCCCAGCCTTGGGAGAAGAATTTACTGTTAACCTGGAAGACTACTGAATCATTTTAC CCTTGCCCAGTGGAATAGGACCTAAACATCCCCCTTCCGGGGAAAGTGGGTCATCTG AATTGGGGGTAGCAATTGATACTGTTTTGTAAACTACATTTCCTACAAAATATGAAT TTATACTTTGA(SEQIDNO:41) >NP_001036189.1nectin-2isoformdeltaprecursor[Homo sapiens] MARAAALLPSRSPPTPLLWPLLLLLLLETGAQDVRVQVLPEVRGQLGGTVELPCHLL PPVPGLYISLVTWQRPDAPANHQNVAAFHPKMGPSFPSPKPGSERLSFVSAKQSTGQ DTEAELQDATLALHGLTVEDEGNYTCEFATFPKGSVRGMTWLRVIAKPKNQAEAQKV TFSQDPTTVALCISKEGRPPARISWLSSLDWEAKETQVSGTLAGTVTVTSRFTLVPS GRADGVTVTCKVEHESFEEPALIPVTLSVRYPPEVSISGYDDNWYLGRTDATLSCDV RSNPEPTGYDWSTTSGTFPTSAVAQGSQLVIHAVDSLFNTTFVCTVTNAVGMGRAEQ VIFVRETPNTAGAGATGGIIGGIIAAIIATAVAATGILICRQQRKEQTLQGAEEDED LEGPPSYKPPTPKAKLEAQEMPSQLFTLGASEHSPLKTPYFDAGASCTEQEMPRYHE LPTLEERSGPLHPGATSLGSPIPVPPGPPAVEDVSLDLEDEEGEEEEEYLDKINPIY DALSYSSPSDSYQGKGFVMSRAMYV(SEQIDNO:42) MouseNectin- >NM_008990.3Musmusculusnectincelladhesionmolecule 2(CD112) 2(Nectin2),transcriptvariant1,mRNA isoformbeta GAGCCCTAGGATCGGCTTGGCGAAGAGGGGCGGGGCCTGTGACGTCATGAGTCCGGC CCGCTGGAGCTAAGCGAGGGGCCGGGGGGCGCGGATCCTGAGAGCCAGGCGAGGGAA AGCTGGGCCGAACGAACTGATCCGGGGAGCCGTGAGCGGCGGAAGCCGGCCTGGAGC CGGACACTTCAGACCCCTGACTGCCCTCCCAGCCGATCGGTACACGAAGAGTGGTCC CTAGGCACCCCCTGCCCGGGCCCAGTCCCTCCCCGGGCCCCCCATGGCCCGGGCCGC AGTCCTCCCGCCGTCCAGATTGTCACCGACGCTGCCGTTGTTGCCGCTGCTACTGCT CCTGCTTCAGGAAACAGGAGCCCAAGATGTGCGGGTACGAGTGCTTCCCGAGGTCCG GGGCCGCTTGGGAGGCACCGTGGAGTTACCGTGCCACCTGCTCCCACCCACGACGGA GCGCGTCTCTCAGGTGACCTGGCAGCGCCTGGATGGCACAGTTGTGGCTGCTTTCCA CCCATCCTTCGGAGTGGATTTCCCCAACTCTCAGTTCAGCAAGGACCGTCTGTCCTT TGTCAGAGCGAGACCAGAAACAAACGCAGACCTGCGGGATGCCACACTGGCCTTCCG GGGACTGAGGGTAGAGGACGAGGGCAATTACACCTGCGAGTTTGCCACGTTTCCCAA CGGTACCCGCAGGGGGGTGACCTGGCTCAGAGTCATAGCCCAGCCTGAGAACCACGC TGAAGCCCAGGAGGTCACAATTGGCCCCCAGTCGGTGGCTGTAGCCCGCTGTGTCTC CACTGGGGGCCGCCCCCCTGCCCGAATCACCTGGATCTCATCTCTGGGTGGAGAGGC CAAAGATACTCAGGAGCCAGGGATACAGGCTGGCACCGTCACTATCATCAGCCGATA CTCCTTGGTGCCCGTGGGCCGAGCGGATGGCGTCAAGGTCACGTGTAGAGTGGAACA CGAGAGCTTCGAAGAGCCGATCCTGCTGCCAGTGACCCTCTCTGTGCGCTACCCTCC AGAAGTATCCATCTCCGGCTATGATGACAACTGGTACCTTGGCCGCAGTGAGGCCAT ACTGACCTGTGATGTACGAAGCAACCCAGAGCCCACAGACTATGACTGGAGCACGAC CTCGGGCGTCTTCCCAGCCTCTGCAGTGGCCCAGGGCTCTCAGCTGCTTGTCCACTC TGTGGATCGAATGGTCAACACTACCTTCATCTGTACAGCCACCAACGCTGTGGGGAC AGGCCGTGCTGAGCAGGTCATCCTGGTGCGAGAGTCACCCAGCACAGCAGGAGCAGG GGCCACTGGTGGCATCATTGGAGGTATTATCGCTGCCATCATCGCCACCGCAGTGGC TGGCACAGGCATCCTCATCTGCCGACAACAGCGGAAGGAGCAGAGGCTTCAAGCTGC GGATGAGGAAGAAGAACTGGAAGGACCTCCCTCCTATAAACCACCCACCCCGAAGGC CAAGCTGGAGGAACCAGAGATGCCCTCTCAACTCTTCACCTTGGGGGCCTCAGAGCA CAGCCCAGTGAAGACGCCATACTTTGATGCTGGTGTCTCTTGTGCTGATCAGGAGAT GCCTCGGTATCACGAGCTGCCCACTCTGGAAGAGCGGTCAGGGCCCCTGCTGTTGGG GGCTACAGGCCTGGGACCTTCTCTTCTGGTGCCTCCAGGACCCAATGTTGTGGAGGG GGTTTCCCTGAGTCTCGAAGATGAGGAGGAAGATGATGAGGAGGAAGACTTCCTGGA TAAAATCAACCCTATTTATGATGCCCTGTCCTACCCCAGCCCCTCTGACTCCTACCA GAGCAAAGACTTTTTTGTGTCACGGGCCATGTATGTGTGAGGGAGGCACAGGGGCTC TGACGTCTCACCTTTCACCCTTGACCCATGAGCTTTCCACCAGTAATCTAGGACACT CTGACTTCCAGGCAGACCAGGGACAACTATCACCCATTGCAATCCACCTGTGACTTC TTAGTGACTCCACCATGACGTCCAATCTATGATGTCTGAGGCAGGCAAACCTGCACA ACTGGAAACCTGGAGATTTTTATCTCCCTTGGCAGGGAGCTCACCATATCCTTCTGC ACCACCTGTGACCCCCCCCCCCCCCCCAAGGACTCCTAAGACTACGACCCTTTGACC ATGCCACTCAGTATCTCAAGAACCCTTAAAGTCCCAAAGGAATCGGACCTTGCACTT GTCCTCAGGCAATAGAGTCCAACAGATATGCAAGAACGGGATCAGGGGCTCCCTGTT GCTCAGACCTGAGCCCTCCAGGCAGCAGAAGCTCACCTGATCCCTCCCCACCCTGCT CCCCAAAGGTGAAAAGGAGAGGATTCCCCAATGTAAGGTAGGACCTCCCCATCTCCA CCTACTCCTGCAGGCAGGAATCTCAGGTTTCTCACACCCTCTCCTCAGCACCCAGGT TCCTGTCTCCAGAGCATGAATTCCAGGTCCAATGCTAGAGGGGAGAACCTAATGCAA GTGTGCCTTGCCACCCCAAGTTTGGGAGACTCTGCTCTTATCCTGAGGACTACTGAA TTCTTTTAACCCCTACCCAGTGAGATGAGAACTACATATCCCTCTTTAGGGGATGGT GTGTGTATGTGTGTGTGATGGAGAATCTGGGCATCTGGGTTGGGAATTTTATTTTGT AAGCATTTCCTACATAATATGAGTTTCTACTTTGATAAAGTCTTGTGTTTTCTGTG (SEQIDNO:43) >NP_033016.3nectin-2isoform1precursor[Musmusculus] MARAAVLPPSRLSPTLPLLPLLLLLLQETGAQDVRVRVLPEVRGRLGGTVELPCHLL PPTTERVSQVTWQRLDGTVVAAFHPSFGVDFPNSQFSKDRLSFVRARPETNADLRDA TLAFRGLRVEDEGNYTCEFATFPNGTRRGVTWLRVIAQPENHAEAQEVTIGPQSVAV ARCVSTGGRPPARITWISSLGGEAKDTQEPGIQAGTVTIISRYSLVPVGRADGVKVT CRVEHESFEEPILLPVTLSVRYPPEVSISGYDDNWYLGRSEAILTCDVRSNPEPTDY DWSTTSGVFPASAVAQGSQLLVHSVDRMVNTTFICTATNAVGTGRAEQVILVRESPS TAGAGATGGIIGGIIAAIIATAVAGTGILICRQQRKEQRLQAADEEEELEGPPSYKP PTPKAKLEEPEMPSQLFTLGASEHSPVKTPYFDAGVSCADQEMPRYHELPTLEERSG PLLLGATGLGPSLLVPPGPNVVEGVSLSLEDEEEDDEEEDFLDKINPIYDALSYPSP SDSYQSKDFFVSRAMYV(SEQIDNO:44) HumanIL-10 >NM_000572.3Homosapiensinterleukin10(IL10), transcriptvariant1,mRNA ACACATCAGGGGCTTGCTCTTGCAAAACCAAACCACAAGACAGACTTGCAAAAGAAG GCATGCACAGCTCAGCACTGCTCTGTTGCCTGGTCCTCCTGACTGGGGTGAGGGCCA GCCCAGGCCAGGGCACCCAGTCTGAGAACAGCTGCACCCACTTCCCAGGCAACCTGC CTAACATGCTTCGAGATCTCCGAGATGCCTTCAGCAGAGTGAAGACTTTCTTTCAAA TGAAGGATCAGCTGGACAACTTGTTGTTAAAGGAGTCCTTGCTGGAGGACTTTAAGG GTTACCTGGGTTGCCAAGCCTTGTCTGAGATGATCCAGTTTTACCTGGAGGAGGTGA TGCCCCAAGCTGAGAACCAAGACCCAGACATCAAGGCGCATGTGAACTCCCTGGGGG AGAACCTGAAGACCCTCAGGCTGAGGCTACGGCGCTGTCATCGATTTCTTCCCTGTG AAAACAAGAGCAAGGCCGTGGAGCAGGTGAAGAATGCCTTTAATAAGCTCCAAGAGA AAGGCATCTACAAAGCCATGAGTGAGTTTGACATCTTCATCAACTACATAGAAGCCT ACATGACAATGAAGATACGAAACTGAGACATCAGGGTGGCGACTCTATAGACTCTAG GACATAAATTAGAGGTCTCCAAAATCGGATCTGGGGCTCTGGGATAGCTGACCCAGC CCCTTGAGAAACCTTATTGTACCTCTCTTATAGAATATTTATTACCTCTGATACCTC AACCCCCATTTCTATTTATTTACTGAGCTTCTCTGTGAACGATTTAGAAAGAAGCCC AATATTATAATTTTTTTCAATATTTATTATTTTCACCTGTTTTTAAGCTGTTTCCAT AGGGTGACACACTATGGTATTTGAGTGTTTTAAGATAAATTATAAGTTACATAAGGG AGGAAAAAAAATGTTCTTTGGGGAGCCAACAGAAGCTTCCATTCCAAGCCTGACCAC GCTTTCTAGCTGTTGAGCTGTTTTCCCTGACCTCCCTCTAATTTATCTTGTCTCTGG GCTTGGGGCTTCCTAACTGCTACAAATACTCTTAGGAAGAGAAACCAGGGAGCCCCT TTGATGATTAATTCACCTTCCAGTGTCTCGGAGGGATTCCCCTAACCTCATTCCCCA ACCACTTCATTCTTGAAAGCTGTGGCCAGCTTGTTATTTATAACAACCTAAATTTGG TTCTAGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCTGAGG CGGGTGGATCACTTGAGGTCAGGAGTTCCTAACCAGCCTGGTCAACATGGTGAAACC CCGTCTCTACTAAAAATACAAAAATTAGCCGGGCATGGTGGCGCGCACCTGTAATCC CAGCTACTTGGGAGGCTGAGGCAAGAGAATTGCTTGAACCCAGGAGATGGAAGTTGC AGTGAGCTGATATCATGCCCCTGTACTCCAGCCTGGGTGACAGAGCAAGACTCTGTC TCAAAAAATAAAAATAAAAATAAATTTGGTTCTAATAGAACTCAGTTTTAACTAGAA TTTATTCAATTCCTCTGGGAATGTTACATTGTTTGTCTGTCTTCATAGCAGATTTTA ATTTTGAATAAATAAATGTATCTTATTCACATCA(SEQIDNO:45) >NP_000563.1interleukin-10isoform1precursor[Homo sapiens] MHSSALLCCLVLLTGVRASPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQM KDQLDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGE NLKTLRLRLRRCHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAY MTMKIRN(SEQIDNO:46) MouseIL-10 >NM_010548.2Musmusculusinterleukin10(Il10),mRNA ACATTTAGAGACTTGCTCTTGCACTACCAAAGCCACAAGGCAGCCTTGCAGAAAAGA GAGCTCCATCATGCCTGGCTCAGCACTGCTATGCTGCCTGCTCTTACTGACTGGCAT GAGGATCAGCAGGGGCCAGTACAGCCGGGAAGACAATAACTGCACCCACTTCCCAGT CGGCCAGAGCCACATGCTCCTAGAGCTGCGGACTGCCTTCAGCCAGGTGAAGACTTT CTTTCAAACAAAGGACCAGCTGGACAACATACTGCTAACCGACTCCTTAATGCAGGA CTTTAAGGGTTACTTGGGTTGCCAAGCCTTATCGGAAATGATCCAGTTTTACCTGGT AGAAGTGATGCCCCAGGCAGAGAAGCATGGCCCAGAAATCAAGGAGCATTTGAATTC CCTGGGTGAGAAGCTGAAGACCCTCAGGATGCGGCTGAGGCGCTGTCATCGATTTCT CCCCTGTGAAAATAAGAGCAAGGCAGTGGAGCAGGTGAAGAGTGATTTTAATAAGCT CCAAGACCAAGGTGTCTACAAGGCCATGAATGAATTTGACATCTTCATCAACTGCAT AGAAGCATACATGATGATCAAAATGAAAAGCTAAAACACCTGCAGTGTGTATTGAGT CTGCTGGACTCCAGGACCTAGACAGAGCTCTCTAAATCTGATCCAGGGATCTTAGCT AACGGAAACAACTCCTTGGAAAACCTCGTTTGTACCTCTCTCCGAAATATTTATTAC CTCTGATACCTCAGTTCCCATTCTATTTATTCACTGAGCTTCTCTGTGAACTATTTA GAAAGAAGCCCAATATTATAATTTTACAGTATTTATTATTTTTAACCTGTGTTTAAG CTGTTTCCATTGGGGACACTTTATAGTATTTAAAGGGAGATTATATTATATGATGGG AGGGGTTCTTCCTTGGGAAGCAATTGAAGCTTCTATTCTAAGGCTGGCCACACTTGA GAGCTGCAGGGCCCTTTGCTATGGTGTCCTTTCAATTGCTCTCATCCCTGAGTTCAG AGCTCCTAAGAGAGTTGTGAAGAAACTCATGGGTCTTGGGAAGAGAAACCAGGGAGA TCCTTTGATGATCATTCCTGCAGCAGCTCAGAGGGTTCCCCTACTGTCATCCCCCAG CCGCTTCATCCCTGAAAACTGTGGCCAGTTTGTTATTTATAACCACCTAAAATTAGT TCTAATAGAACTCATTTTTAACTAGAAGTAATGCAATTCCTCTGGGAATGGTGTATT GTTTGTCTGCCTTTGTAGCAGACTCTAATTTTGAATAAATGGATCTTATTCG(SEQ IDNO:47) >NP_034678.1interleukin-10precursor[Musmusculus] MPGSALLCCLLLLTGMRISRGQYSREDNNCTHFPVGQSHMLLELRTAFSQVKTFFQT KDQLDNILLTDSLMQDFKGYLGCQALSEMIQFYLVEVMPQAEKHGPEIKEHLNSLGE KLKTLRMRLRRCHRFLPCENKSKAVEQVKSDFNKLQDQGVYKAMNEFDIFINCIEAY MMIKMKS(SEQIDNO:48) HumanTSG-6 >NM_007115.3HomosapiensTNFalphainducedprotein6 (TNFAIP6),mRNA AGTCACATTTCAGCCACTGCTCTGAGAATTTGTGAGCAGCCCCTAACAGGCTGTTAC TTCACTACAACTGACGATATGATCATCTTAATTTACTTATTTCTCTTGCTATGGGAA GACACTCAAGGATGGGGATTCAAGGATGGAATTTTTCATAACTCCATATGGCTTGAA CGAGCAGCCGGTGTGTACCACAGAGAAGCACGGTCTGGCAAATACAAGCTCACCTAC GCAGAAGCTAAGGCGGTGTGTGAATTTGAAGGCGGCCATCTCGCAACTTACAAGCAG CTAGAGGCAGCCAGAAAAATTGGATTTCATGTCTGTGCTGCTGGATGGATGGCTAAG GGCAGAGTTGGATACCCCATTGTGAAGCCAGGGCCCAACTGTGGATTTGGAAAAACT GGCATTATTGATTATGGAATCCGTCTCAATAGGAGTGAAAGATGGGATGCCTATTGC TACAACCCACACGCAAAGGAGTGTGGTGGCGTCTTTACAGATCCAAAGCAAATTTTT AAATCTCCAGGCTTCCCAAATGAGTACGAAGATAACCAAATCTGCTACTGGCACATT AGACTCAAGTATGGTCAGCGTATTCACCTGAGTTTTTTAGATTTTGACCTTGAAGAT GACCCAGGTTGCTTGGCTGATTATGTTGAAATATATGACAGTTACGATGATGTCCAT GGCTTTGTGGGAAGATACTGTGGAGATGAGCTTCCAGATGACATCATCAGTACAGGA AATGTCATGACCTTGAAGTTTCTAAGTGATGCTTCAGTGACAGCTGGAGGTTTCCAA ATCAAATATGTTGCAATGGATCCTGTATCCAAATCCAGTCAAGGAAAAAATACAAGT ACTACTTCTACTGGAAATAAAAACTTTTTAGCTGGAAGATTTAGCCACTTATAAAAA AAAAAAAAAGGATGATCAAAACACACAGTGTTTATGTTGGAATCTTTTGGAACTCCT TTGATCTCACTGTTATTATTAACATTTATTTATTATTTTTCTAAATGTGAAAGCAAT ACATAATTTAGGGAAAATTGGAAAATATAGGAAACTTTAAACGAGAAAATGAAACCT CTCATAATCCCACTGCATAGAAATAACAAGCGTTAACATTTTCATATTTTTTTCTTT CAGTCATTTTTCTATTTGTGGTATATGTATATATGTACCTATATGTATTTGCATTTG AAATTTTGGAATCCTGCTCTATGTACAGTTTTGTATTATACTTTTTAAATCTTGAAC TTTATAAACATTTTCTGAAATCATTGATTATTCTACAAAAACATGATTTTAAACAGC TGTAAAATATTCTATGATATGAATGTTTTATGCATTATTTAAGCCTGTCTCTATTGT TGGAATTTCAGGTCATTTTCATAAATATTGTTGCAATAAATATCCTTGAACACACAA AAAAAAAAAAAAAA(SEQIDNO:49) >NP_009046.2tumornecrosisfactor-induciblegene6 proteinprecursor[Homosapiens] MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAV CEFEGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYG IRLNRSERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQ RIHLSFLDFDLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLK FLSDASVTAGGFQIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHL(SEQID NO:50) MouseTSG-6 >NM_009398.2Musmusculustumornecrosisfactoralpha inducedprotein6(Tnfaip6),mRNA CCGCTGCTCTGAGAATTTCGTGTGGGCAGCCCCGACATTGTAACCGGCTCTGCAACC GAAGAGATGGTCGTCCTCCTTTGCTTATGCGTCTTGCTGTGGGAAGAGGCTCACGGA TGGGGATTCAAGAACGGGATCTTTCATAACTCCATATGGCTTGAACAAGCAGCGGGC GTATACCACAGAGAAGCTCGGGCTGGCAGATACAAGCTCACCTACGCCGAAGCCAAG GCCGTATGTGAATTTGAAGGTGGTCGTCTCGCAACCTACAAGCAGCTAGAGGCAGCC AGAAAAATTGGATTCCATGTCTGTGCTGCTGGATGGATGGCCAAGGGTAGAGTCGGA TACCCCATTGTGAAACCTGGGCCCAACTGTGGATTTGGGAAAACGGGTATCATCGAT TATGGAATCCGGCTCAACAGGAGTGAGCGATGGGATGCCTATTGCTACAACCCACAT GCAAAGGAGTGTGGTGGTGTCTTCACAGATCCGAAGCGAATTTTTAAATCCCCGGGC TTCCCAAATGAGTACGATGACAACCAGGTCTGCTACTGGCACATTCGGCTCAAGTAC GGTCAGCGAATTCACCTGAGCTTTTTGGACTTTGACCTTGAACATGATCCAGGCTGC TTGGCTGACTATGTAGAAATCTATGACAGTTATGATGACGTCCACGGCTTTGTAGGA AGATACTGTGGTGATGAACTTCCAGAAGACATCATTAGCACAGGAAATGTCATGACC TTGAAGTTTCTGAGTGATGCATCCGTCACGGCTGGAGGCTTCCAGATTAAATACGTC ACAGTGGATCCTGCATCTAAATCCAGTCAAGCCAAAAATACAAGTACTACTGGAAAT AAGAAGTTCTTACCTGGAAGGTTTAGCCATCTATAAAAAATTTTTTTTAAAAATGTT CAAAACATCCAGTACAATATTTATATTTGTTTTTGTTGTTGTTGTTGGTTTTTTTTT TTTTATTTTGTTTTGTTTTGTTTTTTTGAGACGGGGTTTCTCTGTATAGCCTTGGCT GTCCTGGAACTCACTTTGAAGACCAGGCTGGCCTCGAACTCAGAAATCCACCTGCCT CCGCCTACCAAGTGCTGGGATTAAAGGCGTCCACCACCACCGCCCGGCTTCAATATT TATATTTGTAGCTCTTGGACCTCGTTTGTTCTCTTTTGTATTTTTATTATTAACATG TATTTATTATTTTTCCAAATGTGAAAGCCATATGTAATTATGTGGAAAATTGACAAA TAAATACAGAGAACTTCAAATGAGTTTTTTTTTTAAATCTCATAATTGTACTACACA GAAATAACTAATGTTAAAGTTTTTAAATGTTTGTCTTTCATTCATTTTTCTACTTGT AGTATATGTACATATGTAACTCTATGATTTGCGTTTGAATTTTGGCATTCTGCCTTT TGTAACCTGATATTTTTAACCTTGACATTGTATAGCTCAAGCACTTCCCAAGATCTC TGAGTTTTCTACAAAATGGGACTTTGTAAATATGATTGTTCCCTGCTTTATTTAAGC TGAATTTATATTAGGATTTAAGGTTGTTTTCATAAATATTGCTGTAATAAATACTTT TGGAT(SEQIDNO:51) >NP_033424.1tumornecrosisfactor-induciblegene6 proteinprecursor[Musmusculus] MVVLLCLCVLLWEEAHGWGFKNGIFHNSIWLEQAAGVYHREARAGRYKLTYAEAKAV CEFEGGRLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYG IRLNRSERWDAYCYNPHAKECGGVFTDPKRIFKSPGFPNEYDDNQVCYWHIRLKYGQ RIHLSFLDFDLEHDPGCLADYVEIYDSYDDVHGFVGRYCGDELPEDIISTGNVMTLK FLSDASVTAGGFQIKYVTVDPASKSSQAKNTSTTGNKKFLPGRFSHL(SEQID NO:52) HumanB7-H3 >NM_001024736.2HomosapiensCD276molecule(CD276), (CD276) transcriptvariant1,mRNA ATTCGGGCCGGGCCTCGCTGCGGCGGCGACTGAGCCAGGCTGGGCCGCGTCCCTGAG TCCCAGAGTCGGCGCGGCGCGGCAGGGGCAGCCTTCCACCACGGGGAGCCCAGCTGT CAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCAT GTGGGTGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAG GTCCCTGAAGACCCAGTGGTGGCACTGGTGGGCACCGATGCCACCCTGTGCTGCTCC TTCTCCCCTGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCTGACA GATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCAGGACCAGGGCAGCGCCTAT GCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAGGGCAACGCATCCCTGAGG CTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGG GATTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGC ATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGC TCCAGCTACCAGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTG CCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGAT GTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACAGCTGCCTGGTG CGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTG GGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCA CAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACC GAAGGCCGGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTG CTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGC AGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAG GTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGG CCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAG GTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAG ATGGCCAACGAGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGT GCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCAC GGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTGGGTG ACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGC TGGAGAAAGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGAT GGGGAGGGAGAAGGCTCCAAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAA GAAGATGATGGACAAGAAATAGCCTGACCATGAGGACCAGGGAGCTGCTACCCCTCC CTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGTGAGCCCTGCCCCCAACA GATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACACAGACCA CTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTT TCTTATAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCC TGCTGCCTTATTTCACAGTACATACATTTCTTAGGGACACAGTACACTGACCACATC ACCACCCTCTTCTTCCAGTGCTGCGTGGACCATCTGGCTGCCTTTTTTCTCCAAAAG ATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTCACCAAAGACACGATGCATA GTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATGTTCAGCCC TGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACAT CTCCTGGAGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTT AATACTGGCCTTTTCCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCA CATGCACAGCTGTGCATGGAGACCTGCAGGTGCACGTGCTGGAACACGTGTGGTTCC CCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCCCTGCCCATCCTCCCCACGGAA GCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCCTGGGGGTCAG CTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAG TTGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTG CGTGGGAAGATAAAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAA CTAACTACACTGCACCCTGCGGTTTGCAGGGGGCTCCTGCCTGGCTCCCTGCTCCAC ACCTCCTCTGTGGCTCAAGGCTTCCTGGATACCTCACCCCCATCCCACCCATAATTC TTACCCAGAGCATGGGGTTGGGGCGGAAACCTGGAGAGAGGGACATAGCCCCTCGCC ACGGCTAGAGAATCTGGTGGTGTCCAAAATGTCTGTCCAGGTGTGGGCAGGTGGGCA GGCACCAAGGCCCTCTGGACCTTTCATAGCAGCAGAAAAGGCAGAGCCTGGGGCAGG GCAGGGCCAGGAATGCTTTGGGGACACCGAGGGGACTGCCCCCCACCCCCACCATGG TGCTATTCTGGGGCTGGGGCAGTCTTTTCCTGGCTTGCCTCTGGCCAGCTCCTGGCC TCTGGTAGAGTGAGACTTCAGACGTTCTGATGCCTTCCGGATGTCATCTCTCCCTGC CCCAGGAATGGAAGATGTGAGGACTTCTAATTTAAATGTGGGACTCGGAGGGATTTT GTAAACTGGGGGTATATTTTGGGGAAAATAAATGTCTTTGTAAAAA(SEQID NO:53) >NP_001019907.1CD276antigenisoformaprecursor[Homo sapiens] MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPG FSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRV ADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGY PEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQ QDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIW QLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFV SIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDG QGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTIT GQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQDGEGEGS KTALQPLKHSDSKEDDGQEIA(SEQIDNO:54) MouseB7-H3 >NM_133983.4MusmusculusCD276antigen(Cd276),mRNA (CD276) CGGCGCGGCGCGCCAAAGTGACCTGGTACAGCCTGGACCCCAAGCTCATCGGCTTTG TCTGGCTGGCCGCCTGGCCTCTTCCCACTTGGATTTGGATGATCCTGAGGCCTTTGG AGGAACTTCGAGACAAAGGCCCCTCTTCCTCTTCCACGGGCAGGAGCAGCCATTCGC CACGGAGAGCCCAGCTGTCAGCTGTCTCACAGGAAGATGCTTCGAGGATGGGGTGGC CCCAGTGTGGGTGTGTGTGTGCGCACAGCACTGGGGGTGCTGTGCCTCTGCCTCACA GGAGCTGTGGAAGTCCAGGTCTCTGAAGACCCCGTGGTGGCCCTGGTGGACACGGAT GCCACCCTACGCTGCTCCTTTTCCCCAGAGCCTGGCTTCAGTCTGGCACAGCTCAAC CTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGCTTCACGGAGGGCCGG GACCAAGGCAGTGCCTACTCCAACCGCACAGCGCTCTTCCCTGACCTGTTGGTGCAA GGCAATGCGTCCTTGAGGCTGCAGCGCGTCCGAGTAACCGACGAGGGCAGCTACACC TGCTTTGTGAGCATCCAGGACTTTGACAGCGCTGCTGTTAGCCTGCAGGTGGCCGCC CCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTACGTCCAGGGAAC ATGGTGACCATCACGTGCTCTAGCTACCAGGGCTATCCGGAGGCCGAGGTGTTCTGG AAGGATGGACAGGGAGTGCCCTTGACTGGCAATGTGACCACATCCCAGATGGCCAAC GAGCGGGGCTTGTTCGATGTTCACAGCGTGCTGAGGGTGGTGCTGGGTGCTAACGGC ACCTACAGCTGCCTGGTACGCAACCCGGTGTTGCAGCAAGATGCTCACGGCTCAGTC ACCATCACAGGGCAGCCCCTGACATTCCCCCCTGAGGCTCTGTGGGTAACCGTGGGG CTCTCTGTCTGTCTTGTGGTACTACTGGTGGCCCTGGCTTTCGTGTGCTGGAGAAAG ATCAAGCAGAGCTGCGAGGAGGAGAATGCAGGTGCCGAGGACCAGGATGGAGATGGA GAAGGATCCAAGACAGCTCTACGGCCTCTGAAACCCTCTGAAAACAAAGAAGATGAC GGACAAGAAATTGCTTGATTGGGAGCTGCTGCCCTTCCCAGGTGGGGGGCCCACCCT CTGGCAGTGTTGAGCTTCAATGCGAGCCCTTCCCCCAACGAATGGGTTTGTCCCACA GATCTACCCGTTCGTCAAAGGACGTGGTCCATAGACCACCCACAGCCTTACTTTTCC AATGGACTTAATTCCCATCATCCTGCAGCCTCATTTCTCCAGTGACACGATACACGA ACCATCCTGCGGCCTTATTTCCCACGGACACGACACAAAGATGTCCCTCCTCGGTGT TCCTCCAGAGTCGTCTGGTGGCCTTGTGATACGGCGTGAACCTTCTTCCTTCTGCCT TACGTCTAATGGACACACACGCACCACCCCCACACCCTTGCTCCTCCAAAGCCATGC AGACTGTGTAACTGCTATTATTCTCCAAGGGGCATCCTGTGCAGATGAAACCCTGCT TTATTTCCCTGAAGACAGCTGCACAGTGACCTCTTAGTTCTTGCTCCCATGGCCCTG ATGTATCCTAGTTACCAGCCCTCAACCTCAGTTCTGAGGGTGGGATCCCATCGCTCA GCAAGGCTTCATCCTGACCTCCCTGCCCTGATCTGATCTGGCCCTGGCTTTTGTTGT CTCGCTCCCTGACTAAGTGAGATGGGGCACTCTCCCGCCCCCGCCCCCCCCAGGTCA CAGATACCTACCTGCAGCTGTGCGTGCTGGATCACGCACATACTTGCCTTGCATGGT CTCCTGGCTGCCCTGGGCTGTGCCTGTTCTTCCATAGGAAGCAAGTTCTTGTCTCCC TGGTTCTCAGGGCCCCTCAGGGGCTCAGCCTTCAGCCCTGTGCTTCCCCATGTTGGG AATCTTTGTTACCTTTTTCTTCTTTGTAAATTAACATCTGATAACAACCACAGGGTC CAATGGGACTTTCACAGACCTGCCAGCTAGATAAATAATGACAACAGAAGTTTATTA ATATTTTAAGACTTAGGCCTTTTGCTGGGCAGCCTCCCAACTATTCTATCCTGACTA ATCCTGGCACTATGTCCCACCACATGGCCAGGTCTACCTCTCTGCTCCACTCTCCAT CCACCTCCATGTCTGCCAGCAAATCTCCCGTGATTCAGTTCTTCTCCCAGAGTCCCT ATCTCTGCCCAGAAGTACCATCTTCGACTTCCTGCCCAACTATTGGCCGTCAGCTCT TCATTAAAGCCGATCAGATGTAATTCTAGATTGCCTTAGGCAGGTGAGGAAGAAACA AGTATTTGTAAAATATGAGACCAGCAATGGGCCATAGAAATAACAGCACCAGATCCT GCCAGCATTTAGCCCTCTGTTGGTACAAAATTAACAATTGAATATACAGAGACCTAC TTCCAGAGTGTACCCCAACAACAGGCGTGAGCATGGTGCTGGGTACTAGGGTCCTGC TGGAAAATCAGAGACCTTACCTACAGCTGGGACATGACCTTGCTTCCGACTTACCCA CCACTTCTGGATACCTCACCCTCAGCCCACACTATCCCTGGCCTAGGGCCCAGGGTA GAGCCAGAAACATGGAGAAAGCATGGCCCCTTGCCGTACCTGGAGAACTGGGTATTT TCCAGAGTCTTTATAGATGTGGACTGGAAGGCAGGTGGCCACAGCCGTGCAGACCTG GGTCAGGTCAGAAACCTATGCCATGCTGGGACCTACTCAACAGCAGAAGCATGAAGA GGGCCTGAGGACAAGAAAGGCCTTCTTACCATGGTGCTATTCTGGAGCTGGGATATA TACCTGGCTTGTCTCTGACTGCCCTGGCTTCTGGCAGAACTTCTGATGTCCTCCTGA AGGCCTCTCTCCCACCCCAGTACCTGAGAACCTGAGGATAATTTAAACATGGGACTC TGGCCAGCACCTGGGAGAGACAGGTAGATCTCTGATTTTTGACTCAGCCTGGTCTAT CGAGTGAGTTCCAGGACATCTGGGGCTACACAGAGAAACCATCTTAAAGACTAAAAA TAATAAACATGAGACTGTAAACTGGGTGTATTTTGGGAGAAATAAATGTCTTTTTCT TTCAA(SEQIDNO:55) >NP_598744.1CD276antigenprecursor[Musmusculus] MLRGWGGPSVGVCVRTALGVLCLCLTGAVEVQVSEDPVVALVDTDATLRCSFSPEPG FSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYSNRTALFPDLLVQGNASLRLQRVRV TDEGSYTCFVSIQDFDSAAVSLQVAAPYSKPSMTLEPNKDLRPGNMVTITCSSYQGY PEAEVFWKDGQGVPLTGNVTTSQMANERGLFDVHSVLRVVLGANGTYSCLVRNPVLQ QDAHGSVTITGQPLTFPPEALWVTVGLSVCLVVLLVALAFVCWRKIKQSCEEENAGA EDQDGDGEGSKTALRPLKPSENKEDDGQEIA(SEQIDNO:56) HumanB7-H4 >NM_024626.4HomosapiensV-setdomaincontainingTcell (VTCN1) activationinhibitor1(VTCN1),transcriptvariant1, mRNA GTGAGTCACCAAGGAAGGCAGCGGCAGCTCCACTCAGCCAGTACCCAGATACGCTGG GAACCTTCCCCAGCCATGGCTTCCCTGGGGCAGATCCTCTTCTGGAGCATAATTAGC ATCATCATTATTCTGGCTGGAGCAATTGCACTCATCATTGGCTTTGGTATTTCAGGG AGACACTCCATCACAGTCACTACTGTCGCCTCAGCTGGGAACATTGGGGAGGATGGA ATCCTGAGCTGCACTTTTGAACCTGACATCAAACTTTCTGATATCGTGATACAATGG CTGAAGGAAGGTGTTTTAGGCTTGGTCCATGAGTTCAAAGAAGGCAAAGATGAGCTG TCGGAGCAGGATGAAATGTTCAGAGGCCGGACAGCAGTGTTTGCTGATCAAGTGATA GTTGGCAATGCCTCTTTGCGGCTGAAAAACGTGCAACTCACAGATGCTGGCACCTAC AAATGTTATATCATCACTTCTAAAGGCAAGGGGAATGCTAACCTTGAGTATAAAACT GGAGCCTTCAGCATGCCGGAAGTGAATGTGGACTATAATGCCAGCTCAGAGACCTTG CGGTGTGAGGCTCCCCGATGGTTCCCCCAGCCCACAGTGGTCTGGGCATCCCAAGTT GACCAGGGAGCCAACTTCTCGGAAGTCTCCAATACCAGCTTTGAGCTGAACTCTGAG AATGTGACCATGAAGGTTGTGTCTGTGCTCTACAATGTTACGATCAACAACACATAC TCCTGTATGATTGAAAATGACATTGCCAAAGCAACAGGGGATATCAAAGTGACAGAA TCGGAGATCAAAAGGCGGAGTCACCTACAGCTGCTAAACTCAAAGGCTTCTCTGTGT GTCTCTTCTTTCTTTGCCATCAGCTGGGCACTTCTGCCTCTCAGCCCTTACCTGATG CTAAAATAATGTGCCTCGGCCACAAAAAAGCATGCAAAGTCATTGTTACAACAGGGA TCTACAGAACTATTTCACCACCAGATATGACCTAGTTTTATATTTCTGGGAGGAAAT GAATTCATATCTAGAAGTCTGGAGTGAGCAAACAAGAGCAAGAAACAAAAAGAAGCC AAAAGCAGAAGGCTCCAATATGAACAAGATAAATCTATCTTCAAAGACATATTAGAA GTTGGGAAAATAATTCATGTGAACTAGACAAGTGTGTTAAGAGTGATAAGTAAAATG CACGTGGAGACAAGTGCATCCCCAGATCTCAGGGACCTCCCCCTGCCTGTCACCTGG GGAGTGAGAGGACAGGATAGTGCATGTTCTTTGTCTCTGAATTTTTAGTTATATGTG CTGTAATGTTGCTCTGAGGAAGCCCCTGGAAAGTCTATCCCAACATATCCACATCTT ATATTCCACAAATTAAGCTGTAGTATGTACCCTAAGACGCTGCTAATTGACTGCCAC TTCGCAACTCAGGGGCGGCTGCATTTTAGTAATGGGTCAAATGATTCACTTTTTATG ATGCTTCCAAAGGTGCCTTGGCTTCTCTTCCCAACTGACAAATGCCAAAGTTGAGAA AAATGATCATAATTTTAGCATAAACAGAGCAGTCGGCGACACCGATTTTATAAATAA ACTGAGCACCTTCTTTTTAAACAAACAAATGCGGGTTTATTTCTCAGATGATGTTCA TCCGTGAATGGTCCAGGGAAGGACCTTTCACCTTGTCTATATGGCATTATGTCATCA CAAGCTCTGAGGCTTCTCCTTTCCATCCTGCGTGGACAGCTAAGACCTCAGTTTTCA ATAGCATCTAGAGCAGTGGGACTCAGCTGGGGTGATTTCGCCCCCCATCTCCGGGGG AATGTCTGAAGACAATTTTGGTTACCTCAATGAGGGAGTGGAGGAGGATACAGTGCT ACTACCAACTAGTGGATAGAGGCCAGGGATGCTGCTCAACCTCCTACCATGTACAGG ACGTCTCCCCATTACAACTACCCAATCCGAAGTGTCAACTGTGTCAGGGCTAAGAAA CCCTGGTTTTGAGTAGAAAAGGGCCTGGAAAGAGGGGAGCCAACAAATCTGTCTGCT TCCTCACATTAGTCATTGGCAAATAAGCATTCTGTCTCTTTGGCTGCTGCCTCAGCA CAGAGAGCCAGAACTCTATCGGGCACCAGGATAACATCTCTCAGTGAACAGAGTTGA CAAGGCCTATGGGAAATGCCTGATGGGATTATCTTCAGCTTGTTGAGCTTCTAAGTT TCTTTCCCTTCATTCTACCCTGCAAGCCAAGTTCTGTAAGAGAAATGCCTGAGTTCT AGCTCAGGTTTTCTTACTCTGAATTTAGATCTCCAGACCCTGCCTGGCCACAATTCA AATTAAGGCAACAAACATATACCTTCCATGAAGCACACACAGACTTTTGAAAGCAAG GACAATGACTGCTTGAATTGAGGCCTTGAGGAATGAAGCTTTGAAGGAAAAGAATAC TTTGTTTCCAGCCCCCTTCCCACACTCTTCATGTGTTAACCACTGCCTTCCTGGACC TTGGAGCCACGGTGACTGTATTACATGTTGTTATAGAAAACTGATTTTAGAGTTCTG ATCGTTCAAGAGAATGATTAAATATACATTTCCTACACCA(SEQIDNO:57) >NP_078902.2V-setdomain-containingT-cellactivation inhibitor1isoform1precursor[Homosapiens] MASLGQILFWSIISIIIILAGAIALIIGFGISGRHSITVTTVASAGNIGEDGILSCT FEPDIKLSDIVIQWLKEGVLGLVHEFKEGKDELSEQDEMFRGRTAVFADQVIVGNAS LRLKNVQLTDAGTYKCYIITSKGKGNANLEYKTGAFSMPEVNVDYNASSETLRCEAP RWFPQPTVVWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIE NDIAKATGDIKVTESEIKRRSHLQLLNSKASLCVSSFFAISWALLPLSPYLMLK (SEQIDNO:58) MouseB7-H4 >NM_178594.3MusmusculusV-setdomaincontainingTcell (VTCN1) activationinhibitor1(Vtcn1),mRNA GTGAGTCACAACACCCAGGAGGGCAGCAGCAGGCAGGCAGCTCCACTCACCAAAATC TGGCCCCACACACAGCAGGACTGTGGGAAGGAACTCCCTCTCCATGGCTTCCTTGGG GCAGATCATCTTTTGGAGTATTATTAACATCATCATCATCCTGGCTGGGGCCATCGC ACTCATCATTGGCTTTGGCATTTCAGGCAAGCACTTCATCACGGTCACGACCTTCAC CTCAGCTGGAAACATTGGAGAGGACGGGACCCTGAGCTGCACTTTTGAACCTGACAT CAAACTCAACGGCATCGTCATCCAGTGGCTGAAAGAAGGCATCAAAGGTTTGGTCCA CGAGTTCAAAGAAGGCAAAGACGACCTCTCACAGCAGCATGAGATGTTCAGAGGCCG CACAGCAGTGTTTGCTGATCAGGTGGTAGTTGGCAATGCTTCCCTGAGACTGAAAAA CGTGCAGCTCACGGATGCTGGCACCTACACATGTTACATCCGCACCTCAAAAGGCAA AGGGAATGCAAACCTTGAGTATAAGACCGGAGCCTTCAGTATGCCAGAGATAAATGT GGACTATAATGCCAGTTCAGAGAGTTTACGCTGCGAGGCTCCTCGGTGGTTCCCCCA GCCCACAGTGGCCTGGGCATCTCAAGTCGACCAAGGAGCCAATTTCTCAGAAGTCTC CAACACCAGCTTTGAGTTGAACTCTGAGAATGTGACCATGAAGGTCGTATCTGTGCT CTACAATGTCACAATCAACAACACATACTCCTGTATGATTGAAAACGACATTGCCAA AGCCACCGGGGACATCAAAGTGACAGATTCAGAGGTCAAAAGGCGAAGTCAGCTGCA GTTGCTGAACTCTGGGCCTTCCCCGTGTGTTTTTTCTTCTGCCTTTGTGGCTGGCTG GGCACTCCTATCTCTCTCCTGTTGCCTGATGCTAAGATGAGGGGCCCTGGCTACACA AAAGCATGCAACGTTGCTGGTCCAACAGAATCCCGGAGAACTACAGAAATATTTTCC TCAAGACATGACCTAGTTTTATATTTCTAGAAGAAGATGAAATCATGTCTAGAAGTC TGGAGAGAGCAGACAGGAACAAGATGTGGAAGGAAAACAAAAGTAACCCACAGACAC CCCCGATCGGAACAAGATGGACCTAGAAAATAATTCAACCAAACTAGAGTATACTAA GTGTGCTGTTACAATGTGTGTAGGGTAGGTGTCCTCCCACATCTCAGGGGCCTCCCC TGGTCCACCAGCTCCTGAGTTAGGATGGGCTGTTATGATGTCACTCTGAAGGTTCCT GGATGGTTCCTACTGCCATATACTCATTTTATATTCAGCACATTAAACCATAGTGAA TGCTATGAAAAGCTGCTAATCAGCTGCCACTCCGAGATTCGGAGGTGGCAACGTCTG AGTGACAGGTCCAGTGATTCGCTTCTCCTTAGGATGCTTTTACAAGCTCTTTGGCGT CTCCTCCCACCTGGCAAATGCCAAATGCATAGGGGAGGGTGATCATCATTCTAGGGC AAACAAAATAGTTGAGGGATGCTGATTTCCCAAATCATCCGAATCACTTCTCCCTTG AGCAAACAAGCGCCCTGTTATTTCTCAAATGCTGCTTTGTGAATCAGTCCAGGGCAA GGCGCTCTCCTCATCCCGCTATGTGGCCTTAAGTCATCGTAAGGTTTGAAGTTTCTA CTTTCGATCCTGCATGGAGAGCTATAATCTCAGCTCCCCCGCCCCCCCCACACACAC CTCTGCACACACACCCCCCCCCAACACTGGGAGTAAACCAGGATGATGTCCGTCTTC TCATTCCCCATGTGACCGTTGGCAGTGTAGAGAGACTGATTGTCACAGCTAAAGGAA GAGGGACAACAGGGTCACTGGTGTCTACAGAGATTATATTCTACGTGTCTCACTGAA TTTACACAACTCCAAGTGCCAACCACATCAAGGTCAGGAAATCCTGAACTGGAATAA GAAAGACCCAGAAGATGAATGTGAACAGATCCATTTGCTTCCCGACAGTGGGCACAG ACTTCAGTCTCTGGCTACTGTTCCAAGACCCAGGGCTCTGCAATTGTGTGACATCCT TCAGTGAACCCACATGGGAAATTCTCCATGGAATTATCTTCAGCCCACTGTACTTCT GAATCCCTCTTCCTTCCTTCTGTGCCACACAGCAAGTCTGGCTTAAATGCTGCCTGA TCTCCATTTCAAGTTTTCTGCCTCTGGATTTTTAGATCTCAAGACCATGGACGAAAC ATCAGTTACAGCAACAAAAGTGAATTTTCCGTGCAGAGACTTCTAGGGGTTCTGTTT GTTTTCAGGGTGCTAGAGATCACACTCAGATGCTCATATATGTTAGGTAAATGTTCT CCCACTGAGTTACAGCCCAGCTCACACAGAGACTTCTAAAAGAAAATACGGCCATGC TCTTTGAAATGGAGCATTGAGGGATGAAGTTTGGATGGCGAAGAAAACTTCTCACCA GCTCTCTCCCCACATTCGTGCCAAGCACTGCCTCCCTAGACTTCGGGTCACCATATC TGTACTACGTTTTGATACAGAAGGCTCGAGACCATTCAAGAGAATTATTTAGTACAC (SEQIDNO:59) >NP_848709.2V-setdomaincontainingT-cellactivation inhibitor1precursor[Musmusculus] MASLGQIIFWSIINIIIILAGAIALIIGFGISGKHFITVTTFTSAGNIGEDGTLSCT FEPDIKLNGIVIQWLKEGIKGLVHEFKEGKDDLSQQHEMFRGRTAVFADQVVVGNAS LRLKNVQLTDAGTYTCYIRTSKGKGNANLEYKTGAFSMPEINVDYNASSESLRCEAP RWFPQPTVAWASQVDQGANFSEVSNTSFELNSENVTMKVVSVLYNVTINNTYSCMIE NDIAKATGDIKVTDSEVKRRSQLQLLNSGPSPCVESSAFVAGWALLSLSCCLMLR (SEQIDNO:60) HumanB7-H5 >NM_022153.2HomosapiensV-setimmunoregulatoryreceptor (VISTA) (VSIR),mRNA AGTCGCGGGAGGCTTCCCCGCGCCGGCCGCGTCCCGCCCGCTCCCCGGCACCAGAAG TTCCTCTGCGCGTCCGACGGCGACATGGGCGTCCCCACGGCCCTGGAGGCCGGCAGC TGGCGCTGGGGATCCCTGCTCTTCGCTCTCTTCCTGGCTGCGTCCCTAGGTCCGGTG GCAGCCTTCAAGGTCGCCACGCCGTATTCCCTGTATGTCTGTCCCGAGGGGCAGAAC GTCACCCTCACCTGCAGGCTCTTGGGCCCTGTGGACAAAGGGCACGATGTGACCTTC TACAAGACGTGGTACCGCAGCTCGAGGGGCGAGGTGCAGACCTGCTCAGAGCGCCGG CCCATCCGCAACCTCACGTTCCAGGACCTTCACCTGCACCATGGAGGCCACCAGGCT GCCAACACCAGCCACGACCTGGCTCAGCGCCACGGGCTGGAGTCGGCCTCCGACCAC CATGGCAACTTCTCCATCACCATGCGCAACCTGACCCTGCTGGATAGCGGCCTCTAC TGCTGCCTGGTGGTGGAGATCAGGCACCACCACTCGGAGCACAGGGTCCATGGTGCC ATGGAGCTGCAGGTGCAGACAGGCAAAGATGCACCATCCAACTGTGTGGTGTACCCA TCCTCCTCCCAGGATAGTGAAAACATCACGGCTGCAGCCCTGGCTACGGGTGCCTGC ATCGTAGGAATCCTCTGCCTCCCCCTCATCCTGCTCCTGGTCTACAAGCAAAGGCAG GCAGCCTCCAACCGCCGTGCCCAGGAGCTGGTGCGGATGGACAGCAACATTCAAGGG ATTGAAAACCCCGGCTTTGAAGCCTCACCACCTGCCCAGGGGATACCCGAGGCCAAA GTCAGGCACCCCCTGTCCTATGTGGCCCAGCGGCAGCCTTCTGAGTCTGGGCGGCAT CTGCTTTCGGAGCCCAGCACCCCCCTGTCTCCTCCAGGCCCCGGAGACGTCTTCTTC CCATCCCTGGACCCTGTCCCTGACTCTCCAAACTTTGAGGTCATCTAGCCCAGCTGG GGGACAGTGGGCTGTTGTGGCTGGGTCTGGGGCAGGTGCATTTGAGCCAGGGCTGGC TCTGTGAGTGGCCTCCTTGGCCTCGGCCCTGGTTCCCTCCCTCCTGCTCTGGGCTCA GATACTGTGACATCCCAGAAGCCCAGCCCCTCAACCCCTCTGGATGCTACATGGGGA TGCTGGACGGCTCAGCCCCTGTTCCAAGGATTTTGGGGTGCTGAGATTCTCCCCTAG AGACCTGAAATTCACCAGCTACAGATGCCAAATGACTTACATCTTAAGAAGTCTCAG AACGTCCAGCCCTTCAGCAGCTCTCGTTCTGAGACATGAGCCTTGGGATGTGGCAGC ATCAGTGGGACAAGATGGACACTGGGCCACCCTCCCAGGCACCAGACACAGGGCACG GTGGAGAGACTTCTCCCCCGTGGCCGCCTTGGCTCCCCCGTTTTGCCCGAGGCTGCT CTTCTGTCAGACTTCCTCTTTGTACCACAGTGGCTCTGGGGCCAGGCCTGCCTGCCC ACTGGCCATCGCCACCTTCCCCAGCTGCCTCCTACCAGCAGTTTCTCTGAAGATCTG TCAACAGGTTAAGTCAATCTGGGGCTTCCACTGCCTGCATTCCAGTCCCCAGAGCTT GGTGGTCCCGAAACGGGAAGTACATATTGGGGCATGGTGGCCTCCGTGAGCAAATGG TGTCTTGGGCAATCTGAGGCCAGGACAGATGTTGCCCCACCCACTGGAGATGGTGCT GAGGGAGGTGGGTGGGGCCTTCTGGGAAGGTGAGTGGAGAGGGGCACCTGCCCCCCG CCCTCCCCATCCCCTACTCCCACTGCTCAGCGCGGGCCATTGCAAGGGTGCCACACA ATGTCTTGTCCACCCTGGGACACTTCTGAGTATGAAGCGGGATGCTATTAAAAACTA CATGGGGAAACAGGTGCAAACCCTGGAGATGGATTGTAAGAGCCAGTTTAAATCTGC ACTCTGCTGCTCCTCCCCCACCCCCACCTTCCACTCCATACAATCTGGGCCTGGTGG AGTCTTCGCTTCAGAGCCATTCGGCCAGGTGCGGGTGATGTTCCCATCTCCTGCTTG TGGGCATGCCCTGGCTTTGTTTTTATACACATAGGCAAGGTGAGTCCTCTGTGGAAT TGTGATTGAAGGATTTTAAAGCAGGGGAGGAGAGTAGGGGGCATCTCTGTACACTCT GGGGGTAAAACAGGGAAGGCAGTGCCTGAGCATGGGGACAGGTGAGGTGGGGCTGGG CAGACCCCCTGTAGCGTTTAGCAGGATGGGGGCCCCAGGTACTGTGGAGAGCATAGT CCAGCCTGGGCATTTGTCTCCTAGCAGCCTACACTGGCTCTGCTGAGCTGGGCCTGG GTGCTGAAAGCCAGGATTTGGGGCTAGGCGGGAAGATGTTCGCCCAATTGCTTGGGG GGTTGGGGGGATGGAAAAGGGGAGCACCTCTAGGCTGCCTGGCAGCAGTGAGCCCTG GGCCTGTGGCTACAGCCAGGGAACCCCACCTGGACACATGGCCCTGCTTCTAAGCCC CCCAGTTAGGCCCAAAGGAATGGTCCACTGAGGGCCTCCTGCTCTGCCTGGGCTGGG CCAGGGGCTTTGAGGAGAGGGTAAACATAGGCCCGGAGATGGGGCTGACACCTCGAG TGGCCAGAATATGCCCAAACCCCGGCTTCTCCCTTGTCCCTAGGCAGAGGGGGGTCC CTTCTTTTGTTCCCTCTGGTCACCACAATGCTTGATGCCAGCTGCCATAGGAAGAGG GTGCTGGCTGGCCATGGTGGCACACACCTGTCCTCCCAGCACTTTGCAGGGCTGAGG TGGAAGGACCGCTTAAGCCCAGGTGTTCAAGGCTGCTGTGAGCTGTGTTCGAGCCAC TACACTCCAGCCTGGGGACGGAGCAAAACTTTGCCTCAAAACAAATTTTAAAAAGAA AGAAAGAAGGAAAGAGGGTATGTTTTTCACAATTCATGGGGGCCTGCATGGCAGGAG TGGGGACAGGACACCTGCTGTTCCTGGAGTCGAAGGACAAGCCCACAGCCCAGATTC CGGTTCTCCCAACTCAGGAAGAGCATGCCCTGCCCTCTGGGGAGGCTGGCCTGGCCC CAGCCCTCAGCTGCTGACCTTGAGGCAGAGACAACTTCTAAGAATTTGGCTGCCAGA CCCCAGGCCTGGCTGCTGCTGTGTGGAGAGGGAGGCGGCCCGCAGCAGAACAGCCAC CGCACTTCCTCCTCAGCTTCCTCTGGTGCGGCCCTGCCCTCTCTTCTCTGGACCCTT TTACAACTGAACGCATCTGGGCTTCGTGGTTTCCTGTTTTCAGCGAAATTTACTCTG AGCTCCCAGTTCCATCTTCATCCATGGCCACAGGCCCTGCCTACAACGCACTAGGGA CGTCCCTCCCTGCTGCTGCTGGGGAGGGGCAGGCTGCTGGAGCCGCCCTCTGAGTTG CCCGGGATGGTAGTGCCTCTGATGCCAGCCCTGGTGGCTGTGGGCTGGGGTGCATGG GAGAGCTGGGTGCGAGAACATGGCGCCTCCAGGGGGCGGGAGGAGCACTAGGGGCTG GGGCAGGAGGCTCCTGGAGCGCTGGATTCGTGGCACAGTCTGAGGCCCTGAGAGGGA AATCCATGCTTTTAAGAACTAATTCATTGTTAGGAGATCAATCAGGAATTAGGGGCC ATCTTACCTATCTCCTGACATTCACAGTTTAATAGAGACTTCCTGCCTTTATTCCCT CCCAGGGAGAGGCTGAAGGAATGGAATTGAAAGCACCATTTGGAGGGTTTTGCTGAC ACAGCGGGGACTGCTCAGCACTCCCTAAAAACACACCATGGAGGCCACTGGTGACTG CTGGTGGGCAGGCTGGCCCTGCCTGGGGGAGTCCGTGGCGATGGGCGCTGGGGTGGA GGTGCAGGAGCCCCAGGACCTGCTTTTCAAAAGACTTCTGCCTGACCAGAGCTCCCA CTACATGCAGTGGCCCAGGGCAGAGGGGCTGATACATGGCCTTTTTCAGGGGGTGCT CCTCGCGGGGTGGACTTGGGAGTGTGCAGTGGGACAGGGGGCTGCAGGGGTCCTGCC ACCACCGAGCACCAACTTGGCCCCTGGGGTCCTGCCTCATGAATGAGGCCTTCCCCA GGGCTGGCCTGACTGTGCTGGGGGCTGGGTTAACGTTTTCTCAGGGAACCACAATGC ACGAAAGAGGAACTGGGGTTGCTAACCAGGATGCTGGGAACAAAGGCCTCTTGAAGC CCAGCCACAGCCCAGCTGAGCATGAGGCCCAGCCCATAGACGGCACAGGCCACCTGG CCCATTCCCTGGGCATTCCCTGCTTTGCATTGCTGCTTCTCTTCACCCCATGGAGGC TATGTCACCCTAACTATCCTGGAATGTGTTGAGAGGGATTCTGAATGATCAATATAG CTTGGTGAGACAGTGCCGAGATAGATAGCCATGTCTGCCTTGGGCACGGGAGAGGGA AGTGGCAGCATGCATGCTGTTTCTTGGCCTTTTCTGTTAGAATACTTGGTGCTTTCC AACACACTTTCACATGTGTTGTAACTTGTTTGATCCACCCCCTTCCCTGAAAATCCT GGGAGGTTTTATTGCTGCCATTTAACACAGAGGGCAATAGAGGTTCTGAAAGGTCTG TGTCTTGTCAAAACAAGTAAACGGTGGAACTACGACTAAA(SEQIDNO:61) >NP_071436.1V-typeimmunoglobulindomain-containing suppressorofT-cellactivationprecursor[Homosapiens] MGVPTALEAGSWRWGSLLFALFLAASLGPVAAFKVATPYSLYVCPEGQNVTLTCRLL GPVDKGHDVTFYKTWYRSSRGEVQTCSERRPIRNLTFQDLHLHHGGHQAANTSHDLA QRHGLESASDHHGNFSITMRNLTLLDSGLYCCLVVEIRHHHSEHRVHGAMELQVQTG KDAPSNCVVYPSSSQDSENITAAALATGACIVGILCLPLILLLVYKQRQAASNRRAQ ELVRMDSNIQGIENPGFEASPPAQGIPEAKVRHPLSYVAQRQPSESGRHLLSEPSTP LSPPGPGDVFFPSLDPVPDSPNFEVI(SEQIDNO:62) MouseB7-H5 >NM_028732.4MusmusculusV-setimmunoregulatoryreceptor (VISTA) (Vsir),transcriptvariant1,mRNA GGGGGCGCTGCTGGGCGGGGAGCTTGCTCGGCCGCCTGCCTCGCCTTGGGCTCAGCA TTCACTCTAGCGAGCGAGCGGCGTGTACAGCCGGCTCCCTGGGCTCCTGGAGTCCCG CTTGCTCCAAGCGCACTCCAGCAGTCTCTTTCTGCTCTTGCCCGGCTCGACGGCGAC ATGGGTGTCCCCGCGGTCCCAGAGGCCAGCAGCCCGCGCTGGGGAACCCTGCTCCTT GCTATTTTCCTGGCTGCATCCAGAGGTCTGGTAGCAGCCTTCAAGGTCACCACTCCA TATTCTCTCTATGTGTGTCCCGAGGGACAGAATGCCACCCTCACCTGCAGGATTCTG GGCCCCGTGTCCAAAGGGCACGATGTGACCATCTACAAGACGTGGTACCTCAGCTCA CGAGGCGAGGTCCAGATGTGCAAAGAACACCGGCCCATACGCAACTTCACATTGCAG CACCTTCAGCACCACGGAAGCCACCTGAAAGCCAACGCCAGCCATGACCAGCCCCAG AAGCATGGGCTAGAGCTAGCTTCTGACCACCACGGTAACTTCTCTATCACCCTGCGC AATGTGACCCCAAGGGACAGCGGCCTCTACTGCTGTCTAGTGATAGAATTAAAAAAC CACCACCCAGAACAACGGTTCTACGGGTCCATGGAGCTACAGGTACAGGCAGGCAAA GGCTCGGGGTCCACATGCATGGCGTCTAATGAGCAGGACAGTGACAGCATCACGGCT GCGGCCCTGGCCACCGGCGCCTGCATCGTGGGAATCCTCTGCCTCCCCCTTATCCTG CTGCTGGTCTATAAGCAGAGACAGGTGGCCTCTCACCGCCGTGCCCAGGAGTTGGTG AGGATGGACAGCAGCAACACCCAAGGAATCGAAAACCCAGGCTTCGAGACCACTCCA CCCTTCCAGGGGATGCCTGAGGCCAAGACCAGGCCGCCACTGTCCTATGTGGCCCAG CGGCAACCTTCGGAGTCAGGACGGTACCTGCTCTCTGACCCCAGCACACCTCTGTCG CCTCCAGGCCCTGGGGACGTCTTTTTCCCATCCCTAGATCCAGTCCCTGACTCCCCT AACTCTGAAGCCATCTAAACCAGCTGGGGAACCATGAACCATGGTACCTGGGTCAGG GATATGTGCACTTGATCTATGGCTGGCCCTTGGACAGTCTTTTAGGCACTGACTCCA GCTTCCTTGCTCCTGCTCTGAGCCTAGACTCTGCTTTTACAAGATGCACAGACCCTC CCCTATCTCTTTCAGACGCTACTTGGGGGGCAGGGAGAAGATGTTGGATTGCTCATT GCTGTTCTCAAGATCTTGGGATGCTGAGTTCTCCCTAGAGACTTGACTTCGACAGCC ACAGATGTCAGATGACCTGCATCCTATGAACGTCCGGCTTGGCAAGAGCCTTTCTTC ATGGAAACCAGTAGCCCGGAGGGGATGAGGTAGGCACCTTGCCACCCTCCCGGGAGA GAGACACAAGATGTGAGAGACTCCTGCTCACTGTGGGGGTGTGGCTGGCCTGCTTGT TTGCCTGAGGATGCTCCTCTGTTGGACTGACTCTATCCCCCTGGATTCTGGAGCTTG GCTGGCCTATGTCCCACCAGAGGAGCATCTCAGCAGCCTTCCACCAGCAACCTGAGG GCCTGCCAGCTTCGTGGCTCTGGGCTCTCATTACCTGTATGGCCGTCCACAGAGCTC AGTGGCCAGAGGCTTTGAAACAGGAAGTACATGTCAGGTTCAGGAACCACTGTGAGC TCATTAGTGTCTTGAGCAATGTGAGGCCTGGACCAGTGGACACGGAGGGAGGGTGGC GAGAGGATGATGGGGATGATGAGGGGAACACGCTCCCTTCCTGTCCTTGTCATCCAC CACTACCACTATTCAGTGTGGAGCAGTGGCAAAGGTGACCGACCTCCACAATGTCCT AGTGATGCTGGACCATTTCTAAGTGTGAAAGAGATGCTATTAAAAACAGTATGTGGC AATGGCTGCCAACAGCTGAGTGGACTGGAGGCACTGGCTTTAAGGCCCTGGAGGTGC AGGGCCCGGTATGGGGATAGGGATGGGAGTTTCAGTGAGGGCCTAGGGATCACTCCG CTTCTGACCACTCTTCTTCTGAGCCTCACCTCAGGGTGACCTTCAGGCACACAGAAG AGCTTGCCCCTGGTCCGATACTACTCTTGGCTCTCATCTCCAGGGTTTGGCATGACC TGGGCACACAGGGGGAGTCTTCAGAAAGGATTTTAAAGCATGAAAAGAAAGGGTAGT TCTTGTGAGGTAGGGATGGGCAGCTGATGTTTGAGAGTGAGGAGGGATACGGCTGGG CAGATCACTCTCCAGTCTCTAGAGGGAAAGTAGCTCTAAGTCTGGGAGAGCAGCAGC CCAGTGGTACCATATGTCTTCTTGCAGCTTCCACTGGCTGGGCTGAACTGGGCATGG GTAGGAAAGCTCCTGTTCTGGGCCTGCAGCCAGGGAGAACCCCATTCATTCCCTGAG GACAGATGGGTGGGGAGAGAAGAGAGAGTTTCAGGCCGGGAAGCAGCAATAAGCTAT CTGCTGGGGACCCAGACAAGTTGTCTGATGAGGTCCAAGATGTGGGATGCCAGTTAT ACCTGGGGCTTGGGGATCCTTAGAGGCTTTGTATCATCATCATAGGAGTGTCGGGGT GGCCAGGGCATCAAAGCCATGACCCCTGTTTTATCCTCAGGGTCCACTCTTCTGCAC CATCCATTGCTCTAGATCTATGCAGTTACTATAGACAGAATGTGTTGTTCTGTTTGG CTTTGGGGATAATGGCCTGGCGAACTGCCAGCTGTTCAGTGGCAGGGCTGTGAGGCC AGTCAAAGACTAGAACCCACAGACCAGCTGAACGATGAGTATAGCCTGTCCCCTGGG GGAGCCTGACCTGTCTCCAGCCCTAAGCTTCAGACCTCACCACTCAGATGACTTCTA AGAATTTGCCTGTGGGGACCCCTGCATGGCTGCAGCTCCGTGGAAAGGAGAGGAGGC CCCCAGCAGAAGAACCACTCGCTTCCTGCCCAGCTTCCTCCTGTAGGGCTCTAAGTC TCTTCTTCTTGGGACCCTGCAAGCAAAGGCATGTCAGCTTGGTGGTTTCCTGTTTTG GGTGAAGTTTTGTGTGGTCCGGGTTCTGTCTACATCCATGAACTTGGGTGCTACCAC CTTGCTGCTGCTGTAGAGACAGCTGCAGGATCTTAGGGTGGAAAATGGAGGTGCCCT GAGGTGCTAGCCCTTGGGGCAAAAGATGGGGTGGCAATGAGACACAGTGGGGAACTG AGTTCCCCAAGAGGAGGGAGGAGCCCTGTAGCCTCAAGGGCCATATTGGGTTCCTGG TACCAGCAAAAGCCTAGAGAGCGAAGTCTGTATTTTGAGGAGGTAATTGATCCTTAC GGAATCCATCAGAAATTTGGAGCGGGTGCTTTATCTATCTCTGGAGGGTCTCTACCT ATCTCCGATGAAGCTCTCCCTGGGCCTGGGATGGGAGAAACCAGGAGGAAAGGTGTC TGATAAAGCAGGGGCTTCTTGACAAGCCAAAGGGCCACTGGTAGCTGTTGTGGACCG AGCTGACCCTGCTGAAGTATTGTAGTGTGCCTTGGACCAACTTCTCAAAAGAGCAAC CCCGGGGCTACCCTACTTCTGCCAGGAAGAGGCGGAGAAGGGGCTGAGAGGCCTGGA AGGGGCTAGCTCCTTCTTTGAGAACTGCTCCCCGGAGGACTTGGAGGAGGCGGCTAG GCTACGGGCTGCTGAGGGCCCTTTGTCTTTCCTAACCTGGGCACTGTTAGGATGCTC CCTCCTGGAAAAGGCTTTCCTGGGTGTGAGCTAGAGCAGTGTCCATGCCAGCGCTGA ACCTGCCATGGTGGGAGCTGAACTAAAAATTTCTCAGGGAACTAAAATAGGCAAAAG AGGAACTGGGGGAGGAGGGTGCCAGGCAGGATGGGGGGAAGGGAGGGCAGTGCAAAA GTCTCTTGAAACACAGACAGCCCAGCTGAGTGCCAGTCCCAGATCACAGAGAATACG GCTCATCTGGCTCATGTTCTGCATGCTTGCTGCTTTACCCTGGCACTTTCCTTCTCC ACCATGAGTGCGAGTCCTGGGAGTCCTGGGAGGGTGAGGATTAATGCCAGCCTGGGG AGCAGATAGCTGACAGAGTCCTTGGGTAACTGGCTTGAACCAGGACCTCAGGATTCC ACTCTGGGGATCTAGCTTTGTCTGGGCCAGTGAAGATCTCTATAATGGCATTATTGC CAGGGGATAAACATTTCACTGGGTTCTGATCTGTTGGGTGTGGCTTCCTGGAAAATA TGGTGAGAGGAATTCTGCTAAGGATACAGTTGATAAGAAAGTTCTGAGATTGATTAG TAATGCCTGCCTTGGACTCAGGAAGGGAAGTGGCAGTATGAATGCCATGTCTTAATC ATTTTGGTTAAAATATGCTTCCCAAAAGATTTCCACGTGTGTTCTTGTTTATTTGAC ATCTGTCTCCATATCAGTCTTGAAAGCCTTTCTGTGTGTATATATATGATGTTTGCG TGTATATATGTTTTTGTGTGTGCATATGGAAGTCAGAAATCACTGGGTGTCTTCCTC CATTCCTTTGCAATGTATGTTTTTTTTTTTTTTACGATTTATTTACTATATGAATGT TTTGCCTGAATACATGCATAGGTGTCACGTACATGCCTGCTGGAACGCTTGGAACTG GAGTTACAGGTGGCTATGAGCTACAGTGTGAGCACTGGGAATCAAACCTGGGTCTTC TGCAAGAGCAACAAATTAAAAGTCAGCTCTTAACTACTTGAGCTATTTTTCCAACTC C(SEQIDNO:63) >NP_083008.1V-typeimmunoglobulindomain-containing suppressorofT-cellactivationisoform1precursor[Mus musculus] MGVPAVPEASSPRWGTLLLAIFLAASRGLVAAFKVTTPYSLYVCPEGQNATLTCRIL GPVSKGHDVTIYKTWYLSSRGEVQMCKEHRPIRNFTLQHLQHHGSHLKANASHDQPQ KHGLELASDHHGNFSITLRNVTPRDSGLYCCLVIELKNHHPEQRFYGSMELQVQAGK GSGSTCMASNEQDSDSITAAALATGACIVGILCLPLILLLVYKQRQVASHRRAQELV RMDSSNTQGIENPGFETTPPFQGMPEAKTRPPLSYVAQRQPSESGRYLLSDPSTPLS PPGPGDVFFPSLDPVPDSPNSEAI(SEQIDNO:64) HumanB7-H7 >NM_007072.4HomosapiensHERV-HLTR-associating2 (HHLA2) (HHLA2),transcriptvariant1,mRNA AGTTCTCTTCAAGTCATGTAATCGACTTTTTTGAATTAGTTTTCAGTTTCATTTTGT TTTCCCTAATTCAAGTTGGGAACACTTCATTTTCCCCAATTCAAGTTGGGAACACTT CCTTGGTATTTCCTTGCTACATGGACTTTAGCAAATGCTACTTTACTCTCCTTCCAG CTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGTTACAGT GAGCCTTTTCCTAGTTTTACTGTTGGAAGCCTAACTCACAGGAGAGATTATGCAATA CAGTCCTGAAGTCAAGGGAGGAGAGCATGTAGGAGAATACTAACCCTGCACAGATTG TGATGGTGATGTGGAATATACTAAAGCCTAGAACGCACCTCCTCTGCATGACTAATA TGTTCTGCACAAGACATGAAGGCACAGACAGCACTGTCTTTCTTCCTCATTCTCATA ACATCTCTGAGTGGATCTCAAGGCATATTCCCTTTGGCTTTCTTCATTTATGTTCCT ATGAATGAACAAATCGTCATTGGAAGACTTGATGAAGATATAATTCTCCCTTCTTCA TTTGAGAGGGGATCCGAAGTCGTAATACACTGGAAGTATCAAGATAGCTATAAGGTT CACAGTTACTACAAAGGCAGTGACCATTTGGAAAGCCAAGATCCCAGATATGCAAAC AGGACATCCCTTTTCTATAATGAGATTCAAAATGGGAATGCGTCGCTATTTTTCAGA AGAGTAAGCCTTCTGGACGAAGGAATTTACACCTGCTATGTAGGAACAGCAATTCAA GTGATTACAAACAAAGTGGTGCTAAAGGTGGGAGTTTTTCTCACACCCGTGATGAAG TATGAAAAGAGGAACACAAACAGCTTCTTAATATGCAGCGTGTTAAGTGTTTATCCT CGTCCAATTATCACGTGGAAAATGGACAACACACCTATCTCTGAAAACAACATGGAA GAAACAGGGTCTTTGGATTCTTTTTCTATTAACAGCCCACTGAATATTACAGGATCA AATTCATCTTATGAATGTACAATTGAAAATTCACTGCTGAAGCAAACATGGACAGGG CGCTGGACGATGAAAGATGGCCTTCATAAAATGCAAAGTGAACACGTTTCACTCTCA TGTCAACCTGTAAATGATTATTTTTCACCAAACCAAGACTTCAAAGTTACTTGGTCC AGAATGAAAAGTGGGACTTTCTCTGTCCTGGCTTACTATCTGAGCTCCTCACAAAAT ACAATTATCAATGAATCCCGATTCTCATGGAACAAAGAGCTGATAAACCAGAGTGAC TTCTCTATGAATTTGATGGATCTTAATCTTTCAGACAGTGGGGAATATTTATGCAAT ATTTCTTCGGATGAATATACTTTACTTACCATCCACACAGTGCATGTAGAACCGAGC CAAGAAACAGCTTCCCATAACAAAGGCTTATGGATTTTGGTGCCCTCTGCGATTTTG GCAGCTTTTCTGCTGATTTGGAGCGTAAAATGTTGCAGAGCCCAGCTAGAAGCCAGG AGGAGCAGACACCCTGCTGATGGAGCCCAACAAGAAAGATGTTGTGTCCCTCCTGGT GAGCGCTGTCCCAGTGCACCCGATAATGGCGAAGAAAATGTGCCTCTTTCAGGAAAA GTATAGGAAATGAGAGAAGACTGTGACAACTCATGACCTGCATCCTTAATATCCAGT GACTTCATCTCCCCTTTCTTCACCACAATTCCAGGCAATGGCCTGTCGGAGCAGACA ATTCTACCACTGCAAAGAGTTGTAACCATTTTCTGGTATCACATTTATTTTTCAAGA CATACTTTTCAAGACATCATTCACTGACCCACTACCTGCATTGAGTATAAATGCCTG GATGTTAAGGATTCCAATTTAACTTTGAAAAGAACTGTCTCATTCATTTACATTTCT GTTACAGTCAGCCCAGGAGGTTACAGTGAGCTCTCCACTAAGAATCTGGAAGAAATG CATCACTAGGGGTTGATTCCCAATCTGATCAACTGATAATGGGTGAGAGAGCAGGTA AGAGCCAAAGTCACCTTAGTGGAAAGGTTAAAAACCAGAGCCTGGAAACCAAGATGA TTGATTTGACAAGGTATTTTAGTCTAGTTTTATATGAACGGTTGTATCAGGGTAACC AACTCGATTTGGGATGAATCTTAGGGCACCAAAGACTAAGACAGTATCTTTAAGATT GCTAGGGAAAAGGGCCCTATGTGTCAGGCCTCTGAGCCCAAGCCAAGCATCGCATCC CCTGTGATTTGCACGTATACATCCAGATGGCCTAAAGTAACTGAAGATCCACAAAAG AAGTAAAAATAGCCTTAACTGATGACATTCCACCATTGTGATTTGTTCCTGCCCCAC CCTAACTGATCAATGTACTTTGTAATCTCCCCCACCCTTAAGAAGGTACTTTGTAAT CTTCCCCACCCTTAAGAAGGTTCTTTGTAATTCTCCCCACCCTTGAGAATGTACTTT GTGAGATCCACCCTGCCCACAAAACATTGCTCTTAACTTCACCGCCTAACCCAAAAC CTATAAGAACTAATGATAATCCATCACCCTTCGCTGACTCTCTTTTCGGACTCAGCC CACCTGCACCCAGGTGAAATAAACAGCTTTATTGCTCACACAAA(SEQIDNO: 65) >NP_009003.1HERV-HLTR-associatingprotein2isoforma precursor[Homosapiens] MKAQTALSFFLILITSLSGSQGIFPLAFFIYVPMNEQIVIGRLDEDIILPSSFERGS EVVIHWKYQDSYKVHSYYKGSDHLESQDPRYANRTSLFYNEIQNGNASLFFRRVSLL DEGIYTCYVGTAIQVITNKVVLKVGVFLTPVMKYEKRNTNSFLICSVLSVYPRPIIT WKMDNTPISENNMEETGSLDSFSINSPLNITGSNSSYECTIENSLLKQTWTGRWTMK DGLHKMQSEHVSLSCQPVNDYFSPNQDFKVTWSRMKSGTFSVLAYYLSSSQNTIINE SRFSWNKELINQSDFSMNLMDLNLSDSGEYLCNISSDEYTLLTIHTVHVEPSQETAS HNKGLWILVPSAILAAFLLIWSVKCCRAQLEARRSRHPADGAQQERCCVPPGERCPS APDNGEENVPLSGKV(SEQIDNO:66 MouseBTNL1 >NM_001111094.1Musmusculusbutyrophilin-like1(Btnl1), mRNA ACCCTTAAATAAGAGCTGAAGATGGCTGCAGCTTTCTCCTAGACTCCTCCAGGAGAA ACTCTAAAGCCAGAGCCTGGGGGCAGCATTGTGTGTCCACCTTGCCACTGAGAACAT CTACGGAAATTGGACACTCTGGCCCCAGCATCCACACGCTTGACTGTTGGCCACAGT AACACAGGTGTGGATGGTCCCCAGAGCCAGGGTCCAGGAGTGCACTGAGGATCCCTG GGGCTTCAAGGAACCCACAGCTCTGTCCAGACGGGAATTTTTTTCCTGAGAACTTTC ACCTGTTGCCCTCCTATGGTGAACCTGGACTTGACCTTCCACTCTGATGATGAAGGG CTCCCCCTCCGTCCCTCCAGCTGGTTGTCTCCTCCCTCTGCTCCTCCTGCTGTTTAC CGGAGTCTCTGGAGAAGTGTCTTGGTTTTCTGTGAAGGGACCAGCTGAGCCCATCAC TGTCCTGCTGGGGACTGAAGCCACCCTGCCCTGCCAGCTGTCTCCTGAACAGAGTGC AGCTCGCATGCACATCCGATGGTACCGTGCCCAGCCCACCCCTGCTGTGCTGGTGTT CCACAACGGACAGGAGCAGGGAGAGGTGCAGATGCCGGAATACAGGGGCAGGACCCA GATGGTGAGACAAGCCATTGACATGGGAAGTGTGGCTCTGCAGATACAGCAGGTCCA GGCCTCTGATGATGGCCTGTACCACTGTCAGTTTACAGATGGCTTCACCTCCCAAGA GGTCTCCATGGAGCTTCGAGTCATAGGTTTAGGCTCTGCCCCTCTTGTTCACATGAC AGGACCTGAGAATGATGGGATCCGAGTGTTGTGCTCCTCAAGTGGCTGGTTCCCAAA ACCCAAAGTGCAATGGAGAGACACCTCCGGGAACATGCTACTGTCCTCCTCTGAGTT GCAGACCCAAGACAGAGAAGGGCTCTTCCAGGTGGAAGTGTCTCTTTTGGTCACAGA TAGAGCTATTGGCAATGTGATCTGCTCCATCCAAAATCCCATGTATGACCAGGAGAA ATCGAAGGCCATCCTCCTCCCAGAGCCCTTCTTCCCCAAGACGTGTCCATGGAAAGT AGCCCTGGTTTGTTCTGTCCTCATACTATTGGTCCTGCTCGGTGGGATCAGCCTTGG AATCTGGAAAGAACATCAAGTCAAAAGGAGAGAAATTAAAAAATGGTCAAAGGAACA TGAAGAAATGCTTCTGTTGAAGAAGGGGACAAAATCTGTACTGAAGATCAGAGATGA CCTCCAGGCCGACCTAGATCGGAGGAAGGCGCTGTACAAAGAAGACTGGAAGAAGGC CTTGCTGTACCCTGACTGGAGGAAGGAGCTGTTCCAGGAGGCTCCTGTGAGGATAAA TTATGAAATGCCTGACCAGGACAAGACAGACTCAAGGACAGAAGAGAACAGAGGTGA GGAGACTGTCAGCAGCTCACAAGTAGACCACAACCTCATCACACTCTCCCAGGAAGG CTTCATGTTGGGAAGATACTACTGGGAGGTGGATGTCAAGGACACAGAGGAGTGGAC ACTAGGAGTTTATGAGCTGTGCACTCAGGATGCATCACTTACAGACCCCTTGAGGAA ATTCAGAGTCCTGGAAAAGAATGGAGATGGATACAGGGCTCTTGACTTCTGTTCCCA AAACATTAATTCGGAAGAACCTCTGCAACTGAAGACACGTCCGCTGAAGATCGCCAT CTTCTTGGATCAGGAAGACAATGACCTCTCTTTCTACAACATGACCGATGAGACACA CATCTTTTCCTTTGCCCAGGTCCCTTTCTTGGGATCACCCTATCCTTACTTCACACG TAATTCCATGGGGCTCTCTGCAACAGCACAGCCCTAAGTGATGTGCACAGGGAATTC AATGGGTGGGTGCTGCAGCGTGCTACCCGTAAGGCCCTCTTAGGCAGGCACAGGGGG CCTCTGACCAAGAGGCCTCTTAACCTGAGACTCCATGAGCCTCGGGGATCAGATCCT GGACAAGATTCTCGGACCATCTGTGTCGTGCATGGTGTTATAGTTATTAATAGCCTT CCTTCTTTTGACAAAAATGTGTTTAATCATTCCTAAGATAAATGAATCCATGGCTTT CTGA(SEQIDNO:67) >NP_001104564.1butyrophilin-likeprotein1precursor [Musmusculus] MMKGSPSVPPAGCLLPLLLLLFTGVSGEVSWFSVKGPAEPITVLLGTEATLPCQLSP EQSAARMHIRWYRAQPTPAVLVFHNGQEQGEVQMPEYRGRTQMVRQAIDMGSVALQI QQVQASDDGLYHCQFTDGFTSQEVSMELRVIGLGSAPLVHMTGPENDGIRVLCSSSG WFPKPKVQWRDTSGNMLLSSSELQTQDREGLFQVEVSLLVTDRAIGNVICSIQNPMY DQEKSKAILLPEPFFPKTCPWKVALVCSVLILLVLLGGISLGIWKEHQVKRREIKKW SKEHEEMLLLKKGTKSVLKIRDDLQADLDRRKALYKEDWKKALLYPDWRKELFQEAP VRINYEMPDQDKTDSRTEENRGEETVSSSQVDHNLITLSQEGFMLGRYYWEVDVKDT EEWTLGVYELCTQDASLTDPLRKFRVLEKNGDGYRALDFCSQNINSEEPLQLKTRPL KIAIFLDQEDNDLSFYNMTDETHIFSFAQVPFLGSPYPYFTRNSMGLSATAQP (SEQIDNO:68) HumanVSIG8 >NM_001013661.1HomosapiensV-setandimmunoglobulin domaincontaining8(VSIG8),mRNA ACTCATTGCACCTTCCTGCCACCCCAGGCAGTGTCTGGGCCCTCAGCTCCCCCTCCC TCCACCTACCCCCTCACACCCACCACTACGACCCCACGGGATACCCAGCCCAGACGG AGGAAACACCGAGCCTAGAGACATGAGAGTTGGAGGAGCATTCCACCTTCTACTCGT GTGCCTGAGCCCAGCACTGCTGTCTGCTGTGCGGATCAACGGGGATGGACAGGAGGT CCTGTACCTGGCAGAAGGTGATAATGTGAGGCTGGGCTGCCCCTACGTCCTGGACCC TGAGGACTATGGTCCCAATGGGCTGGACATCGAGTGGATGCAGGTCAACTCAGACCC CGCCCACCACCGAGAGAACGTGTTCCTTAGTTACCAGGACAAGAGGATCAACCATGG CAGCCTTCCCCATCTGCAGCAGAGGGTCCGCTTTGCAGCCTCAGACCCAAGCCAGTA CGATGCCTCCATCAACCTCATGAACCTGCAGGTATCTGATACAGCCACTTATGAGTG CCGGGTGAAGAAGACCACCATGGCCACCCGGAAGGTCATTGTCACTGTCCAAGCACG ACCTGCAGTGCCCATGTGCTGGACAGAGGGCCACATGACATATGGCAACGATGTGGT GCTGAAGTGCTATGCCAGTGGGGGCTCCCAGCCCCTCTCCTACAAGTGGGCCAAGAT CAGTGGGCACCATTACCCCTATCGAGCTGGGTCTTACACCTCCCAGCACAGCTACCA CTCAGAGCTGTCCTACCAGGAGTCCTTCCACAGCTCCATAAACCAAGGCCTGAACAA TGGGGACCTGGTGTTGAAGGATATCTCCAGAGCAGATGATGGGCTGTATCAGTGCAC AGTGGCCAACAACGTGGGCTACAGTGTTTGTGTGGTGGAGGTGAAGGTCTCAGACTC CCGGCGTATAGGCGTGATCATCGGCATCGTCCTGGGCTCTCTGCTCGCGCTGGGCTG CCTGGCCGTAGGCATCTGGGGGCTCGTCTGCTGCTGCTGCGGGGGCTCCGGGGCTGG CGGCGCCCGCGGTGCCTTCGGCTACGGCAACGGCGGCGGGGTCGGCGGAGGGGCCTG CGGCGACTTGGCTAGTGAGATCAGAGAGGACGCCGTGGCGCCCGGGTGCAAGGCCAG CGGGCGCGGCAGCCGCGTCACCCACCTCCTGGGGTACCCGACGCAGAACGTCAGCCG CTCCCTGCGCCGCAAGTACGCGCCTCCCCCCTGCGGCGGCCCCGAGGACGTGGCCCT GGCGCCCTGCACCGCCGCCGCCGCCTGCGAAGCGGGCCCCTCCCCGGTCTACGTCAA GGTCAAGAGCGCGGAGCCGGCTGACTGCGCCGAGGGGCCGGTGCAGTGCAAGAACGG CCTCTTGGTGTGAGCGCGCGCGCCGGGCCGGGCTGCGCCCCAGCCAGGAGGAGGGCG CGGGGCTCTCTGTCTGCAGCTGGGGACACGTCGGGGCTGGGGACGACCTCGCTCGCC CCAGGCTGCCAGGCGGCTGGGGGTGAAGGCATTTCCCTAAGGAAATGCGTAGGGAGG CAGAGCCTCCTCCCCAAAAGTGGGAAGGGGCGGGCGAGGGCGGAGGAAGGCGATCCT GAGCCTTCTCCGCACCCCCGGGACCGAAGGCTTGGGGGAGAGGGAGGGAGGAGGAGG CTGAGTGTCCTAGAGCGGCTGAGGCCGGAGGCCTGGTGTCCCCAGCCTAAGCAGAGG GCCCCGGGGGCCGGGTGGGTGGGGGTCTGTCTGGACGAATTGTTCTGTGTGTGAGGT CTGAGCTCTGAGGCAGCAGTGTTAGCACAATAAAGAAACATTGAGACGTGA(SEQ IDNO:69) >NP_001013683.1V-setandimmunoglobulindomain- containingprotein8precursor[Homosapiens] MRVGGAFHLLLVCLSPALLSAVRINGDGQEVLYLAEGDNVRLGCPYVLDPEDYGPNG LDIEWMQVNSDPAHHRENVFLSYQDKRINHGSLPHLQQRVRFAASDPSQYDASINLM NLQVSDTATYECRVKKTTMATRKVIVTVQARPAVPMCWTEGHMTYGNDVVLKCYASG GSQPLSYKWAKISGHHYPYRAGSYTSQHSYHSELSYQESFHSSINQGLNNGDLVLKD ISRADDGLYQCTVANNVGYSVCVVEVKVSDSRRIGVIIGIVLGSLLALGCLAVGIWG LVCCCCGGSGAGGARGAFGYGNGGGVGGGACGDLASEIREDAVAPGCKASGRGSRVT HLLGYPTQNVSRSLRRKYAPPPCGGPEDVALAPCTAAAACEAGPSPVYVKVKSAEPA DCAEGPVQCKNGLLV(SEQIDNO:70) MouseVSIG8 >NM_177723.4MusmusculusV-setandimmunoglobulindomain containing8(Vsig8),transcriptvariant1,mRNA ACTCATTGCATCTTCCTGCCACCCCGGGCAGTGTCTGGGCCCTCCGCTCCCCCTCCC TCCACCTGCCCCTTCCACCCACCACCACCAGCCCACTGGAGCCCAGCTCAGGCGGAG GAAAGACCAAGCCTAGAGACATGGGAGTTCGAGGAGCACTCCATCTTCTACTTGTGT GCCTGAGCCCAGCACTGTTGTCTGCTGTAAGGATCAACGGGGATGGCCAGGAGGTCA TGTACCTGGCAGAAGGTGACAATGTGAGGCTAGGCTGTCCCTACCTCCTGGATCCTG AGGATTTGGGTACCAACAGTCTGGACATTGAGTGGATGCAAGTCAACTCAGAGCCCT CACACAGGGAGAATGTTTTTCTTACTTATCAAGACAAGAGGATAGGTCATGGCAACC TCCCCCATCTGCAGCAGAGGGTCCGCTTTGCAGCCTCAGACCCCAGCCAGTACGATG CCTCCATCAACCTCATGAACCTGCAGGTATCTGACACAGCAACCTATGAGTGCCGGG TGAAGAAGACCACCATGGCCACCAGGAAGGTCATTGTCACTGTCCAAGCACGTCCTG CGGTGCCCATGTGTTGGACGGAAGGCCACATGTCAAAGGGCAACGATGTGGTGCTGA AGTGCTTTGCCAACGGAGGCTCTCAGCCCCTCTCCTACAAGTGGGCCAAGATCAGTG GGCACAGTCACCCCTACCGAGCTGGGGCTTACCACTCACAGCACAGCTTCCACTCTG AGCTTTCTTACCAAGAGTCATTCCACAGCACCATCAACCAAGGCCTGGGCAACGGAG ACCTGCTGTTGAAGGGCATCAACGCAGACGACGATGGGCTGTATCAGTGCACAGTGG CCAACCATGTGGGCTACAGCGTCTGTGTGGTAGAGGTGAAAGTCTCAGACTCCCAGC GAGTAGGCATGATCGTTGGAGCAGTGCTGGGCTCTTTGCTCATGCTGGCCTGCCTGG CACTAGGCATCTGGGGGCTCATCTGCTGCTGCTGCGGAGGCGGCGGGGCCGGTGGTG CCCGAGGTGCCTTCGGCTACGGGGTCGGCGGCGGGGTCGGCGGAGGGGCCTGCGGCG ACTTGGCTAGTGAGATCAGAGTGGACGCCGAGGCGCCCGGGTGTAAGGCCAGCGGGC GCGGCAGCCGCGTCACCCACCTCCTGGGGTACCCGACGCAGAACGTCAGCCGCTCCC TGCGCCGCAAGTACGCGCCTCCGCCCTGCGGCGGCCCCGAGGACGTGGCCCTAGTGC CCCGCACCGCCTCCGCCTCCTGCGAAGCGGGTCCCTCCCCCGTCTACATCAAGGTCA AGAGCGCGGAGCCGGCCGACTGCGCCGACTGTGCCCAGGTCGAGCAGCGCTCGTGCA AGGACGGCCTCTTAGTGTGAGCGCACAGCACCGGGCTGCGCCCCGGCTGGGAGGTGG TTCGGGGGCTCTCTGCCCGCAGCTGGGGACAGGTTCGGGCCAGCAGACCTGGCTCTC TCATTGGCCACCTAGCGGTGGTAAGGAAATTTCCCTCTGAGAAGCCAAGCCGGGCAG ACCCTCCTCCCCTGTAGTGGGAGGAGAGGCGGGGGAGACAGAAAACAGTTCAGAGCT CTCCCTCACCCCTGGTTTCCAGGGAGAGGAAGGGAGAGGAGAGCTGTCGGTATCCCA GAACCGCAGAGGTACAACCCAGATGTCCCCAGCCAAGGCGAGGGCCCCCCAGCCCTG GGTAGGTGGATGTCAGGGCTGAATTGCTCTGTGTGTGAGATCTGAGCTCCAAGGCAA CAGTGTTAGCACAATAAAGAAACTTAAAGACTGAAAAAAAAAAAAAA(SEQID NO:71) >NP_808391.2V-setandimmunoglobulindomain-containing protein8precursor[Musmusculus] MGVRGALHLLLVCLSPALLSAVRINGDGQEVMYLAEGDNVRLGCPYLLDPEDLGTNS LDIEWMQVNSEPSHRENVFLTYQDKRIGHGNLPHLQQRVRFAASDPSQYDASINLMN LQVSDTATYECRVKKTTMATRKVIVTVQARPAVPMCWTEGHMSKGNDVVLKCFANGG SQPLSYKWAKISGHSHPYRAGAYHSQHSFHSELSYQESFHSTINQGLGNGDLLLKGI NADDDGLYQCTVANHVGYSVCVVEVKVSDSQRVGMIVGAVLGSLLMLACLALGIWGL ICCCCGGGGAGGARGAFGYGVGGGVGGGACGDLASEIRVDAEAPGCKASGRGSRVTH LLGYPTQNVSRSLRRKYAPPPCGGPEDVALVPRTASASCEAGPSPVYIKVKSAEPAD CADCAQVEQRSCKDGLLV(SEQIDNO:72) HumanVSIG3 >NM_001015887.3Homosapiensimmunoglobulinsuperfamily (IGSF11) member11(IGSF11),transcriptvariant2,mRNA AGTCCTGGGGCAGGGCTGGGTGGCACGGCTGGCGAGCCCGGAACGCCTCTGGTCACA GCTCAGCGTCCGCGGAGCCGGGCGGCGCTGCAGCTGCACTTGGCTCGTCTGTGGGTC TGACAGTCCCAGCTCTGCGCGGGGAACAGCGGCCCGGCGCTGGGTGTGGGAGGACCA GGCTGCCCCAAGAGCGCGGAGACTCACGCCCGCTCCTCTCCTGTTGCGACCGGGAGC CGGGTAGGAGGCAGGCGCGCTCCCTGCGGCCCCGGGATGACTTCTCAGCGTTCCCCT CTGGCGCCTTTGCTGCTCCTCTCTCTGCACGGTGTTGCAGCATCCCTGGAAGTGTCA GAGAGCCCTGGGAGTATCCAGGTGGCCCGGGGTCAGCCAGCAGTCCTGCCCTGCACT TTCACTACCAGCGCTGCCCTCATTAACCTCAATGTCATTTGGATGGTCACTCCTCTC TCCAATGCCAACCAACCTGAACAGGTCATCCTGTATCAGGGTGGACAGATGTTTGAT GGTGCCCCCCGGTTCCACGGTAGGGTAGGATTTACAGGCACCATGCCAGCTACCAAT GTCTCTATCTTCATTAATAACACTCAGTTATCAGACACTGGCACCTACCAGTGCCTG GTCAACAACCTTCCAGACATAGGGGGCAGGAACATTGGGGTCACCGGTCTCACAGTG TTAGTTCCCCCTTCTGCCCCACACTGCCAAATCCAAGGATCCCAGGATATTGGCAGC GATGTCATCCTGCTCTGTAGCTCAGAGGAAGGCATTCCTCGACCAACTTACCTTTGG GAGAAGTTAGACAATACCCTCAAACTACCTCCAACAGCTACTCAGGACCAGGTCCAG GGAACAGTCACCATCCGGAACATCAGTGCCCTGTCTTCAGGTTTGTACCAGTGCGTG GCTTCTAATGCTATTGGAACCAGCACCTGTCTTCTGGATCTCCAGGTTATTTCACCC CAGCCCAGGAACATTGGACTAATAGCTGGAGCCATTGGCACTGGTGCAGTTATTATC ATTTTTTGCATTGCACTAATTTTAGGGGCATTCTTTTACTGGAGAAGCAAAAATAAA GAGGAGGAAGAAGAAGAAATTCCTAATGAAATAAGAGAGGATGATCTTCCACCCAAG TGTTCTTCTGCCAAAGCATTTCACACTGAGATTTCCTCCTCGGACAACAACACACTA ACCTCTTCCAATGCCTACAACAGTCGATACTGGAGCAACAATCCAAAAGTTCATAGA AACACAGAGTCAGTCAGCCACTTCAGTGACTTGGGCCAATCTTTCTCTTTCCACTCA GGCAATGCCAACATACCATCCATTTATGCTAATGGGACCCATCTGGTCCCGGGTCAA CATAAGACTCTGGTAGTGACAGCCAACAGAGGGTCATCACCACAGGTGATGTCCAGG AGCAATGGCTCAGTCAGTAGGAAGCCTCGGCCTCCACACACTCATTCCTACACCATC AGCCACGCAACACTGGAACGAATTGGTGCAGTACCTGTCATGGTACCAGCCCAGAGT CGGGCCGGGTCCTTGGTATAGGACATGAGGAAATGTTGTGTTCAGAAATGAATAAAT GGAATGCCCTCATACAAGGGGGAGGGTGGGGTGGGGAGTGCTGGGAAAGAAACACTT CCTTATAATTATATTAGTAAAATGCACAAAGAAGAAGGCAGTGCTGTTACTTGGCCA CTAAGATGTGTAAAATGGACTGAAATGCTCCATCATGAAGACTTGCTTCCCCACCAA AGATGTCCTGGGATTCTGCTGGATCTCAAAGATGTGCCAAGCCAAGGAAAAAGATAC AAGAGCAGAATAGTACTTAAAATCCAAACTGCCGCCCAGATGGGCTTGTTCTTCATG CCTAACTTAATAATTTTTAAGAGATTAAAGTGCCAGATGGAGTTTAAATATTGAAAT TATTTTAAAAGGTAGGTGTCTTTAAGAAAATAACAAGCAACCCTGTGATATGTTCCG TCTCTCCCAATTCCCTCGTTATATAGAGGGCTTAATGGTATAAATGGTTAATATTGG TCCCAACAGGGCTGACTCTTCTATCATATAATCAAAACTTTTTACATGAGCAAAATT CAGTAAGAAATGGGGGAAGACAAAGGAAACGTCTTTGAGAAGCCCCTTCATATTTAT TTATTTATCTCTTCCTGAACCATGAATTTCATATGTGGAATATTGCTATATTGACAG ATTCTTGCCTGTCTGTGTTATTCTAGGATCTGTTACAGGTCCATGGCAATTACTGTT TATTTTTTCCTGGAAAAATATTTTTTTATAAAAGGCTTTTTTTTTTTTTTAAATACA TGAGAGGCATTGGGCTAAGAAAGAAAAGACTGTTGTATAATACCTTGTTCAATGGTT GTATTTAGTGAGCTCATAGAGGTCCATCATATCATGACCGAGCTAGGTTGTGTGGGC AGGAAGGTAGGGCTAAGGGGTTGTAGCCTTGCTGGGCAGCCTCTCAGAGCAAGGTTG TTCAGATCTCCCTTGCTATTACAGTAGGTTACTATTAATGAGGGCAGCACCTGATGC CTTTTGTACTGAGGTATGTAACTTTCTCCTTATTTGACAAGTAGAAGTTAACTTACT TGTCAGGGAGGGCAGACGTTTTTTTGTTCTGTTTCGTTTTTCAAAATAATGCTTTTT GCAAAAGAGGTAAGACTGAGACTAAAGGTGTTATCTTCTGGTGTGCTCCTGGAAGTG TCTACCCTACATTTGTGTCAGCTCAGGGTTGCAGTGTTGCCCAGATGCATTTTACAT CACTGTAAAGAGATTACTTTTGTGGTTACTACCTGGCTTGGCTGGCCTTGCGGTTCA CCAGATTAATTTACAAACTCCCCCACTTTATTTTGTGCTATGTAGATCTGGCCATAC TTGCATTAGTGACTGTCTTGCCTTAACCACACTTAAGCAACCCACAAATTTCTTCTC AGATTTGTTTCCTAGATTACTTATGATACTCATCCCATGTCTCAATAAGAGTGTCTT TTCTTTCTGGATGTGTTCTCTTACTCCCTCTTACCACCATACTTTTTGCTCTCTTCT CCTGCAAGCGTAGTCTTCACAGGGAGTGGCTTCCTGACATTTTTTTCAGTTATGTGA ATGAATGGAAACCAACAGCTGCTGCAAACACTGTTTTTCCAAGAAGGCTACACTCAG AACCTAACCATTGCCAACCATTTCAGTATTGATAAAAAGCTGAATTTACTTTAGCAT TACTTATTTTTTTTTCCATTTGATGGTTCTTACTTTGTAAAAATTTAAATAAATGAA TGTCTATACTTTTTATAAAGAAAAGTGAAAATACCATGACACTGAAAAGATGATGCT ATCAGATGCTGTTTAGAAAGCATTTATCTTGCATTTCTTTATTCTTTCTAATTATCT AAAATTCAATAAAATTTTATTCATATAAAATAAGTTGTCATTAATTATCAATACTAA CGAGTATGTCATTTTAAAACTTAGTATTCTCTTTAATGTTACAAGA(SEQID NO:73) >NP_001015887.1immunoglobulinsuperfamilymember11 isoformbprecursor[Homosapiens] MTSQRSPLAPLLLLSLHGVAASLEVSESPGSIQVARGQPAVLPCTFTTSAALINLNV IWMVTPLSNANQPEQVILYQGGQMFDGAPRFHGRVGFTGTMPATNVSIFINNTQLSD TGTYQCLVNNLPDIGGRNIGVTGLTVLVPPSAPHCQIQGSQDIGSDVILLCSSEEGI PRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLL DLQVISPQPRNIGLIAGAIGTGAVIIIFCIALILGAFFYWRSKNKEEEEEEIPNEIR EDDLPPKCSSAKAFHTEISSSDNNTLTSSNAYNSRYWSNNPKVHRNTESVSHFSDLG QSFSFHSGNANIPSIYANGTHLVPGQHKTLVVTANRGSSPQVMSRSNGSVSRKPRPP HTHSYTISHATLERIGAVPVMVPAQSRAGSLV(SEQIDNO:74) MouseVSIG3 >NM_170599.2Musmusculusimmunoglobulinsuperfamily, (IGSF11) member11(Igsf11),mRNA CGGCTGGTGGTGGCCGCGGCGGCCGGCGAGCCCGGGACGCCCGAGCCTGCCCCGAGC CTCGGCGGAGCGGAGTGGCCTCGGCGCTCCCGTGTCCCGCTTGGTCCCACGCTGCAC CCCGCCGCCCAGGAGCCCGGCGGACGGCGGCTCCCCCGGCGGCTCCGGCATGACTCG GCGGCGCTCCGCTCCGGCGTCCTGGCTGCTCGTGTCGCTGCTCGGTGTCGCAACATC CCTGGAAGTGTCCGAGAGCCCAGGCAGTGTCCAGGTGGCCCGGGGCCAGACAGCAGT CCTGCCCTGCGCCTTCTCCACCAGTGCTGCCCTCCTGAACCTCAATGTCATTTGGAT GGTCATTCCCCTCTCCAATGCAAACCAGCCCGAACAGGTCATTCTTTATCAGGGTGG ACAAATGTTTGACGGCGCCCTCCGGTTCCACGGGAGGGTAGGATTTACCGGCACCAT GCCTGCTACCAATGTCTCGATCTTCATCAATAACACACAGCTGTCAGATACGGGCAC GTACCAGTGCTTGGTGAATAACCTTCCAGACAGAGGGGGCAGAAACATCGGGGTCAC TGGCCTCACAGTGTTAGTCCCCCCTTCTGCTCCACAATGCCAAATCCAAGGATCCCA GGACCTCGGCAGTGACGTCATCCTTCTGTGTAGTTCAGAGGAAGGCATCCCTCGGCC CACGTACCTTTGGGAGAAGTTAGATAATACGCTCAAGCTACCTCCAACAGCCACTCA GGACCAGGTCCAGGGAACAGTCACCATCCGGAATATCAGTGCCCTCTCTTCCGGTCT GTACCAGTGTGTGGCTTCTAATGCCATCGGGACCAGCACCTGTCTGCTGGACCTCCA GGTTATCTCACCCCAGCCCCGGAGCGTTGGAGTAATAGCCGGAGCGGTTGGCACCGG TGCTGTTCTTATCGTCATCTGCCTTGCACTAATTTCAGGGGCGTTCTTTTACTGGAG AAGCAAAAACAAAGAGGAGGAGGAGGAAGAAATTCCTAATGAAATCAGAGAGGATGA TCTTCCCCCTAAATGCTCTTCTGCCAAAGCCTTCCACACGGAGATATCCTCCTCAGA AAATAACACGCTGACCTCTTCCAATACCTACAACAGTCGATACTGGAACAACAATCC AAAACCCCATAGAAACACAGAGTCTTTCAACCACTTCAGTGACTTACGCCAGTCTTT CTCTGGCAATGCAGTTATCCCATCAATCTATGCAAATGGGAACCATCTGGTTTTGGG TCCACATAAGACTCTGGTAGTTACAGCCAACAGAGGGTCATCACCTCAGGTCTTGCC CAGGAACAATGGTTCAGTCAGCAGGAAGCCTTGGCCTCAACACACTCATTCCTACAC AGTAAGCCAAATGACCCTGGAGCGCATCGGTGCAGTGCCTGTCATGGTGCCTGCCCA GAGTCGAGCAGGGTCCCTGGTATAGGATGACTGAGGAAACCATGTTCAGAAGAGAAT AAATGGACCGCCTTCAGGCAAGGGGGGAGCACTGCCTTCAGGCAAGGGGGGAGCACT GCCTTCAGGCAAGAGGGAGAGTGGGATGGGTGAGTGCTGAAAAATAAACTTTTGTTA CGATTCCATTAGCAAAAAGCACAAAGAGGAGGCGTGTGTGAAGTGGCCTGGGGTTGT TCCATAATGAAGACTCAAGAAGACTGTTTCCCCACCACAGATGTCCTGAGATTCAGT TAAAACGAAACATGCTGCATCTCCAGAGATGTGCCAAGCCAAGGAGAATGCTAGAAG CAGAGTAAAGCTTACCCCCCAAACTGTGGTCCAGCTGGACCCCTTCTTTAATTCTTG CCTAACTTAATTATTTTCAGGACCCTTCAAGTGCCAGGTGGAATTTACATAATGAAA TTATTTTTTAAAAATAGGTGTCCTTAGGGAGAGAAAACAGGAGCAAGCTCATGGTCT GGCCTAGTCTCCCTCTCCCACTCCTTCTGATGACACTAGCAATGCATTCCATCTGAC CTGACTTTATCATAGAGGCAAAATTGTTCAGAACACTGGCTGGAGATGGGGAGAAAT AAGGAAACTTCTTGTGAACACCCTACACACACACACACACACACACACACACACACA CACACACACACACACACACACACACACACATTTATTTACCTCCTCCTGAACCATGAA TCGTATTGGTGATTTTGCTATATTGACAGATTCTCATCTGTTACACTCTAGGATCTC TCACAGGTCTGTGGCAATTACTGTTCATGATTTCCTGAAAAAATATTTTTTTAAAAG AAAACTATTTTTTTTAAATACTAGAGAGACAGTGGACTAGGAAAGCGAGAACTTGCC GCCTTGTCTAGTGACTGTATTCAATGACTGAACAGAGGCCCCCCCCACCATACAAGA GTTTTAGGTGATTGAGTGGGTGGAACCAGCTGGAGCCAGGTGGGAGGGGCCTTTACA TTGCCAGCAGGGCCCCAAAGAATTGAGATTGTGTATGGCAACCGTTAATGAGGACAG CGCCTGATGCCTTTTGTACCGAGGAAGATAATTGCCTCTTGTTTGACAAGTAGAGTT TAGTAGGTTATTACAAAAAGGGCAAGAGTTGTTTTGGTTTTGTTTCTTTCAAAATAA TTTTTTTTCAAAAGAATAACAAGGGTTAGGCAAATGGGGGACCTTCCTGTGTGCTCT TGGGGGTCTGCTCAGCATCTGGAAATTTGGGTGTGCGATTTTCCCTGAACACATTGC ATACCAGTGTAAAAAGACTCTGCCTCCCCCCTTTTTGGCTTTTTTACTGGGCTTGGC TGGCCTTGCAGTTTACCAGATTCATTTACAGACTCTCTGCTCTGTATGGCGCCGCCT GCCATGTCTGTCTTGGTGACTATCCTGCCTTAATCACTTTGCTTTAGGGCAACTCAT GGTGATCTCTTCCAAGATCTGTTTTTAAATTGTTTGGACTACTTGAGCCACAACTCT CAGAGGACATTCCTTTTTTTTTTTTTTTTTTTTTCTCCTTTCTTCCATTGCTTTGTC CCTCTTCCCCTGTGCTTCCTGCCTTCTTTCCCTGTCCCATGGGCACAGTCCTCACAG GGAGTGGCCTCCTCTCTCCAGTGATGTAAGTGAATGGAAGCCATCACTGGCTGCACA TACCTTTTTCAAAAGGGACACTCGGGAAGTCACTGCTGTGACCGTTTCGATGTTGAT AAGAAGGTGAATTTACTGTAGTGTTACCACCTTCTCCCCACTTGATGGTTCTTGACT TTGTAAAAATTTAAATAAATGAATGTCTATACTTTTTAAGGAAAAGAGAAAATACCA TGTCACAGAAAAGGTGAAACTATTAGATGCTGTTTAGAAAGCATTTATCTTGCATTT CTTTATTCTTTCTAATTACCTAAAATTCAATAAAAGTTTATTCATATAAAAAAAAAA AAAAAAAAAA(SEQIDNO:75) >NP_733548.2immunoglobulinsuperfamilymember11 precursor[Musmusculus] MTRRRSAPASWLLVSLLGVATSLEVSESPGSVQVARGQTAVLPCAFSTSAALLNLNV IWMVIPLSNANQPEQVILYQGGQMFDGALRFHGRVGFTGTMPATNVSIFINNTQLSD TGTYQCLVNNLPDRGGRNIGVTGLTVLVPPSAPQCQIQGSQDLGSDVILLCSSEEGI PRPTYLWEKLDNTLKLPPTATQDQVQGTVTIRNISALSSGLYQCVASNAIGTSTCLL DLQVISPQPRSVGVIAGAVGTGAVLIVICLALISGAFFYWRSKNKEEEEEEIPNEIR EDDLPPKCSSAKAFHTEISSSENNTLTSSNTYNSRYWNNNPKPHRNTESFNHFSDLR QSFSGNAVIPSIYANGNHLVLGPHKTLVVTANRGSSPQVLPRNNGSVSRKPWPQHTH SYTVSQMTLERIGAVPVMVPAQSRAGSLV(SEQIDNO:76) HumanVSIG4 >NM_007268.3HomosapiensV-setandimmunoglobulindomain containing4(VSIG4),transcriptvariant1,mRNA ACAGACGCTGGCGGCCACCAGAAGTTTGAGCCTCTTTGGTAGCAGGAGGCTGGAAGA AAGGACAGAAGTAGCTCTGGCTGTGATGGGGATCTTACTGGGCCTGCTACTCCTGGG GCACCTAACAGTGGACACTTATGGCCGTCCCATCCTGGAAGTGCCAGAGAGTGTAAC AGGACCTTGGAAAGGGGATGTGAATCTTCCCTGCACCTATGACCCCCTGCAAGGCTA CACCCAAGTCTTGGTGAAGTGGCTGGTACAACGTGGCTCAGACCCTGTCACCATCTT TCTACGTGACTCTTCTGGAGACCATATCCAGCAGGCAAAGTACCAGGGCCGCCTGCA TGTGAGCCACAAGGTTCCAGGAGATGTATCCCTCCAATTGAGCACCCTGGAGATGGA TGACCGGAGCCACTACACGTGTGAAGTCACCTGGCAGACTCCTGATGGCAACCAAGT CGTGAGAGATAAGATTACTGAGCTCCGTGTCCAGAAACTCTCTGTCTCCAAGCCCAC AGTGACAACTGGCAGCGGTTATGGCTTCACGGTGCCCCAGGGAATGAGGATTAGCCT TCAATGCCAGGCTCGGGGTTCTCCTCCCATCAGTTATATTTGGTATAAGCAACAGAC TAATAACCAGGAACCCATCAAAGTAGCAACCCTAAGTACCTTACTCTTCAAGCCTGC GGTGATAGCCGACTCAGGCTCCTATTTCTGCACTGCCAAGGGCCAGGTTGGCTCTGA GCAGCACAGCGACATTGTGAAGTTTGTGGTCAAAGACTCCTCAAAGCTACTCAAGAC CAAGACTGAGGCACCTACAACCATGACATACCCCTTGAAAGCAACATCTACAGTGAA GCAGTCCTGGGACTGGACCACTGACATGGATGGCTACCTTGGAGAGACCAGTGCTGG GCCAGGAAAGAGCCTGCCTGTCTTTGCCATCATCCTCATCATCTCCTTGTGCTGTAT GGTGGTTTTTACCATGGCCTATATCATGCTCTGTCGGAAGACATCCCAACAAGAGCA TGTCTACGAAGCAGCCAGGGCACATGCCAGAGAGGCCAACGACTCTGGAGAAACCAT GAGGGTGGCCATCTTCGCAAGTGGCTGCTCCAGTGATGAGCCAACTTCCCAGAATCT GGGCAACAACTACTCTGATGAGCCCTGCATAGGACAGGAGTACCAGATCATCGCCCA GATCAATGGCAACTACGCCCGCCTGCTGGACACAGTTCCTCTGGATTATGAGTTTCT GGCCACTGAGGGCAAAAGTGTCTGTTAAAAATGCCCCATTAGGCCAGGATCTGCTGA CATAATTGCCTAGTCAGTCCTTGCCTTCTGCATGGCCTTCTTCCCTGCTACCTCTCT TCCTGGATAGCCCAAAGTGTCCGCCTACCAACACTGGAGCCGCTGGGAGTCACTGGC TTTGCCCTGGAATTTGCCAGATGCATCTCAAGTAAGCCAGCTGCTGGATTTGGCTCT GGGCCCTTCTAGTATCTCTGCCGGGGGCTTCTGGTACTCCTCTCTAAATACCAGAGG GAAGATGCCCATAGCACTAGGACTTGGTCATCATGCCTACAGACACTATTCAACTTT GGCATCTTGCCACCAGAAGACCCGAGGGAGGCTCAGCTCTGCCAGCTCAGAGGACCA GCTATATCCAGGATCATTTCTCTTTCTTCAGGGCCAGACAGCTTTTAATTGAAATTG TTATTTCACAGGCCAGGGTTCAGTTCTGCTCCTCCACTATAAGTCTAATGTTCTGAC TCTCTCCTGGTGCTCAATAAATATCTAATCATAACAGCAA(SEQIDNO:77) >NP_009199.1V-setandimmunoglobulindomain-containing protein4isoform1precursor[Homosapiens] MGILLGLLLLGHLTVDTYGRPILEVPESVTGPWKGDVNLPCTYDPLQGYTQVLVKWL VQRGSDPVTIFLRDSSGDHIQQAKYQGRLHVSHKVPGDVSLQLSTLEMDDRSHYTCE VTWQTPDGNQVVRDKITELRVQKLSVSKPTVTTGSGYGFTVPQGMRISLQCQARGSP PISYIWYKQQTNNQEPIKVATLSTLLFKPAVIADSGSYFCTAKGQVGSEQHSDIVKF VVKDSSKLLKTKTEAPTTMTYPLKATSTVKQSWDWTTDMDGYLGETSAGPGKSLPVF AIILIISLCCMVVFTMAYIMLCRKTSQQEHVYEAARAHAREANDSGETMRVAIFASG CSSDEPTSQNLGNNYSDEPCIGQEYQIIAQINGNYARLLDTVPLDYEFLATEGKSVC (SEQIDNO:78) MouseVSIG4 >NM_177789.5MusmusculusV-setandimmunoglobulindomain containing4(Vsig4),mRNA AGCTACCAGCACTTCCAGGTTCTTCAGCAGCAAGAGGATGGAAGGATGAATAGAAGT AGCTTCAAATAGGATGGAGATCTCATCAGGCTTGCTGTTCCTGGGCCACCTAATAGT GCTCACCTATGGCCACCCCACCCTAAAAACACCTGAGAGTGTGACAGGGACCTGGAA AGGAGATGTGAAGATTCAGTGCATCTATGATCCCCTGAGAGGCTACAGGCAAGTTTT GGTGAAATGGCTGGTAAGACACGGCTCTGACTCCGTCACCATCTTCCTACGTGACTC CACTGGAGACCATATCCAGCAGGCAAAGTACAGAGGCCGCCTGAAAGTGAGCCACAA AGTTCCAGGAGATGTGTCCCTCCAAATAAATACCCTGCAGATGGATGACAGGAATCA CTATACATGTGAGGTCACCTGGCAGACTCCTGATGGAAACCAAGTAATAAGAGATAA GATCATTGAGCTCCGTGTTCGGAAATATAATCCACCTAGAATCAATACTGAAGCACC TACAACCCTGCACTCCTCTTTGGAAGCAACAACTATAATGAGTTCAACCTCTGACTT GACCACTAATGGGACTGGAAAACTTGAGGAGACCATTGCTGGTTCAGGGAGGAACCT GCCAATCTTTGCCATAATCTTCATCATCTCCCTTTGCTGCATAGTAGCTGTCACCAT ACCTTATATCTTGTTCCGCTGCAGGACATTCCAACAAGAGTATGTCTATGGAGTGAG CAGGGTGTTTGCCAGGAAGACAAGCAACTCTGAAGAAACCACAAGGGTGACTACCAT CGCAACTGATGAACCAGATTCCCAGGCTCTGATTAGTGACTACTCTGATGATCCTTG CCTCAGCCAGGAGTACCAAATAACCATCAGATCAACAATGTCTATTCCTGCCTGCTG AACACAGTTTCCAGAAACTAAGAAGTTCTTGCTACTGAAGAAAATAACATCTGCTAA AATGCCCCTACTAAGTCAAGGTCTACTGGCGTAATTACCTGTTACTTATTTACTACT TGCCTTCAACATAGCTTTCTCCCTGGCTTCCTTTCTTCTTAGACAACCTAAAGTATC TATCTAGTCTGCCAATTCTGGGGCCATTGAGAAATCCTGGGTTTGGCTAAGAATATA CTACATGCACCTCAAGAAATCTAGCTTCTGGGCTTCACCCAGAACAATTTTCTTCCT AGGGCCTTCACAACTCTTCTCCAAACAGCAGAGAAATTCCATAGCAGTAGAGGTTCT TTATCATGCCTCCAGACAGCGTGAGTCTCAGTCCTACAAACTCAGACAAGCACATGG GTCTAGGATTACTCCTCTTTCTCTAGGGCCAGATGACTTTTAATTGATATTACTATT GCTACATTATGAATCTAATGCACATGTATTCTTTTGTTGTTAATAAATGTTTAATCA TGACATCAA(SEQIDNO:79) >NP_808457.1V-setandimmunoglobulindomain-containing protein4precursor[Musmusculus] MEISSGLLFLGHLIVLTYGHPTLKTPESVTGTWKGDVKIQCIYDPLRGYRQVLVKWL VRHGSDSVTIFLRDSTGDHIQQAKYRGRLKVSHKVPGDVSLQINTLQMDDRNHYTCE VTWQTPDGNQVIRDKIIELRVRKYNPPRINTEAPTTLHSSLEATTIMSSTSDLTTNG TGKLEETIAGSGRNLPIFAIIFIISLCCIVAVTIPYILFRCRTFQQEYVYGVSRVFA RKTSNSEETTRVTTIATDEPDSQALISDYSDDPCLSQEYQITIRSTMSIPAC(SEQ IDNO:80) HumanTim-3 >NM_032782.5HomosapienshepatitisAviruscellular (HAVCR2) receptor2(HAVCR2),mRNA ATTTGGAGAGTTAAAACTGTGCCTAACAGAGGTGTCCTCTGACTTTTCTTCTGCAAG CTCCATGTTTTCACATCTTCCCTTTGACTGTGTCCTGCTGCTGCTGCTGCTACTACT TACAAGGTCCTCAGAAGTGGAATACAGAGCGGAGGTCGGTCAGAATGCCTATCTGCC CTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGCAAAGG AGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGGGATGT GAATTATTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGAGATGTGTC CCTGACCATAGAGAATGTGACTCTAGCAGACAGTGGGATCTACTGCTGCCGGATCCA AATCCCAGGCATAATGAATGATGAAAAATTTAACCTGAAGTTGGTCATCAAACCAGC CAAGGTCACCCCTGCACCGACTCGGCAGAGAGACTTCACTGCAGCCTTTCCAAGGAT GCTTACCACCAGGGGACATGGCCCAGCAGAGACACAGACACTGGGGAGCCTCCCTGA TATAAATCTAACACAAATATCCACATTGGCCAATGAGTTACGGGACTCTAGATTGGC CAATGACTTACGGGACTCTGGAGCAACCATCAGAATAGGCATCTACATCGGAGCAGG GATCTGTGCTGGGCTGGCTCTGGCTCTTATCTTCGGCGCTTTAATTTTCAAATGGTA TTCTCATAGCAAAGAGAAGATACAGAATTTAAGCCTCATCTCTTTGGCCAACCTCCC TCCCTCAGGATTGGCAAATGCAGTAGCAGAGGGAATTCGCTCAGAAGAAAACATCTA TACCATTGAAGAGAACGTATATGAAGTGGAGGAGCCCAATGAGTATTATTGCTATGT CAGCAGCAGGCAGCAACCCTCACAACCTTTGGGTTGTCGCTTTGCAATGCCATAGAT CCAACCACCTTATTTTTGAGCTTGGTGTTTTGTCTTTTTCAGAAACTATGAGCTGTG TCACCTGACTGGTTTTGGAGGTTCTGTCCACTGCTATGGAGCAGAGTTTTCCCATTT TCAGAAGATAATGACTCACATGGGAATTGAACTGGGACCTGCACTGAACTTAAACAG GCATGTCATTGCCTCTGTATTTAAGCCAACAGAGTTACCCAACCCAGAGACTGTTAA TCATGGATGTTAGAGCTCAAACGGGCTTTTATATACACTAGGAATTCTTGACGTGGG GTCTCTGGAGCTCCAGGAAATTCGGGCACATCATATGTCCATGAAACTTCAGATAAA CTAGGGAAAACTGGGTGCTGAGGTGAAAGCATAACTTTTTTGGCACAGAAAGTCTAA AGGGGCCACTGATTTTCAAAGAGATCTGTGATCCCTTTTTGTTTTTTGTTTTTGAGA TGGAGTCTTGCTCTGTTGCCCAGGCTGGAGTGCAATGGCACAATCTCGGCTCACTGC AAGCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTGGCTGGG ATTACAGGCATGCACCACCATGCCCAGCTAATTTGTTGTATTTTTAGTAGAGACAGG GTTTCACCATGTTGGCCAGTGTGGTCTCAAACTCCTGACCTCATGATTTGCCTGCCT CGGCCTCCCAAAGCACTGGGATTACAGGCGTGAGCCACCACATCCAGCCAGTGATCC TTAAAAGATTAAGAGATGACTGGACCAGGTCTACCTTGATCTTGAAGATTCCCTTGG AATGTTGAGATTTAGGCTTATTTGAGCACTGCCTGCCCAACTGTCAGTGCCAGTGCA TAGCCCTTCTTTTGTCTCCCTTATGAAGACTGCCCTGCAGGGCTGAGATGTGGCAGG AGCTCCCAGGGAAAAACGAAGTGCATTTGATTGGTGTGTATTGGCCAAGTTTTGCTT GTTGTGTGCTTGAAAGAAAATATCTCTGACCAACTTCTGTATTCGTGGACCAAACTG AAGCTATATTTTTCACAGAAGAAGAAGCAGTGACGGGGACACAAATTCTGTTGCCTG GTGGAAAGAAGGCAAAGGCCTTCAGCAATCTATATTACCAGCGCTGGATCCTTTGAC AGAGAGTGGTCCCTAAACTTAAATTTCAAGACGGTATAGGCTTGATCTGTCTTGCTT ATTGTTGCCCCCTGCGCCTAGCACAATTCTGACACACAATTGGAACTTACTAAAAAT TTTTTTTTACTGTT(SEQIDNO:81) >NP_116171.3hepatitisAviruscellularreceptor2 precursor[Homosapiens] MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGA CPVFECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQI PGIMNDEKFNLKLVIKPAKVTPAPTRQRDFTAAFPRMLTTRGHGPAETQTLGSLPDI NLTQISTLANELRDSRLANDLRDSGATIRIGIYIGAGICAGLALALIFGALIFKWYS HSKEKIQNLSLISLANLPPSGLANAVAEGIRSEENIYTIEENVYEVEEPNEYYCYVS SRQQPSQPLGCRFAMP(SEQIDNO:82) MouseTim-3 >NM_134250.2MusmusculushepatitisAviruscellular (HAVCR2) receptor2(Havcr2),mRNA ACCATTTTAACCGAGGAGCTAAAGCTATCCCTACACAGAGCTGTCCTTGGATTTCCC CTGCCAAGTACTCATGTTTTCAGGTCTTACCCTCAACTGTGTCCTGCTGCTGCTGCA ACTACTACTTGCAAGGTCATTGGAAAATGCTTATGTGTTTGAGGTTGGTAAGAATGC CTATCTGCCCTGCAGTTACACTCTATCTACACCTGGGGCACTTGTGCCTATGTGCTG GGGCAAGGGATTCTGTCCTTGGTCACAGTGTACCAACGAGTTGCTCAGAACTGATGA AAGAAATGTGACATATCAGAAATCCAGCAGATACCAGCTAAAGGGCGATCTCAACAA AGGAGACGTGTCTCTGATCATAAAGAATGTGACTCTGGATGACCATGGGACCTACTG CTGCAGGATACAGTTCCCTGGTCTTATGAATGATAAAAAATTAGAACTGAAATTAGA CATCAAAGCAGCCAAGGTCACTCCAGCTCAGACTGCCCATGGGGACTCTACTACAGC TTCTCCAAGAACCCTAACCACGGAGAGAAATGGTTCAGAGACACAGACACTGGTGAC CCTCCATAATAACAATGGAACAAAAATTTCCACATGGGCTGATGAAATTAAGGACTC TGGAGAAACGATCAGAACTGCTATCCACATTGGAGTGGGAGTCTCTGCTGGGTTGAC CCTGGCACTTATCATTGGTGTCTTAATCCTTAAATGGTATTCCTGTAAGAAAAAGAA GTTATCGAGTTTGAGCCTTATTACACTGGCCAACTTGCCTCCAGGAGGGTTGGCAAA TGCAGGAGCAGTCAGGATTCGCTCTGAGGAAAATATCTACACCATCGAGGAGAACGT ATATGAAGTGGAGAATTCAAATGAGTACTACTGCTACGTCAACAGCCAGCAGCCATC CTGACCGCCTCTGGACTGCCACTTTTAAAGGCTCGCCTTCATTTCTGACTTTGGTAT TTCCCTTTTTGAAAACTATGTGATATGTCACTTGGCAACCTCATTGGAGGTTCTGAC CACAGCCACTGAGAAAAGAGTTCCAGTTTTCTGGGGATAATTAACTCACAAGGGGAT TCGACTGTAACTCATGCTACATTGAAATGCTCCATTTTATCCCTGAGTTTCAGGGAT CGGATCTCCCACTCCAGAGACTTCAATCATGCGTGTTGAAGCTCACTCGTGCTTTCA TACATTAGGAATGGTTAGTGTGATGTCTTTGAGACATAGAGGTTTGTGGTATATCTG CAAAGCTCCTGAACAGGTAGGGGGAATAAAGGGCTAAGATAGGAAGGTGAGGTTCTT TGTTGATGTTGAAAATCTAAAGAAGTTGGTAGCTTTTCTAGAGATTTCTGACCTTGA AAGATTAAGAAAAAGCCAGGTGGCATATGCTTAACACTATATAACTTGGGAACCTTA GGCAGGAGGGTGATAAGTTCAAGGTCAGCCAGGGCTATGCTGGTAAGACTGTCTCAA AATCCAAAGACGAAAATAAACATAGAGACAGCAGGAGGCTGGAGATGAGGCTCGGAC AGTGAGGTGCATTTTGTACAAGCACGAGGAATCTATATTTGATCGTAGACCCCACAT GAAAAAGCTAGGCCTGGTAGAGCATGCTTGTAGACTCAAGAGATGGAGAGGTAAAGG CACAACAGATCCCCGGGGCTTGCGTGCAGTCAGCTTAGCCTAGGTGCTGAGTTCCAA GTCCACAAGAGTCCCTGTCTCAAAGTAAGATGGACTGAGTATCTGGCGAATGTCCAT GGGGGTTGTCCTCTGCTCTCAGAAGAGACATGCACATGAACCTGCACACACACACAC ACACACACACACACACACACACACACACACACACACACACACATGAAATGAAGGTTC TCTCTGTGCCTGCTACCTCTCTATAACATGTATCTCTACAGGACTCTCCTCTGCCTC TGTTAAGACATGAGTGGGAGCATGGCAGAGCAGTCCAGTAATTAATTCCAGCACTCA GAAGGCTGGAGCAGAAGCGTGGAGAGTTCAGGAGCACTGTGCCCAACACTGCCAGAC TCTTCTTACAGAAGAAAAAGGTTACCCGCAAGCAGCCTGCTGTCTGTAAAAGGAAAC CCTGCGAAAGGCAAACTTTGACTGTTGTGTGCTCAAGGGGAACTGACTCAGACAACT TCTCCATTCCTGGAGGAAACTGGAGCTGTTTCTGACAGAAGAACAACCGGTGACTGG GACATACGAAGGCAGAGCTCTTGCAGCAATCTATATAGTCAGCAAAATATTCTTTGG GAGGACAGTCGTCACCAAATTGATTTCCAAGCCGGTGGACCTCAGTTTCATCTGGCT TACAGCTGCCTGCCCAGTGCCCTTGATCTGTGCTGGCTCCCATCTATAACAGAATCA AATTAAATAGACCCCGAGTGAAAATATTAAGTGAGCAGAAAGGTAGCTTTGTTCAAA GATTTTTTTGCATTGGGGAGCAACTGTGTACATCAGAGGACATCTGTTAGTGAGGAC ACCAAAACCTGTGGTACCGTTTTTTCATGTATGAATTTTGTTGTTTAGGTTGCTTCT AGCTAGCTGTGGAGGTCCTGGCTTTCTTAGGTGGGTATGGAAGGGAGACCATCTAAC AAAATCCATTAGAGATAACAGCTCTCATGCAGAAGGGAAAACTAATCTCAAATGTTT TAAAGTAATAAAACTGTACTGGCAAAGTACTTTGAGCATATTTAAA(SEQID NO:83) >NP_599011.2hepatitisAviruscellularreceptor2 homologprecursor[Musmusculus] MFSGLTLNCVLLLLQLLLARSLENAYVFEVGKNAYLPCSYTLSTPGALVPMCWGKGF CPWSQCTNELLRTDERNVTYQKSSRYQLKGDLNKGDVSLIIKNVTLDDHGTYCCRIQ FPGLMNDKKLELKLDIKAAKVTPAQTAHGDSTTASPRTLTTERNGSETQTLVTLHNN NGTKISTWADEIKDSGETIRTAIHIGVGVSAGLTLALIIGVLILKWYSCKKKKLSSL SLITLANLPPGGLANAGAVRIRSEENIYTIEENVYEVENSNEYYCYVNSQQPS (SEQIDNO:84) HumanTim-4 >NM_138379.3HomosapiensTcellimmunoglobulinandmucin (TIMD4) domaincontaining4(TIMD4),transcriptvariant1,mRNA AGACTCCTGGGTCCGGTCAACCGTCAAAATGTCCAAAGAACCTCTCATTCTCTGGCT GATGATTGAGTTTTGGTGGCTTTACCTGACACCAGTCACTTCAGAGACTGTTGTGAC GGAGGTTTTGGGTCACCGGGTGACTTTGCCCTGTCTGTACTCATCCTGGTCTCACAA CAGCAACAGCATGTGCTGGGGGAAAGACCAGTGCCCCTACTCCGGTTGCAAGGAGGC GCTCATCCGCACTGATGGAATGAGGGTGACCTCAAGAAAGTCAGCAAAATATAGACT TCAGGGGACTATCCCGAGAGGTGATGTCTCCTTGACCATCTTAAACCCCAGTGAAAG TGACAGCGGTGTGTACTGCTGCCGCATAGAAGTGCCTGGCTGGTTCAACGATGTAAA GATAAACGTGCGCCTGAATCTACAGAGAGCCTCAACAACCACGCACAGAACAGCAAC CACCACCACACGCAGAACAACAACAACAAGCCCCACCACCACCCGACAAATGACAAC AACCCCAGCTGCACTTCCAACAACAGTCGTGACCACACCCGATCTCACAACCGGAAC ACCACTCCAGATGACAACCATTGCCGTCTTCACAACAGCAAACACGTGCCTTTCACT AACCCCAAGCACCCTTCCGGAGGAAGCCACAGGTCTTCTGACTCCCGAGCCTTCTAA GGAAGGGCCCATCCTCACTGCAGAATCAGAAACTGTCCTCCCCAGTGATTCCTGGAG TAGTGTTGAGTCTACTTCTGCTGACACTGTCCTGCTGACATCCAAAGAGTCCAAAGT TTGGGATCTCCCATCAACATCCCACGTGTCAATGTGGAAAACGAGTGATTCTGTGTC TTCTCCTCAGCCTGGAGCATCTGATACAGCAGTTCCTGAGCAGAACAAAACAACAAA AACAGGACAGATGGATGGAATACCCATGTCAATGAAGAATGAAATGCCCATCTCCCA ACTACTGATGATCATCGCCCCCTCCTTGGGATTTGTGCTCTTCGCATTGTTTGTGGC GTTTCTCCTGAGAGGGAAACTCATGGAAACCTATTGTTCGCAGAAACACACAAGGCT AGACTACATTGGAGATAGTAAAAATGTCCTCAATGACGTGCAGCATGGAAGGGAAGA CGAAGACGGCCTTTTTACCCTCTAACAACGCAGTAGCATGTTAGATTGAGGATGGGG GCATGACACTCCAGTGTCAAAATAAGTCTTAGTAGATTTCCTTGTTTCATAAAAAAG ACTCACTTATTCCATGGATGTCATTGATCCAGGCTTGCTTTAGTTTCATGAATGAAG GGTACTTTAGAGACCACAA(SEQIDNO:85) >NP_612388.2T-cellimmunoglobulinandmucindomain- containingprotein4isoform1precursor[Homosapiens] MSKEPLILWLMIEFWWLYLTPVTSETVVTEVLGHRVTLPCLYSSWSHNSNSMCWGKD QCPYSGCKEALIRTDGMRVTSRKSAKYRLQGTIPRGDVSLTILNPSESDSGVYCCRI EVPGWFNDVKINVRLNLQRASTTTHRTATTTTRRTTTTSPTTTRQMTTTPAALPTTV VTTPDLTTGTPLQMTTIAVFTTANTCLSLTPSTLPEEATGLLTPEPSKEGPILTAES ETVLPSDSWSSVESTSADTVLLTSKESKVWDLPSTSHVSMWKTSDSVSSPQPGASDT AVPEQNKTTKTGQMDGIPMSMKNEMPISQLLMIIAPSLGFVLFALFVAFLLRGKLME TYCSQKHTRLDYIGDSKNVLNDVQHGREDEDGLFTL(SEQIDNO:86) MouseTim-4 >NM_178759.4MusmusculusTcellimmunoglobulinandmucin (TIMD4) domaincontaining4(Timd4),mRNA AGATCCTATCAAAATGTCCAAGGGGCTTCTCCTCCTCTGGCTGGTGACGGAGCTCTG GTGGCTTTATCTGACACCAGCTGCCTCAGAGGATACAATAATAGGGTTTTTGGGCCA GCCGGTGACTTTGCCTTGTCATTACCTCTCGTGGTCCCAGAGCCGCAACAGTATGTG CTGGGGCAAAGGTTCATGTCCCAATTCCAAGTGCAATGCAGAGCTTCTCCGTACAGA TGGAACAAGAATCATCTCCAGGAAGTCAACAAAATATACACTTTTGGGGAAGGTCCA GTTTGGTGAAGTGTCCTTGACCATCTCAAACACCAATCGAGGTGACAGTGGGGTGTA CTGCTGCCGTATAGAGGTGCCTGGCTGGTTCAATGATGTCAAGAAGAATGTGCGCTT GGAGCTGAGGAGAGCCACAACAACCAAAAAACCAACAACAACCACCCGGCCAACCAC CACCCCTTATGTGACCACCACCACCCCAGAGCTGCTTCCAACAACAGTCATGACCAC ATCTGTTCTCCCAACCACCACACCACCCCAGACACTAGCCACCACTGCCTTCAGTAC AGCAGTGACCACGTGCCCCTCAACAACACCTGGCTCCTTCTCACAAGAAACCACAAA AGGGTCCGCCTTCACTACAGAATCAGAAACTCTGCCTGCATCCAATCACTCTCAAAG AAGCATGATGACCATATCTACAGACATAGCCGTACTCAGGCCCACAGGCTCTAACCC TGGGATTCTCCCATCCACTTCACAGCTGACGACACAGAAAACAACATTAACAACAAG TGAGTCTTTGCAGAAGACAACTAAATCACATCAGATCAACAGCAGACAGACCATCTT GATCATTGCCTGCTGTGTGGGATTTGTGCTAATGGTGTTATTGTTTCTGGCGTTTCT CCTTCGAGGGAAAGTCACAGGAGCCAACTGTTTGCAGAGACACAAGAGGCCAGACAA CACTGAAGATAGTGACAGCGTCCTCAATGACATGTCACACGGGAGGGATGATGAAGA CGGGATCTTCACTCTCTGACTCACCATCTTTATTTAGGATTAAGGATAGGGAATGGC ACTTGAATTGTCAAAATAAGTTTGGGGACATTGTAATTTCCGTTTAAAGTCTCACTC TGTTTACTGATGCTGTGGGTCCTGTCTGGTTGTATCTTCCCACATGAAGGTGCTTTA GAGACACATTTTCCCTGCCTCGTGCCTTAGTCCTCTTTGTTGTTTTGTGGCTAGGTG ACTTTTCACACTGGGCTTGAACACTGTCAGTGATGGTGAAATCCTTGCCACAGCTTT GGGAGTCTCTTGCAGTCTCCCAGCAGTAGAGGGAGTTAGAAATATCCAGAGGGGAAA AAAAAATCTCTCTTTTCAGACAGTATCTGCTTTATTGGTGGTAGCTGAACTTCATTT ATACAGAGCTCCTTTAACCTGTCTGTCTTCTTCTTGGTATCTAAGCTGCCTTTTGTT TTTGTTTTTGTTTTTGTTTTTATGATATTAACTTCTTTTCACATTCAAGTTTCTTTA AAGTTGACTATAGTGCCTTCTGAACTCTTGCAGAGAGTTTGGATTTTGGAAGCTGCC AGGTACCCATCACAGCAGGGGTGCCAGTGACAAGGATGGTGTACAAATGAAACACTG AAGCTATCCAAATAAATTCCTCTAAGTGTAATTCATTTTACTGCAGCACAGGAAGAA CAAATTTGTCTTACAACTTTAATAATTAGTACCATTATGAACCCTAGGAGAGAAATA AGAGCAAATACCTGTTGAATAAATGAATGTAAGAAAATGTGTGTCTGAGCAAGAATA CTCTGTCTGGCTACTATGGGAAGCTAGCTAGATCTGAAAGACATTCTCAGACTATCC TCATGTTCAAGGCATTAAAGGAATAAGCCTCCAGCCCCTAACCTTAGGAGAATTCTG CAGTCAAGTGAGGAGTTTTTAAAACAGGAATCTCTAGGTTCCAGTCCTCTAGCTATT CTTTTATGCTTAGTCCAGGTAATGAGTTGAACATCCAAGTATTTTTTAAGGACCCAA AGAAATGCAACCAGAGCTATTACCAGAATTTTGGAGTGGTCCTCCTAGAGTTGCCGC ATGTTGCTGGGAAAATTGGGGTCTTAGAGTTCTTAGTCTACTTAATAAAAGAATTTT AAAAAATGG(SEQIDNO:87) >NP_848874.3T-cellimmunoglobulinandmucindomain- containingprotein4precursor[Musmusculus] MSKGLLLLWLVTELWWLYLTPAASEDTIIGFLGQPVTLPCHYLSWSQSRNSMCWGKG SCPNSKCNAELLRTDGTRIISRKSTKYTLLGKVQFGEVSLTISNTNRGDSGVYCCRI EVPGWFNDVKKNVRLELRRATTTKKPTTTTRPTTTPYVTTTTPELLPTTVMTTSVLP TTTPPQTLATTAFSTAVTTCPSTTPGSFSQETTKGSAFTTESETLPASNHSQRSMMT ISTDIAVLRPTGSNPGILPSTSQLTTQKTTLTTSESLQKTTKSHQINSRQTILIIAC CVGFVLMVLLFLAFLLRGKVTGANCLQRHKRPDNTEDSDSVLNDMSHGRDDEDGIFT L(SEQIDNO:88) Human >NM_001712.5HomosapiensCEAcelladhesionmolecule1 CEACAM1 (CEACAM1),transcriptvariant1,mRNA AGCACAGAGAGTGGAAAACAGCAGAGGTGACAGAGCAGCCGTGCTCGAAGCGTTCCT GGAGCCCAAGCTCTCCTCCACAGGTGAAGACAGGGCCAGCAGGAGACACCATGGGGC ACCTCTCAGCCCCACTTCACAGAGTGCGTGTACCCTGGCAGGGGCTTCTGCTCACAG CCTCACTTCTAACCTTCTGGAACCCGCCCACCACTGCCCAGCTCACTACTGAATCCA TGCCATTCAATGTTGCAGAGGGGAAGGAGGTTCTTCTCCTTGTCCACAATCTGCCCC AGCAACTTTTTGGCTACAGCTGGTACAAAGGGGAAAGAGTGGATGGCAACCGTCAAA TTGTAGGATATGCAATAGGAACTCAACAAGCTACCCCAGGGCCCGCAAACAGCGGTC GAGAGACAATATACCCCAATGCATCCCTGCTGATCCAGAACGTCACCCAGAATGACA CAGGATTCTACACCCTACAAGTCATAAAGTCAGATCTTGTGAATGAAGAAGCAACTG GACAGTTCCATGTATACCCGGAGCTGCCCAAGCCCTCCATCTCCAGCAACAACTCCA ACCCTGTGGAGGACAAGGATGCTGTGGCCTTCACCTGTGAACCTGAGACTCAGGACA CAACCTACCTGTGGTGGATAAACAATCAGAGCCTCCCGGTCAGTCCCAGGCTGCAGC TGTCCAATGGCAACAGGACCCTCACTCTACTCAGTGTCACAAGGAATGACACAGGAC CCTATGAGTGTGAAATACAGAACCCAGTGAGTGCGAACCGCAGTGACCCAGTCACCT TGAATGTCACCTATGGCCCGGACACCCCCACCATTTCCCCTTCAGACACCTATTACC GTCCAGGGGCAAACCTCAGCCTCTCCTGCTATGCAGCCTCTAACCCACCTGCACAGT ACTCCTGGCTTATCAATGGAACATTCCAGCAAAGCACACAAGAGCTCTTTATCCCTA ACATCACTGTGAATAATAGTGGATCCTATACCTGCCACGCCAATAACTCAGTCACTG GCTGCAACAGGACCACAGTCAAGACGATCATAGTCACTGAGCTAAGTCCAGTAGTAG CAAAGCCCCAAATCAAAGCCAGCAAGACCACAGTCACAGGAGATAAGGACTCTGTGA ACCTGACCTGCTCCACAAATGACACTGGAATCTCCATCCGTTGGTTCTTCAAAAACC AGAGTCTCCCGTCCTCGGAGAGGATGAAGCTGTCCCAGGGCAACACCACCCTCAGCA TAAACCCTGTCAAGAGGGAGGATGCTGGGACGTATTGGTGTGAGGTCTTCAACCCAA TCAGTAAGAACCAAAGCGACCCCATCATGCTGAACGTAAACTATAATGCTCTACCAC AAGAAAATGGCCTCTCACCTGGGGCCATTGCTGGCATTGTGATTGGAGTAGTGGCCC TGGTTGCTCTGATAGCAGTAGCCCTGGCATGTTTTCTGCATTTCGGGAAGACCGGCA GGGCAAGCGACCAGCGTGATCTCACAGAGCACAAACCCTCAGTCTCCAACCACACTC AGGACCACTCCAATGACCCACCTAACAAGATGAATGAAGTTACTTATTCTACCCTGA ACTTTGAAGCCCAGCAACCCACACAACCAACTTCAGCCTCCCCATCCCTAACAGCCA CAGAAATAATTTATTCAGAAGTAAAAAAGCAGTAATGAAACCTGTCCTGCTCACTGC AGTGCTGATGTATTTCAAGTCTCTCACCCTCATCACTAGGAGATTCCTTTCCCCTGT AGGGGTAGAGGGGTGGGGACAGAAACAACTTTCTCCTACTCTTCCTTCCTAATAGGC ATCTCCAGGCTGCCTGGTCACTGCCCCTCTCTCAGTGTCAATAGATGAAAGTACATT GGGAGTCTGTAGGAAACCCAACCTTCTTGTCATTGAAATTTGGCAAAGCTGACTTTG GGAAAGAGGGACCAGAACTTCCCCTCCCTTCCCCTTTTCCCAACCTGGACTTGTTTT AAACTTGCCTGTTCAGAGCACTCATTCCTTCCCACCCCCAGTCCTGTCCTATCACTC TAATTCGGATTTGCCATAGCCTTGAGGTTATGTCCTTTTCCATTAAGTACATGTGCC AGGAAACAAGAGAGAGAGAAAGTAAAGGCAGTAATGCCTTCTCCTATTTCTCCAAAG CCTTGTGTGAACTCACCAAACACAAGAAAATCAAATATATAACCAATAGTGAAATGC CACACCTTTGTCCACTGTCAGGGTTGTCTACCTGTAGGATCAGGGTCTAAGCACCTT GGTGCTTAGCTAGAATACCACCTAATCCTTCTGGCAAGCCTGTCTTCAGAGAACCCA CTAGAAGCAACTAGGAAAATCACTTGCCAAAATCCAAGGCAATTCCTGATGGAAAAT GCAAAAGCACATATATGTTTTAATATCTTTATGGGCTCTGTTCAAGGCAGTGCTGAG AGGGAGGGGTTATAGCTTCAGGAGGGAACCAGCTTCTGATAAACACAATCTGCTAGG AACTTGGGAAAGGAATCAGAGAGCTGCCCTTCAGCGATTATTTAAATTATTGTTAAA GAATACACAATTTGGGGTATTGGGATTTTTCTCCTTTTCTCTGAGACATTCCACCAT TTTAATTTTTGTAACTGCTTATTTATGTGAAAAGGGTTATTTTTACTTAGCTTAGCT ATGTCAGCCAATCCGATTGCCTTAGGTGAAAGAAACCACCGAAATCCCTCAGGTCCC TTGGTCAGGAGCCTCTCAAGATTTTTTTTGTCAGAGGCTCCAAATAGAAAATAAGAA AAGGTTTTCTTCATTCATGGCTAGAGCTAGATTTAACTCAGTTTCTAGGCACCTCAG ACCAATCATCAACTACCATTCTATTCCATGTTTGCACCTGTGCATTTTCTGTTTGCC CCCATTCACTTTGTCAGGAAACCTTGGCCTCTGCTAAGGTGTATTTGGTCCTTGAGA AGTGGGAGCACCCTACAGGGACACTATCACTCATGCTGGTGGCATTGTTTACAGCTA GAAAGCTGCACTGGTGCTAATGCCCCTTGGGGAAATGGGGCTGTGAGGAGGAGGATT ATAACTTAGGCCTAGCCTCTTTTAACAGCCTCTGAAATTTATCTTTTCTTCTATGGG GTCTATAAATGTATCTTATAATAAAAAGGAAGGACAGGAGGAAGACAGGCAAATGTA CTTCTCACCCAGTCTTCTACACAGATGGAATCTCTTTGGGGCTAAGAGAAAGGTTTT ATTCTATATTGCTTACCTGATCTCATGTTAGGCCTAAGAGGCTTTCTCCAGGAGGAT TAGCTTGGAGTTCTCTATACTCAGGTACCTCTTTCAGGGTTTTCTAACCCTGACACG GACTGTGCATACTTTCCCTCATCCATGCTGTGCTGTGTTATTTAATTTTTCCTGGCT AAGATCATGTCTGAATTATGTATGAAAATTATTCTATGTTTTTATAATAAAAATAAT ATATCAGACATCGA(SEQIDNO:89) >NP_001703.2carcinoembryonicantigen-relatedcell adhesionmolecule1isoform1precursor[Homosapiens] MGHLSAPLHRVRVPWQGLLLTASLLTFWNPPTTAQLTTESMPFNVAEGKEVLLLVHN LPQQLFGYSWYKGERVDGNRQIVGYAIGTQQATPGPANSGRETIYPNASLLIQNVTQ NDTGFYTLQVIKSDLVNEEATGQFHVYPELPKPSISSNNSNPVEDKDAVAFTCEPET QDTTYLWWINNQSLPVSPRLQLSNGNRTLTLLSVTRNDTGPYECEIQNPVSANRSDP VTLNVTYGPDTPTISPSDTYYRPGANLSLSCYAASNPPAQYSWLINGTFQQSTQELF IPNITVNNSGSYTCHANNSVTGCNRTTVKTIIVTELSPVVAKPQIKASKTTVTGDKD SVNLTCSTNDTGISIRWFFKNQSLPSSERMKLSQGNTTLSINPVKREDAGTYWCEVF NPISKNQSDPIMLNVNYNALPQENGLSPGAIAGIVIGVVALVALIAVALACFLHFGK TGRASDQRDLTEHKPSVSNHTQDHSNDPPNKMNEVTYSTLNFEAQQPTQPTSASPSL TATEIIYSEVKKQ(SEQIDNO:90) Mouse >NM_01039185.1Musmusculuscarcinoembryonicantigen- CEACAM1 relatedcelladhesionmolecule1(Ceacam1),transcript variant1,mRNA AAAGCTCCTTTAAGAAAAGCAGGGCAGATATCAGGGCAGCCTGGCTTAGCAGTAGTG TTGGAGAAGAAGCTAGCAGGCAGGCAGCAGAGACATGGAGCTGGCCTCAGCACATCT CCACAAAGGGCAGGTTCCCTGGGGAGGACTACTGCTCACAGCCTCACTTTTAGCCTC CTGGAGCCCTGCCACCACTGCTGAAGTCACCATTGAGGCTGTGCCGCCCCAGGTTGC TGAAGACAACAATGTTCTTCTACTTGTTCACAATCTGCCCCTGGCGCTTGGAGCCTT TGCCTGGTACAAGGGAAACACTACGGCTATAGACAAAGAAATTGCACGATTTGTACC AAATAGTAATATGAATTTCACGGGGCAAGCATACAGCGGCAGAGAGATAATATACAG CAATGGATCCCTGCTCTTCCAAATGATCACCATGAAGGATATGGGAGTCTACACACT AGATATGACAGATGAAAACTATCGTCGTACTCAGGCGACTGTGCGATTTCATGTACA CCCCATATTATTAAAGCCCAACATCACAAGCAACAACTCCAATCCCGTGGAGGGTGA CGACTCCGTATCATTAACCTGTGACTCTTACACTGACCCTGATAATATAAACTACCT GTGGAGCAGAAATGGTGAAAGCCTTTCAGAAGGTGACAGGCTGAAGCTGTCTGAGGG CAACAGGACTCTCACTTTACTCAATGTCACGAGGAATGACACAGGACCCTATGTGTG TGAAACCCGGAATCCAGTGAGTGTCAACCGAAGTGACCCATTCAGCCTGAACATTAT CTATGGTCCGGACACCCCGATTATATCCCCCTCAGATATTTATTTGCATCCAGGGTC AAACCTCAACCTCTCCTGCCATGCAGCCTCTAACCCACCTGCACAGTACTTTTGGCT TATCAATGAGAAGCCCCATGCATCCTCCCAAGAGCTCTTTATCCCCAACATCACTAC TAATAATAGCGGAACCTATACCTGCTTCGTCAATAACTCTGTCACTGGCCTCAGTAG GACCACAGTCAAGAACATTACAGTCCTTGAGCCAGTGACTCAGCCCTTCCTCCAAGT CACCAACACCACAGTCAAAGAACTAGACTCTGTGACCCTGACCTGCTTGTCGAATGA CATTGGAGCCAACATCCAGTGGCTCTTCAATAGCCAGAGTCTTCAGCTCACAGAGAG AATGACACTCTCCCAGAACAACAGCATCCTCAGAATAGACCCTATTAAGAGGGAAGA TGCCGGCGAGTATCAGTGTGAAATCTCGAATCCAGTCAGCGTCAGGAGGAGCAACTC AATCAAGCTGGACATAATATTTGACCCAACACAAGGAGGCCTCTCAGATGGCGCCAT TGCTGGCATCGTGATTGGAGTTGTGGCTGGGGTGGCTCTAATAGCAGGGCTGGCATA TTTCCTCTATTCCAGGAAGTCTGGCGGGGGAAGTGACCAGCGAGATCTCACAGAGCA CAAACCCTCAGCCTCCAACCACAATCTGGCTCCTTCTGACAACTCTCCTAACAAGGT GGATGACGTCGCATACACTGTCCTGAACTTCAATTCCCAGCAACCCAACCGGCCAAC TTCAGCCCCTTCTTCTCCAAGAGCCACAGAAACAGTTTATTCAGAAGTAAAAAAGAA GTGAGCATAATCTGTCCGTCTGTCCTGCTGGCTGCACCAGTGATGCATTCCCGGATT CTGTTCCTCACTGGAGGGTCTCAGCACACACACACACGTACACATGCGCGCGCGCAC ACACACACACACACACACACACACACACTTACACACACACTCATGCATTCACTCTAT TGACTCCTTCAGTGTCTATAGAAGAAAAGGTGGATCCTGGAGCCTACAGAAAACTCA ACCCTTCTAGGCTTTCAAATTTGGCTGAGAGTGAGGTATCAAAATTTCTCACCCTTT CACTTTCCTGACCCAGATTGTTGAAAATTGACCTATTCAGAGCACCTTCATTCCCCT CCCAACTCCAAGTCCTGCCCTATCAGAGTCTGACTTGAATTTCCATAAACCTTGGAG GTCACCTAAGTGCTTACGCCAAACAAAACAAAACAAAACAAAACAAAACAAAACAAA ACAAAACAAAACAAACCAGAAGCAGGAAATGGCCAGTCCCATATCTTTAAAGGCTGA TTGGAAGCCACCATACATGAGAAGATCAAACCTCCATGGGCAATCTACACACCCGAC AACTGTCATGCTTACCCATCTGGGACATTCGAGTCTCTGAACCTTGTGCCCTCACGC CTGAGCCCTTCTCTGAGCCTTTCTCCAGAAAATCCACTCACAGCAACTAGAGAGGCT CTTTGTCAGCAACTCCAAGCAAACTGCTAGGCAGGATTCAGAAGAAAAGACAGCATC TCTAACATCCACCAGGAAGGTGCCCAGAAAAGCAGAGCTGGTGACTTTGGACTGACA GACATCTGGAGTGTGAAAAAGCAGCACAGAGCTAACCTTCGGAGAGTGTTGAAATTA TTTGAAAAGAAGCCATATTTGGAGGTATTGGAGTTTTCCTCTTTCTGAGACAATCCA CTATTTGAAAATTGTAGCTACTGAATTGCCTCTCAGTATGCGAGCTGATCACTTTGC CTTAGGGCCACTAGATTTCTGTCTCCCTTAGCCCCTCAAGCCCTTTTGATCATGAGT TCCAAACCAAAAATAAATAAATGAACAGTGAGGCAGTCCCTTGCAGTACCACTGTCA TGGGTCAGGCTAAGCCTCCTGCTTTTCTGAATTAGTCAAGAAAAGCCTTGGTTTCCC TTTTTCCATCTCTTTATCTTGTCTTTCAGATACTGGCCAGAGCCTGGACACTCTTCC TCTGAGATCTCCAGCTTCTCTGCCTTCTTGTGTTTCTTTTAAACTCTAACAAAAACT GTTCTCACCTTCAAAAAATAAAATAATAACAAGCTTTCCACATCCCCACCAAAGAGG GACCCAGCTAGGTTTCTGGAAACCCAGCACCAGCCTCCAGCTGCCCTTCTGCAGTGT TTCTGCCTCTGTTTCCCTTTCGTTTTGACTTTTTTCCTTCTTTTGAGACAGAGTTCC AGCATGGAGCCTGTGCAGGTTTCAATCCCACAGTAACACCTTCTGCAGCACCCCACC TGCTCAGACTGCAGCCCTGGCCACCAGGCCTGGCTACCTGGACATTCTGTCTGCCCT GCACTCTCAGGAAACCTTGGCCTCTGCTACTGTCTGTTTGGCTCATTCAAAGTGTGT CCTTAAAGGAATGCAGTCACCCATGCCAGAGGCAGTGTTTACAGCCTGGAATGCTCT GCACTTCCAGTGGACCAGTGCTCCACCGGAAGTGGGCTGTTAGCAGGGTCCTCTCAC CTGGCCCTGGCCTTTCTGTAGCCTTGAATCCTGCCTTCCCCACCAGGGCACCAGGGA TGAGTGCAGCAGCAGGAGGAGAGGCAAACAGTCACCTCAGGAACCTTCTGAGCTAAG GCACACCCTCTGTGCCTGTCAAGCAAAGGTTGTATTGGATATCAAGTGTTTGGTCTC ACGCCAAGCCAACAGGCTTTGGAGAGAATTAATTAGTTCTCCTACTCAGGGATTTCT TTCAGTCCTAACACAGCCTGTGTATATTTTGCTTCACCCACGCAATGCTGGATTATT TAATTTTGCCCGGCTTAAGACAAATCTGAGTTACTTGTAAATTTGCTCTATGTTCAT AATAAAAATGTATTATATATCACTGATAGCA(SEQIDNO:91) >NP_001034274.1carcinoembryonicantigen-relatedcell adhesionmolecule1isoform1precursor[Musmusculus] MELASAHLHKGQVPWGGLLLTASLLASWSPATTAEVTIEAVPPQVAEDNNVLLLVHN LPLALGAFAWYKGNTTAIDKEIARFVPNSNMNFTGQAYSGREIIYSNGSLLFQMITM KDMGVYTLDMTDENYRRTQATVRFHVHPILLKPNITSNNSNPVEGDDSVSLTCDSYT DPDNINYLWSRNGESLSEGDRLKLSEGNRTLTLLNVTRNDTGPYVCETRNPVSVNRS DPFSLNIIYGPDTPIISPSDIYLHPGSNLNLSCHAASNPPAQYFWLINEKPHASSQE LFIPNITTNNSGTYTCFVNNSVTGLSRTTVKNITVLEPVTQPFLQVTNTTVKELDSV TLTCLSNDIGANIQWLFNSQSLQLTERMTLSQNNSILRIDPIKREDAGEYQCEISNP VSVRRSNSIKLDIIFDPTQGGLSDGAIAGIVIGVVAGVALIAGLAYFLYSRKSGGGS DQRDLTEHKPSASNHNLAPSDNSPNKVDDVAYTVLNFNSQQPNRPTSAPSSPRATET VYSEVKKK(SEQIDNO:92) Human >NM_007048.6Homosapiensbutyrophilinsubfamily3member BTN3A1 A1(BTN3A1),transcriptvariant1,mRNA ATTCCTCACGATGACCCGACAGTCTCTGCTTTCTTTTTCCTTTCTTCCAGAAGGAGA TTTAACCATAGTAGAAAGAATGGAGAACTATTAACTGCCTTTCTTCTGTGGGCTGTG ATTTTCAGAGGGGAATGCTAAGAGGTGATTTTCAATGTTGGGACTCAAAGGTGAAGA CACTGAAGGACAGAATTTTTGGCAGAGGAAAGATCTTCTTCGGTCACCATACTTGAG TTAGCTCTAGGGAAGTGGAGGTTTCCATTTGGAATTCTATAGCTTCTTCCAGGTCAT AGTGTCTGCCCCCCACCTTCCAGTATCTCCTGATATGCAGCATGAATGAAAATGGCA AGTTTCCTGGCCTTCCTTCTGCTCAACTTTCGTGTCTGCCTCCTTTTGCTTCAGCTG CTCATGCCTCACTCAGCTCAGTTTTCTGTGCTTGGACCCTCTGGGCCCATCCTGGCC ATGGTGGGTGAAGACGCTGATCTGCCCTGTCACCTGTTCCCGACCATGAGTGCAGAG ACCATGGAGCTGAAGTGGGTGAGTTCCAGCCTAAGGCAGGTGGTGAACGTGTATGCA GATGGAAAGGAAGTGGAAGACAGGCAGAGTGCACCGTATCGAGGGAGAACTTCGATT CTGCGGGATGGCATCACTGCAGGGAAGGCTGCTCTCCGAATACACAACGTCACAGCC TCTGACAGTGGAAAGTACTTGTGTTATTTCCAAGATGGTGACTTCTATGAAAAAGCC CTGGTGGAGCTGAAGGTTGCAGCACTGGGTTCTGATCTTCACGTTGATGTGAAGGGT TACAAGGATGGAGGGATCCATCTGGAGTGCAGGTCCACTGGCTGGTACCCCCAACCC CAAATACAGTGGAGCAACAACAAGGGAGAGAACATCCCGACTGTGGAAGCACCTGTG GTTGCAGACGGAGTGGGCCTGTATGCAGTAGCAGCATCTGTGATCATGAGAGGCAGC TCTGGGGAGGGTGTATCCTGTACCATCAGAAGTTCCCTCCTCGGCCTGGAAAAGACA GCCAGCATTTCCATCGCAGACCCCTTCTTCAGGAGCGCCCAGAGGTGGATCGCCGCC CTGGCAGGGACCCTGCCTGTCTTGCTGCTGCTTCTTGGGGGAGCCGGTTACTTCCTG TGGCAACAGCAGGAGGAAAAAAAGACTCAGTTCAGAAAGAAAAAGAGAGAGCAAGAG TTGAGAGAAATGGCATGGAGCACAATGAAGCAAGAACAAAGCACAAGAGTGAAGCTC CTGGAGGAACTCAGATGGAGAAGTATCCAGTATGCATCTCGGGGAGAGAGACATTCA GCCTATAATGAATGGAAAAAGGCCCTCTTCAAGCCTGCGGATGTGATTCTGGATCCA AAAACAGCAAACCCCATCCTCCTTGTTTCTGAGGACCAGAGGAGTGTGCAGCGTGCC AAGGAGCCCCAGGATCTGCCAGACAACCCTGAGAGATTTAATTGGCATTATTGTGTT CTCGGCTGTGAGAGCTTCATATCAGGGAGACATTACTGGGAGGTGGAGGTAGGGGAC AGGAAAGAGTGGCATATAGGGGTGTGCAGTAAGAATGTGCAGAGAAAAGGCTGGGTC AAAATGACACCTGAGAATGGATTCTGGACTATGGGGCTGACTGATGGGAATAAGTAT CGGACTCTAACTGAGCCCAGAACCAACCTGAAACTTCCTAAGCCCCCTAAGAAAGTG GGGGTCTTCCTGGACTATGAGACTGGAGATATCTCATTCTACAATGCTGTGGATGGA TCGCATATTCATACTTTCCTGGACGTCTCCTTCTCTGAGGCTCTATATCCTGTTTTC AGAATTTTGACCTTGGAGCCCACGGCCCTGACTATTTGTCCAGCGTGAAAAGAAGAA GAGAGTTCCTCCAATTCTGACCGAGTGCTGATCATTCCCTAGAGACACCAGTAACCC CGGGCTTAGCTAACGAAAGTGGGGAGCCTCAGGCTGAAGTAACTTTTCTCTGCTTCT CCCTGCCCAGCTCAGAGCTGAGGGCCTCCCCCTCCACAGCAACCAATCACAACCATA AAGCTACAAGCACGCACTGAAGCACTTTACTGATACTCATTCAATTATTCATATGAC AGTTGTTTGAGTTTGGTACCATCTTATTTTCCCCTTATACAGATAAGGAAACTGGGG TGCAGAAAAGTGAATTGACTACAAAGTAGACATGACTAGTTAACAACACAGCTGGGA TCTAAACAGCAATAACTAACATTAATGGAGAACTTAAAATGCTCTGAGTGCTGTGTT ATGAGCTTTGGTGGATGTCACTCCTTTAATCCTCGCAACACCCTGTCGGGTAGTCTC ATTTAGCAAGTATGGAAGTTGAGGCAGGGCAACATTAAGCAACTTACATAACTCATG CAGTAATTTCTGCAGTTGGGAGATGTTCAGCTTCAGTCCCCGGCCCTATGGCCGTTC TTTTCCACCCTGTTTCTTCCCCCATAGGAAGAACCCACCTGTAGCCCTGAGGTTCTT TTCCCAGGATGGCTCCAGGATAAGGATCACTGTAGGTGGTTGTGGAGTTGACACCCC TGTTGACTCCTTCCCAGCTGATTGTCAGAGCCTTAGACCCAGCACGCCTTGGATTAG CTCTGCAGAGTGTCTTGGTTGAGAGAATAACCTCACCGTACCCACATGACACGTGAT TTGGAAAGAGACTAGAGGCCACACTTGATAAATCATGGGGAACAGATGTGTTCCACC CAACAAATGTGATAAGTGATCATGCAGCCAGAGCCAGCCTTCCTTCAATCAAGGTTT CCAGGCAGAGCAAATACCCTAGAGATTCTCTGTGATATAGGAAATTTGGATGAAGGG AGCTAGAAGAAATACAGGGATTTTTTTTTTTTTTTAAGATGGAGTCTTACTCTGTTG CTAGGCTGGAGTGCAGTGGTGCGATCTCAGCTCCCTGCAACCTCCACCTCCTGGGTT CAAACAATTCTCCTGCCTCAGCCTCCCGAGTACTGGGAATATAGGTGCACGCCACCA CACCCAACAAATTTTTGTACTTTTAGTACAGATGAGGGTTCACTATGTTGGCCAGGA TGGTCTCGATCTCTTGACCTCATGATCCACCCACCTCGGTCTCCCAAAGTGCTGGGA TTACAGGCTTGAGCCACCGGGTGACCGGCTTACAGGGATATTTTTAATCCCGTTATG GACTCTGTCTCCAGGAGAGGGGTCTATCCACCCCTGCTCATTGGTGGATGTTAAACC AATATTCCTTTCAACTGCTGCCTGCTAGGGAAAAACTACTCCTCATTATCATCATTA TTATTGCTCTCCACTGTATCCCCTCTACCTGGCATGTGCTTGTCAAGTTCTAGTTGT TCAATAAATTTGTTAATAATGCTGA(SEQIDNO:93) >NP_008979.3butyrophilinsubfamily3memberA1isoforma precursor[Homosapiens] MKMASFLAFLLLNFRVCLLLLQLLMPHSAQFSVLGPSGPILAMVGEDADLPCHLFPT MSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIH NVTASDSGKYLCYFQDGDFYEKALVELKVAALGSDLHVDVKGYKDGGIHLECRSTGW YPQPQIQWSNNKGENIPTVEAPVVADGVGLYAVAASVIMRGSSGEGVSCTIRSSLLG LEKTASISIADPFFRSAQRWIAALAGTLPVLLLLLGGAGYFLWQQQEEKKTQFRKKK REQELREMAWSTMKQEQSTRVKLLEELRWRSIQYASRGERHSAYNEWKKALFKPADV ILDPKTANPILLVSEDQRSVQRAKEPQDLPDNPERFNWHYCVLGCESFISGRHYWEV EVGDRKEWHIGVCSKNVQRKGWVKMTPENGFWTMGLTDGNKYRTLTEPRTNLKLPKP PKKVGVFLDYFTGDISFYNAVDGSHIHTFLDVSFSEALYPVFRILTLEPTALTICPA (SEQIDNO:94) Human >NM_007047.5Homosapiensbutyrophilinsubfamily3member BTN3A2 A2(BTN3A2),transcriptvariant1,mRNA GACTCTTACTGTTTCTCATGGTGAGAAGACAATATTTGCTTTCTCTTTTTCCTTTCT TCCGGATGAGAGGCTAAGCCATAATAGAAAGAATGGAGAATTATTGATTGACCGTCT TTATTCTGTGGGCTCTGATTCTCCAATGGGAATACCAAGGGATGGTTTTCCATACTG GAACCCAAAGGTAAAGACACTCAAGGACAGACATTTTTGGCAGAGCATAGATGAAAA TGGCAAGTTCCCTGGCTTTCCTTCTGCTCAACTTTCATGTCTCCCTCCTCTTGGTCC AGCTGCTCACTCCTTGCTCAGCTCAGTTTTCTGTGCTTGGACCCTCTGGGCCCATCC TGGCCATGGTGGGTGAAGACGCTGATCTGCCCTGTCACCTGTTCCCGACCATGAGTG CAGAGACCATGGAGCTGAAGTGGGTAAGTTCCAGCCTAAGGCAGGTGGTGAACGTGT ATGCAGATGGAAAGGAAGTGGAAGACAGGCAGAGTGCACCGTATCGAGGGAGAACTT CGATTCTGCGGGATGGCATCACTGCAGGGAAGGCTGCTCTCCGAATACACAACGTCA CAGCCTCTGACAGTGGAAAGTACTTGTGTTATTTCCAAGATGGTGACTTCTATGAAA AAGCCCTGGTGGAGCTGAAGGTTGCAGCACTGGGTTCTAATCTTCACGTCGAAGTGA AGGGTTATGAGGATGGAGGGATCCATCTGGAGTGCAGGTCCACCGGCTGGTACCCCC AACCCCAAATACAGTGGAGCAACGCCAAGGGAGAGAACATCCCAGCTGTGGAAGCAC CTGTGGTTGCAGATGGAGTGGGCCTATATGAAGTAGCAGCATCTGTGATCATGAGAG GCGGCTCCGGGGAGGGTGTATCCTGCATCATCAGAAATTCCCTCCTCGGCCTGGAAA AGACAGCCAGCATTTCCATCGCAGACCCCTTCTTCAGGAGCGCCCAGCCCTGGATCG CAGCCCTGGCAGGGACCCTGCCTATCTTGCTGCTGCTTCTCGCCGGAGCCAGTTACT TCTTGTGGAGACAACAGAAGGAAATAACTGCTCTGTCCAGTGAGATAGAAAGTGAGC AAGAGATGAAAGAAATGGGATATGCTGCAACAGAGCGGGAAATAAGCCTAAGAGAGA GCCTCCAGGAGGAACTCAAGAGGAAAAAAATCCAGTACTTGACTCGTGGAGAGGAGT CTTCGTCCGATACCAATAAGTCAGCCTGATGCTCTAATGGAAAAATGGCCCTCTTCA AGCCTGGTGAGGAAATGCTTCAGATGAGGCTCCACCTTGTTAAATAAATTGGATGTA TGGAAAAATAGACTGCAGAAAAGGGGAACTCATTTAGCTCACGAGTGGTCGAGTGAA GATTGAAAATTAACCTCTGAGGGCCAGCACAGCAGCTCATGCCTGTAATCCTAGCAC TTTGGAAGGCTGAGGAGGGCGGATCACAAGGTCAGGAGATCAAGACCATCCTGGCTA ACACGGTGAAACCCCGTCTCTACTAAAAATACAAAAAATAAAAAATTAGCCGGGCAT GGTGACGGGCACCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATGGCATG AACCCGGAAGGCAGAGCTTGCAGTGAGCCGAGATCACGCCACTGCACTCCAGCCTGG GAGACAGAGCGAGACTCTGTCTCAAGAAAAAAAAAAAAAAAAAAAAAGAAAAGAAAA TTAACCTCTGAGTATAAAGCATCAGTGGGCAGAATCAATGTGGGGAGGGAAACAACA AAAATGTAGAAAGAGGATCCTTGTTGCTTCTTGGGGCCGCATCAGGGTATTGGGTTA GGCAGATACTGACCTTACTTTCATTTCCCCTCTGGTCACTAGACCCCTGGGGCTTTC ACCAATGACATTGATGAGAGAATCACATTCAGGGCAGGCTAGGGACACGGGGTTCTG GAAGGACCTCCTCAGCATGGCCCAAGCCTTGCATGCTGTGGCTCTTAAATCCAGGAA AAATGGCTGACCCCATGGACACCTCCTCAAACTCTCTGCAGCAGATGTAATTCTGTA TCCAGACATGGCAAATGCCATCCTCCTTGTTTCTGAGGACCAGAGGAGTGTACAGCG TGCTGAGGAGCCCCATGACCTACCAGACAACCCTGAGAGATTTGAATGGCGTTACTG TGTGCTTGGCTGTGAAAGCTTCATGTCAGAGAGACACTACTGGGAGGTGGAAGTGGG GGACAGAAAAGAGTGGCATATTGGGGTATGTAGTAAGAACGTGGAGAGGAAAAAAGT TTGGGTCAAAATGACACCGGAGAACGGATACTGGACTATGGGCCTGACTGATGGGAA TAAGTATCGGGCTCTCACTGAGCCCAGAACCAACCTGAAACTTCCTGAGCCTCCTAG GAAAGTGGGGGTCATCCTGGACTATGAGACTGGACATATCTCGTTCTACAATGCCAC GGATGGATCTCATATCTACACATTTCTGCACGCCTCTTCCTCTGAGCCTCTGTATCC TGTATTCAGAATTTTGACCTTGGAGCCCACTGCCCTGACCGTTTGCCCAATACCAAA AGTAGAGAGTTCCCCCGATCCCGACCTAGTGCCTGATCATTCCCTGGAGATACCACT GACCCCAGGCTTAGCTAATGAAAGTGGGGAGCCTCAGGCTGAAGTAACATCTCTGCT TCTCCCTGCCCAGCCTGGAGCTAAGGGTCTCACCCTCCACAACAGCCAGTCAGAACC ATAAAGCTACAGGCACACACTGAAGCACTTTACTGATATTCATTCAATTATTCCATA GGACAGTTGTTTGAGTTTGGTGCCACCTTATTGGCCCCTTTATACAGATAAGGAAAC TGGGGTGTAGAAAAGTGTATTGACTTTACAAAGCAGACAGGAATAGTGAACAACAGA GCTGGGATCTGAACAACAATGACTAACATTAATGGAGAATTTAAAACGTTCTGAGTG CTGTGTTATGAGCTTTGGTGGGTGTCACTCCTTTAATCCTCACAACACCCTGTCAGG TAGTCTCATTTGGCAAGTATGGAAGCAGAGGCAGGGCAACATTAAGTAGCTTACATA ACTCACACGGTAATTTGTGCAGTTGGGAGATGTTCAGCTTCAGTCCCTGGCCAATTG CCCGTTCTTTTCCAGCCTGATTTTTCCTGCATGGGAAGAGCCCACATGTAGCCCTGA GGTTCCCTTCCCAGGACAGCTCCAGGATCGAGATCACTGTGAGTGGTTGTGGAGTTA AGACCCCTATGGACTCCTTCCCAGCTGATTATCAGAGCCTTAGACCCAGCACTCCTT GGATTGGCTCTGCAGAGTGTCTTGGTTGAGAGAATAACGTTGCAGTTCCCACAGGGC ATGTGACTTTGAAAGAGACTAGAGGCCACACTCAGTTAATAATGGGGCACAGATGTG TTCCCACCCAACAAATGTGATAAGTGATCGTGCAGCCAGAGCCAGCCTTCCTTCAGT CAAGGTTTCCAGGCAGAGCAAATACCCTAGAGATTCTCTGTAATATTGGTAATTTGG ATGAAGGAAGCTAGAAGAATTACAGGGATGTTTTTAATCCCACTATGGACTCAGTCT CCTGGAAAAGGATCTGTCCACTCCTGGTCATTGGTGGATGTTAAACCCATATTCCTT TCAACTGCTGCCTGCTAGGGAAAACTGCTCCTCATTATCATCACTATTATTGCTCAC CACTGTATCCCCTCTACTGGGCAAGTGCTTGTCAAGTTCTAGTTGTTCAATAAATTT GTTAATAATGCTGA(SEQIDNO:95) >NP_008978.2butyrophilinsubfamily3memberA2isoforma precursor[Homosapiens] MKMASSLAFLLLNFHVSLLLVQLLTPCSAQFSVLGPSGPILAMVGEDADLPCHLFPT MSAETMELKWVSSSLRQVVNVYADGKEVEDRQSAPYRGRTSILRDGITAGKAALRIH NVTASDSGKYLCYFQDGDFYEKALVELKVAALGSNLHVEVKGYEDGGIHLECRSTGW YPQPQIQWSNAKGENIPAVEAPVVADGVGLYEVAASVIMRGGSGEGVSCIIRNSLLG LEKTASISIADPFFRSAQPWIAALAGTLPILLLLLAGASYFLWRQQKEITALSSEIE SEQEMKEMGYAATEREISLRESLQEELKRKKIQYLTRGEESSSDINKSA(SEQID NO:96) Human >NM_007049.5Homosapiensbutyrophilinsubfamily2member BTN2A1 A1(BTN2A1),transcriptvariant1,mRNA AGATTTCGTTTCCTGCATCTCCAAACATGGCGACCTAGGAGAAGGGGAAGAACAATT TTTTCTCCTCTTTTGGGAAGGTTTGTGTCTAGTAGTGCCTGTGCCCCTGGGCAGATT GGAGAGAAGAGGGACGACTGGAGAATCGTCGAGAACCAGCGGAGAAAAGAAAAAGCA ACGTTTAATTCTAGAAGGCCTCCTGTCCCTGCCTGCTCTGGGTGCTCATGGAATCAG CTGCTGCCCTGCACTTCTCCCGGCCAGCCTCCCTCCTCCTCCTCCTCCTCAGCCTGT GTGCACTGGTCTCAGCCCAGTTTATTGTCGTGGGGCCCACTGATCCCATCTTGGCCA CGGTTGGAGAAAACACTACGTTACGCTGCCATCTGTCACCCGAGAAAAATGCTGAGG ACATGGAGGTGCGGTGGTTCCGGTCTCAGTTCTCCCCCGCAGTGTTTGTGTATAAAG GTGGCAGAGAGAGAACAGAGGAGCAGATGGAGGAGTACCGAGGAAGAACCACCTTTG TGAGCAAAGACATCAGCAGGGGCAGCGTGGCCCTGGTCATACACAACATCACAGCCC AGGAAAACGGCACCTACCGCTGTTACTTCCAAGAAGGCAGGTCCTACGATGAGGCCA TCCTGCACCTCGTAGTGGCAGGACTAGGCTCTAAGCCCCTCATTTCAATGAGGGGCC ATGAAGACGGGGGCATCCGGCTGGAGTGCATATCTAGAGGGTGGTACCCAAAGCCCC TCACAGTGTGGAGGGACCCCTACGGTGGGGTTGCGCCTGCCCTGAAAGAGGTCTCCA TGCCTGATGCAGACGGCCTCTTCATGGTCACCACGGCTGTGATCATCAGAGACAAGT CTGTGAGGAACATGTCCTGCTCTATCAACAACACCCTGCTCGGCCAGAAGAAAGAAA GTGTCATTTTTATTCCAGAATCCTTTATGCCCAGTGTGTCTCCCTGTGCAGTGGCCC TGCCTATCATTGTGGTTATTCTGATGATACCCATTGCCGTATGCATCTATTGGATCA ACAAACTCCAAAAGGAAAAAAAGATTCTGTCAGGGGAAAAGGAGTTTGAACGGGAAA CAAGAGAAATTGCTCTAAAGGAACTGGAGAAAGAACGTGTGCAAAAAGAGGAAGAAC TTCAAGTAAAAGAGAAACTTCAAGAAGAATTGCGATGGAGAAGAACATTCTTACATG CTGTTGATGTGGTCCTGGATCCAGACACCGCTCATCCCGATCTCTTCCTGTCAGAGG ACCGGAGAAGTGTGAGAAGGTGCCCCTTCAGGCACCTAGGGGAGAGCGTGCCTGACA ACCCAGAGAGATTCGACAGTCAGCCTTGTGTCCTAGGCCGGGAGAGCTTCGCTTCAG GGAAACATTACTGGGAGGTGGAGGTGGAAAACGTGATTGAGTGGACTGTGGGGGTCT GTAGAGACAGTGTTGAGAGGAAAGGGGAGGTCCTGCTGATTCCTCAGAATGGCTTCT GGACCTTGGAGATGCATAAAGGGCAATACCGGGCCGTGTCCTCCCCTGATAGGATTC TCCCTTTGAAGGAGTCCCTTTGCCGGGTGGGCGTCTTCCTGGACTATGAAGCTGGAG ATGTCTCCTTCTACAACATGAGGGACAGATCGCACATCTACACATGTCCCCGTTCAG CCTTTTCCGTGCCTGTGAGGCCCTTCTTCAGGTTGGGGTGTGAGGACAGCCCCATCT TCATCTGCCCTGCACTCACAGGAGCCAATGGGGTCACGGTGCCTGAAGAGGGCCTGA CACTTCACAGAGTGGGGACCCACCAGAGCCTATAGAATCAATTCCTTGGTCTCACAG CCATGTAGACAAGCCCTGGTCATCTCAGCAGCCACCGCACAACACCCCTGGTGGAAG ACACGCCCTCCTCCCCTCTGGTCACACAAGAGAACATCTTCCAGCTGCCTCTTTCAC ACCCACTACAGACCTCAGCCCCAGTTTTCTCCTCCTCACTAGGCTGTGTTTTTAGTA GTTCCTTTGCTTGTAACTATGGGATGGGATCCAGGCATAGGGAACTAGTTGTTACAC AGCTCCCAGCCAAGAAGAAAGTGTGAGAAGTTGATGGGCAGCAAACCTGCTGTTTAA CATCAGGGTGACCACATTAAGCCCAGTATTCCAGTTGGCACCAGAAGATATGGACTT GGAATGAGGCCTACAGGGTTCACCAGGATGTAAGAGGAGAGAGGAATCCACAGGACC ACCAGAGAGGAGAGGGAACCAGATATGCAGATCAGAGATAGAGGAAGTGGAACCAGA GAGCTGGGAGGGACCAAGGTTGTAAGGGTGGCTAAGTCCCACCATAACAGCTAAGGG GACCTGGGAGATGATGGCTCATTTCCACCCAGCCCCAGGATTTCCAGAGCGCACATC CACAGGCCTGGACCTGGGATGAAGATGAATGAAGAACATGGATGCACGTGGATGTAG TTTGGCTCAGGTGTCCCTGCAGTTGGCAAGGAGTCAGTACTCAGTCCCTGAGTGTGG CTGAAATTTGAGGTCCTGGCTGAGCCAAGGAGTAATGGACCAGATCTACCTCAGTAT TCAAGTTCAGTGGGGACACCAGTGGCTTCAAACTTCCTGGTTTCATGATATCTTGAG ACGCCTTACAAATGATGGAGGATTCCAAAGAGTTTTTGTTTATTTGGGTTAATATTT GTTGGTATTTATGGCATTTGAGATTGAAACTAAGAAATGTTTTAATTTATTACCTTT ACAACATTTATTTACATTACATACATACATTTACAACATTTATTAATTTATATTAAA ATAGCATGAATAAGCCAATTATAGGTTAATATAAGTAGAATGTTTGTGAAAAATAAG TATGGTATCCAAAGCAAAATAAATTTTATTGTGAAGTGTG(SEQIDNO:97) >NP_008980.1butyrophilinsubfamily2memberA1isoform1 precursor[Homosapiens] MESAAALHFSRPASLLLLLLSLCALVSAQFIVVGPTDPILATVGENTTLRCHLSPEK NAEDMEVRWFRSQFSPAVEVYKGGRERTEEQMEEYRGRTTFVSKDISRGSVALVIHN ITAQENGTYRCYFQEGRSYDEAILHLVVAGLGSKPLISMRGHEDGGIRLECISRGWY PKPLTVWRDPYGGVAPALKEVSMPDADGLFMVTTAVIIRDKSVRNMSCSINNTLLGQ KKESVIFIPESFMPSVSPCAVALPIIVVILMIPIAVCIYWINKLQKEKKILSGEKEF ERETREIALKELEKERVQKEEELQVKEKLQEELRWRRTFLHAVDVVLDPDTAHPDLF LSEDRRSVRRCPFRHLGESVPDNPERFDSQPCVLGRESFASGKHYWEVEVENVIEWT VGVCRDSVERKGEVLLIPQNGFWTLEMHKGQYRAVSSPDRILPLKESLCRVGVFLDY EAGDVSFYNMRDRSHIYTCPRSAFSVPVRPFFRLGCEDSPIFICPALTGANGVTVPE EGLTLHRVGTHQSL(SEQIDNO:98) Human >NM_001040462.3Homosapiensbutyrophilinlike8(BTNL8), BTNL8 transcriptvariant2,mRNA AGAACAGCGCAGTTTGCCCTCCGCTCACGCAGAGCCTCTCCGTGGCTTCCGCACCTT GAGCATTAGGCCAGTTCTCCTCTTCTCTCTAATCCATCCGTCACCTCTCCTGTCATC CGTTTCCATGCCGTGAGGTCCATTCACAGAACACATCCATGGCTCTCATGCTCAGTT TGGTTCTGAGTCTCCTCAAGCTGGGATCAGGGCAGTGGCAGGTGTTTGGGCCAGACA AGCCTGTCCAGGCCTTGGTGGGGGAGGACGCAGCATTCTCCTGTTTCCTGTCTCCTA AGACCAATGCAGAGGCCATGGAAGTGCGGTTCTTCAGGGGCCAGTTCTCTAGCGTGG TCCACCTCTACAGGGACGGGAAGGACCAGCCATTTATGCAGATGCCACAGTATCAAG GCAGGACAAAACTGGTGAAGGATTCTATTGCGGAGGGGCGCATCTCTCTGAGGCTGG AAAACATTACTGTGTTGGATGCTGGCCTCTATGGGTGCAGGATTAGTTCCCAGTCTT ACTACCAGAAGGCCATCTGGGAGCTACAGGTGTCAGCACTGGGCTCAGTTCCTCTCA TTTCCATCACGGGATATGTTGATAGAGACATCCAGCTACTCTGTCAGTCCTCGGGCT GGTTCCCCCGGCCCACAGCGAAGTGGAAAGGTCCACAAGGACAGGATTTGTCCACAG ACTCCAGGACAAACAGAGACATGCATGGCCTGTTTGATGTGGAGATCTCTCTGACCG TCCAAGAGAACGCCGGGAGCATATCCTGTTCCATGCGGCATGCTCATCTGAGCCGAG AGGTGGAATCCAGGGTACAGATAGGAGATACCTTTTTCGAGCCTATATCGTGGCACC TGGCTACCAAAGTACTGGGAATACTCTGCTGTGGCCTATTTTTTGGCATTGTTGGAC TGAAGATTTTCTTCTCCAAATTCCAGTGGAAAATCCAGGCGGAACTGGACTGGAGAA GAAAGCACGGACAGGCAGAATTGAGAGACGCCCGGAAACACGCAGTGGAGGTGACTC TGGATCCAGAGACGGCTCACCCGAAGCTCTGCGTTTCTGATCTGAAAACTGTAACCC ATAGAAAAGCTCCCCAGGAGGTGCCTCACTCTGAGAAGAGATTTACAAGGAAGAGTG TGGTGGCTTCTCAGAGTTTCCAAGCAGGGAAACATTACTGGGAGGTGGACGGAGGAC ACAATAAAAGGTGGCGCGTGGGAGTGTGCCGGGATGATGTGGACAGGAGGAAGGAGT ACGTGACTTTGTCTCCCGATCATGGGTACTGGGTCCTCAGACTGAATGGAGAACATT TGTATTTCACATTAAATCCCCGTTTTATCAGCGTCTTCCCCAGGACCCCACCTACAA AAATAGGGGTCTTCCTGGACTATGAGTGTGGGACCATCTCCTTCTTCAACATAAATG ACCAGTCCCTTATTTATACCCTGACATGTCGGTTTGAAGGCTTATTGAGGCCCTACA TTGAGTATCCGTCCTATAATGAGCAAAATGGAACTCCCATAGTCATCTGCCCAGTCA CCCAGGAATCAGAGAAAGAGGCCTCTTGGCAAAGGGCCTCTGCAATCCCAGAGACAA GCAACAGTGAGTCCTCCTCACAGGCAACCACGCCCTTCCTCCCCAGGGGTGAAATGT AGGATGAATCACATCCCACATTCTTCTTTAGGGATATTAAGGTCTCTCTCCCAGATC CAAAGTCCCGCAGCAGCCGGCCAAGGTGGCTTCCAGATGAAGGGGGACTGGCCTGTC CACATGGGAGTCAGGTGTCATGGCTGCCCTGAGCTGGGAGGGAAGAAGGCTGACATT ACATTTAGTTTGCTCTCACTCCATCTGGCTAAGTGATCTTGAAATACCACCTCTCAG GTGAAGAACCGTCAGGAATTCCCATCTCACAGGCTGTGGTGTAGATTAAGTAGACAA GGAATGTGAATAATGCTTAGATCTTATTGATGACAGAGTGTATCCTAATGGTTTGTT CATTATATTACACTTTCAGTAA(SEQIDNO:99) >NP_001035552.1butyrophilin-likeprotein8isoform2 precursor[Homosapiens] MALMLSLVLSLLKLGSGQWQVFGPDKPVQALVGEDAAFSCFLSPKTNAEAMEVRFFR GQFSSVVHLYRDGKDQPFMQMPQYQGRTKLVKDSIAEGRISLRLENITVLDAGLYGC RISSQSYYQKAIWELQVSALGSVPLISITGYVDRDIQLLCQSSGWFPRPTAKWKGPQ GQDLSTDSRTNRDMHGLFDVEISLTVQENAGSISCSMRHAHLSREVESRVQIGDTFF EPISWHLATKVLGILCCGLFFGIVGLKIFFSKFQWKIQAELDWRRKHGQAELRDARK HAVEVTLDPETAHPKLCVSDLKTVTHRKAPQEVPHSEKRFTRKSVVASQSFQAGKHY WEVDGGHNKRWRVGVCRDDVDRRKEYVTLSPDHGYWVLRLNGEHLYFTLNPRFISVF PRTPPTKIGVFLDYECGTISFFNINDQSLIYTLTCRFEGLLRPYIEYPSYNEQNGTP IVICPVTQESEKEASWQRASAIPETSNSESSSQATTPFLPRGEM(SEQIDNO: 100) Human >NM_006995.5Homosapiensbutyrophilinsubfamily2member BTN2A2 A2(BTN2A2),transcriptvariant1,mRNA GGGACTTTTTGGACACCCAGAGAACAGGTCCCAGATACCGAGTCCGCAACTCCAAAC ATCGCGATTAATAGGAGGCCTCTGGTCTCTGCCTGCCCTGGGTGCTCATGGAACCAG CTGCTGCTCTGCACTTCTCCCTGCCAGCCTCCCTCCTCCTCCTCCTGCTCCTCCTCC TTCTCAGCCTGTGTGCACTGGTCTCAGCCCAGTTTACTGTCGTGGGGCCAGCTAATC CCATCCTGGCCATGGTGGGAGAAAACACTACATTACGCTGCCATCTGTCACCCGAGA AAAATGCTGAGGACATGGAGGTGCGGTGGTTCCGGTCTCAGTTCTCCCCCGCAGTGT TTGTGTATAAGGGTGGGAGAGAGAGAACAGAGGAGCAGATGGAGGAGTACCGGGGAA GAATCACCTTTGTGAGCAAAGACATCAACAGGGGCAGCGTGGCCCTGGTCATACATA ACGTCACAGCCCAGGAGAATGGGATCTACCGCTGTTACTTCCAAGAAGGCAGGTCCT ACGATGAGGCCATCCTACGCCTCGTGGTGGCAGGCCTTGGGTCTAAGCCCCTCATTG AAATCAAGGCCCAAGAGGATGGGAGCATCTGGCTGGAGTGCATATCTGGAGGGTGGT ACCCAGAGCCCCTCACAGTGTGGAGGGACCCCTACGGTGAGGTTGTGCCCGCCCTGA AGGAGGTTTCCATCGCTGATGCTGACGGCCTCTTCATGGTCACCACAGCTGTGATCA TCAGAGACAAGTATGTGAGGAATGTGTCCTGCTCTGTCAACAACACCCTGCTCGGCC AGGAGAAGGAAACTGTCATTTTTATTCCAGAATCCTTTATGCCCAGCGCATCTCCCT GGATGGTGGCCCTAGCTGTCATCCTGACCGCATCTCCCTGGATGGTGTCCATGACTG TCATCCTGGCTGTTTTCATCATCTTCATGGCTGTCAGCATCTGTTGCATCAAGAAAC TTCAAAGGGAAAAAAAGATTCTGTCAGGGGAAAAGAAAGTTGAACAAGAGGAAAAAG AAATTGCACAGCAACTTCAAGAAGAATTGCGATGGAGAAGAACATTCTTACATGCTG CTGATGTGGTCCTGGATCCAGACACCGCTCATCCCGAGCTCTTCCTGTCAGAGGACC GGAGAAGTGTGAGGCGGGGCCCCTACAGGCAGAGAGTGCCTGACAACCCAGAGAGAT TCGACAGTCAGCCTTGTGTCCTGGGATGGGAGAGCTTCGCCTCAGGGAAACATTACT GGGAGGTGGAGGTGGAAAACGTGATGGTGTGGACTGTGGGGGTCTGCAGACACAGTG TTGAGAGGAAAGGGGAGGTCCTGCTGATTCCTCAGAATGGCTTCTGGACCCTGGAGA TGTTTGGAAACCAATACCGGGCCCTGTCCTCCCCTGAGAGGATTCTCCCTTTGAAGG AGTCCCTTTGCCGGGTGGGCGTCTTCCTGGACTATGAAGCTGGAGATGTCTCCTTCT ACAACATGAGGGACAGATCGCACATCTACACATGTCCCCGTTCAGCCTTTACTGTGC CTGTGAGGCCCTTCTTCAGGTTAGGGTCTGATGACAGCCCCATCTTCATCTGCCCTG CACTCACAGGAGCCAGTGGGGTCATGGTGCCTGAAGAGGGCCTGAAACTTCACAGAG TGGGGACCCACCAGAGCCTATAGAATCAATTCCTTGGACTCACAGCCATGCAGATAA GCCCTGGCCATCTCAGCAGCCACCGCACAACCCCCCTAATGAAAGACACGCCCTCCT CCCCTCTGGTCACGTAAGAGAACATCTTCCAGCTGCCTTTTTCACACCCACTCCAGC CCTCTGCCCCAGTTTTCTCCTCCTCACTAGTCTGTGGCTTTAGTAGTTCCTTTGCTT GTAATTATGGGATGGGATCCAGGCATAGGGAACTAGTTGTTTCATAGCTCCCAGTCA AAAAGAAAGTGAGAGAAGCTGTTGGGCAGCGAACCTACTGTTTAAAATCAGGATAAC CACATTAAGCCCAATATGCCAGTTGGCACCAGATGCTGTGGACTTGGAATGAGGCCA ACAGGGTTCACCAGGATGAGAGAGGAGAGAGGAATCCACAGGACCACCAGAAGGGAG AGGGAACCAGATATGCAGATCAGAGATAGAGGAAGTGGAACCAGAGAGCTGGGAGGG ACCAAGGTTGTAAGGATGGCTAAGTCCCACCATAAGAGCTAAAGGGTCCTGGGAGAT GATGGCTCATTTCCACCCAACCCCAGGATTTCCACAGCACACACCCACAGGCCTGGA CCTGGGATGAAGATGAATGAAGAACATGGACTCATGTGGATGTGGTTTGGCTCAGAT GTCCCTGCAATAAACAAGGGGTCAGTACTTAGTCCCTGAGTGTGGTTGAGGTTTGAG GTCCTGGTCGAGCAGGGCAGTACTGGACCAGGTCTACGTCAGCATTCAGGTTCAATG GGGACACCAGTGGCTTCAAACTTCCTGATCTAATTATGTTTTTAGACACTTAGAAGT TATTGAGGACTTTAAAGAGCTTTTGTTTATTTGGGTTAATATTTATGACATTTGACA TTGAAACAAAAATTTAAAATGTTATCTTTTAATTTATGTTAAAATAGCATTAATAAA TCAGTTATAGGTTAATGTAGATAGGATGTTTTGTGAAAAAGCAATCTATTGTGTCCA AATAAAAAAACAAAAAGTGTGACACTGGTTAACTTTTTCCAGATCTCATGTCTGGCT TAATAAGAGATATTTGTATTATCATATCTGCCTTTGTATTAAACCTATTGGTATATC ATAGGTCATGTTAGCTCAAAAAAACTTTACTGCACACTACTGAGAGAATGAGATGAA AAACGATTAATGTTTCATTATTATTATTGTGAAAATATTATTAACACTGGGGACTCC TTAAGAGTACATCAGAGTTCTCTCTAGGAATCCCAAAACCACATTTTGAAACTAGAA TAGTGGATCCTGGAAGTTAATCCATGTGCTGGTTAATTTTAGATGTCAACCTGACTG GATTAAGGAATACCTAGACAGCTGGTACAACATTATTTCTGGGTGTGTCTGTGAGTG TGTTTCCAGAAGAGATTGGCAAGTGAGTCAGTGGGAAATTCTCTCCTTCTGTTGGCT GGGTGCCCAATACAACAAAAAGGCAGAGGAAAGGCAAATTCTTCTCTCCTCTGGAGC TGAGACACTCTTCTTCTTCTGCCCTTGGACATCAGAACTCCTGGCTCTCCGGCCTTT GAACTTCAGGACTTGTACCAGGAGGCCCTGGGTTCTCAGGCCTTTGGCTTTGGACTG AGAGTTACACAATCAGCTTCCCTGGTTCTGAGGCTTTCAGACTTAAACTGAGCCATG CTACCAGCATCCCAGGGTCTCCAGCCTACAGATGAGCTGTTGTGCGATTTCTTAGCC TCCATAATCACATGAGCCAATCTCCTTAATAAATGCCTGCTCATAGATCTGTATCTA CATCTATATCTGTATGTGCATCTATATCTATGCCTATATCTATATCTATATCATATT GATTTTGTCTCTCTGGAGAACCCTGACTAATAAAATGAGGCATCTAAAA(SEQID NO:101) >NP_008926.2butyrophilinsubfamily2memberA2isoforma precursor[Homosapiens] MEPAAALHFSLPASLLLLLLLLLLSLCALVSAQFTVVGPANPILAMVGENTTLRCHL SPEKNAEDMEVRWFRSQFSPAVFVYKGGRERTEEQMEEYRGRITFVSKDINRGSVAL VIHNVTAQENGIYRCYFQEGRSYDEAILRLVVAGLGSKPLIEIKAQEDGSIWLECIS GGWYPEPLTVWRDPYGEVVPALKEVSIADADGLFMVTTAVIIRDKYVRNVSCSVNNT LLGQEKETVIFIPESFMPSASPWMVALAVILTASPWMVSMTVILAVFIIFMAVSICC IKKLQREKKILSGEKKVEQEEKEIAQQLQEELRWRRTFLHAADVVLDPDTAHPELFL SEDRRSVRRGPYRQRVPDNPERFDSQPCVLGWESFASGKHYWEVEVENVMVWTVGVC RHSVERKGEVLLIPQNGFWTLEMFGNQYRALSSPERILPLKESLCRVGVFLDYEAGD VSFYNMRDRSHIYTCPRSAFTVPVRPFFRLGSDDSPIFICPALTGASGVMVPEEGLK LHRVGTHQSL(SEQIDNO:102) Mouse >NM_175938.3Musmusculusbutyrophilin,subfamily2, BTN2A2 memberA2(Btn2a2),transcriptvariant1,mRNA GAAATTGTGAGACTTGCACGCGGAATGGGTCCTCCGAGGTCTGCTGTCGCGAGTCCC AGCACTTTGCAAGTAATGGAGAACAGAAAATTCTTTCCTCTCTACTGTAGCAGTTTG TTCTCTGGTGGCGACTGTGCTCAGCGACAAGTTGGAGAGTAGAGAAAAGGCAAGATA ATCAGCATTTGAGGGTCAGAGAAGAAAAGAAAACGCAGTTAATTCTAGAAGGTTTTC TGTCCACACGTGACCTAGGTGACTCTGTCCTGAAGACCTATGGAGCCTACAACTTCC CTGCGTTCTTGCCCGATAGCCTCCCTTCTCTTCTTCTTGGTCCTCAGCCTGTTTGTG CTGGTCTCAGCCCAGTTTACTGTCATAGGACCAGCTGAGCCCATCCTGGCCATGGTA GGAGAGAATACCACACTACACTGCCACCTGTCACCAGAGAGAAATGCCGAAGAGATG GAGGTGCGGTGGTTCCGGTGGCGTTTCTTCCCTGCAGTGCTGGTGTACAGAGGCCAT CAAGAGAGACCAGAGGAGCAGATGGTGGCATACCGAGGAAGAACCACCTTCATGCGC ACAGACATCAGCAAGGGAAGAGTTGCGCTCATTATCCACAATGTCACAGCCTATGAC AATGGCATCTACTGCTGTTACTTCCAGGAAGGCAGGTCCTATGACCAGGCAACCATG AAGCTTATGGTGGCAAGCCTTGGCTCTGAGCCACTTATTAAAATGAAGACACTTGAG GATGGGAGCATCTTGCTAGAGTGCACATCTGAAGGGTGGTACCCAGAGCCCCGAGCT GTGTGGAGAGACCCCTATGATGAAGTTGTACCTGCCCTGGAGGAGGAGTATACAGCT GACAGAGAAGGCCTCTTCACAGTCACCATGACTATAATCATCAGGGACTGCTCTGTG AGGAACATGACCTGCTCTGTCAATAACACTCTGCTCAGCCAGGAGGTGGAAAGTGTG ATTCTCATTCCAGAATCCTTCGTGCCCAGCCTTCCTCTGTGGATGGTGGCTGTGGCT GTCACTCTGCCTGTAGTAATGCTGATTCTCCTCACATCTGGAAGCATCTGCCTTGTC AAGAAACACCGCAGGAAGAAATCTATTCTGTCAGCTGAAAAAGAAGCCGAATATGAA GAGAAGGAAGCTGCACGGCAACTTCAAGAGGAACTGCGATGGAGACGAACCCTCTTA CATGCTGCTGACGTGGTCCTGGACCCAGATACAGCTCATCCTGAGCTCTTCCTGTCA GATGACCAGAGAAGTGTAATACGAGGCTCTTCGAGGCAGAGTGTGCCTGACAACCCT GAGAGATTTGACTGCCGTCCATGTGTCCTGGGCAGGGAAAGCTTCTCCTCAGGGAAG CATTACTGGGAGGTGGAGGTGGAAAATGTAATGGTGTGGGCCATTGGTGTTTGTAGA GACAGCGTGGAAAGGAAAGGGGAGGCCCTGTTGGTTCCTCAGAATGGCTTCTGGACC CTGGAGATGTTTGGAAGCCAGTATCGAGCCCTGTCCTCCCCAGAAAAGATCATACCT CTGAAAGAGCGTCTTCACCGTATAGCTGTCTTCCTGGACTGTGAGGGTGGAGATATT TCTTTCTACAACATGAGAGACAGATCACACATTTACACATGTCCTCCTGTGACTTTC ACTGGGCCCCTGAGACCCTTCTTTAGGCTTGGTTCTGATGACAGTCCCCTGTTCATC TGTCCAGCATTCACAGGGGCACAGGGAGTTACAATACCTGAGGGTGGCTTATTCCTA TATAAGACAAGACCAATTTCTCAGAGCCTTGTAAGGAAGCCATAGCTCTCTACACAG TACCATCTGTTGGAGACTAGACCCCATGTCCTTCAGATCACATGGAGCATCTTCCAG CTGCCACCTTCACACATACTTCAGGCCCAGTCCTCAGATTACTACATCATTTCTTCT AACTATGGGCCTAGGTAGAGCCAGTCTTAGGGGACTATTGCTGTAATACAGCTCTCT CCTGAGAAGAAAGTGTGAGAAGGGCAGAAAACTTGGAGTTTCAACATGCTGCTCTGG TCACAGTGGATATCAGGCAAGAGCAACAGGGTGGATCAGGATGTAAGAAGTGAGAAC TACAGAGGAAGGAGACAGATAAAGATGAATTGAGGCCGAAGATGGAGGAAATGGACT GAAGAGCTCTGGGGTAAGCCCTATGTGACAGCTGTGGATAGGTAGGAGCTAATGGTC CATTGATATCCAAAGCCAAAGATTTAAATATCACATAGTGTGTCTGGAGTGTATATC TGTAGACCTACACATGAGAGGAAACAATCATAGTGATGAACTGGATGTAAGCTGGCT CAGACGTCCCTACAATAAACACTTCTGAGTTCCATGTCTGTGCTCAGTAAGAATGGC TTGAGGCTTGCGGTCCATGCTGAGCAGCCAGGTCCACATGAATCGGATTTACTAGAG TAGGTAGCAGTTCAAGTTCCTTAGGCTCAGGATGTCTTCCTTTCCCCCAAGCCCTTC CCCCTTCAAGATAGGTCTCACTATGTAGACCAGGCCAGCCTCCACCTCCAGAGTTCT GGGATTAAAGACAAGCACAACCATGTCCAGTTTATGAGCTTGTGATATATACAGAAG ATTAAGTTCTGTGTTCTTGGGTTAGTAACTGTTGAGATTTGTTTTGAGTCATGCTCT CACTGGCTAGCACTGCTCTTGACTTTCTCTCCCCATCTTTTTGTTATTGCTTTTCAA GACATGGTTTCACTGTGTATTTCTGGCTGATAAGCTGATTTTGAATTCACAGAGATC TGCCTCTGCCTCCTGAGTGCTGGGATTAAAGGTGTGTTACACTACGCCTGGCTTCAC TCTATCTCTTCAGTGTGGGGATTATAGGTTTATACTATCATGCCTAACTAATGTCTG TTGCTGCATATGACATTTGAACTTTAGAACAGAAAAACAACTATACATATTAATATA TATTAAACTAATAATAAGC(SEQIDNO:103) >NP_787952.2butyrophilinsubfamily2memberA2isoform1 precursor[Musmusculus] MEPTTSLRSCPIASLLFFLVLSLFVLVSAQFTVIGPAEPILAMVGENTTLHCHLSPE RNAEEMEVRWFRWRFFPAVLVYRGHQERPEEQMVAYRGRTTFMRTDISKGRVALIIH NVTAYDNGIYCCYFQEGRSYDQATMKLMVASLGSEPLIKMKTLEDGSILLECTSEGW YPEPRAVWRDPYDEVVPALEEEYTADREGLFTVTMTIIIRDCSVRNMTCSVNNTLLS QEVESVILIPESFVPSLPLWMVAVAVTLPVVMLILLTSGSICLVKKHRRKKSILSAE KEAEYEEKEAARQLQEELRWRRTLLHAADVVLDPDTAHPELFLSDDQRSVIRGSSRQ SVPDNPERFDCRPCVLGRESFSSGKHYWEVEVENVMVWAIGVCRDSVERKGEALLVP QNGFWTLEMFGSQYRALSSPEKIIPLKERLHRIAVFLDCEGGDISFYNMRDRSHIYT CPPVTFTGPLRPFFRLGSDDSPLFICPAFTGAQGVTIPEGGLFLYKTRPISQSLVRK P(SEQIDNO:104) Human >NM_001732.3Homosapiensbutyrophilinsubfamily1member BTN1A1 A1(BTN1A1),mRNA AGCTTTCTCACTTGGTAGCAGTGGCCTCTTGTGCCTTTTTCTCCAAGATCACCCAGG CTGAAGCTCCTGAGGGGACTCACATCAGTTATCTTGCTGCTCCAGAAGGGTGGGAGA TGGCAGTTTTCCCAAGCTCCGGTCTCCCCAGATGTCTGCTCACCCTCATTCTCCTCC AGCTGCCCAAACTGGATTCAGCTCCCTTTGACGTGATTGGACCCCCGGAGCCCATCC TGGCCGTTGTGGGTGAGGACGCCGAGCTGCCCTGTCGCCTGTCTCCGAACGCGAGCG CCGAGCACTTGGAGCTACGCTGGTTCCGAAAGAAGGTTTCGCCGGCCGTGCTGGTGC ATAGGGACGGGCGCGAGCAGGAAGCCGAGCAGATGCCCGAGTACCGCGGGCGGGCGA CGCTGGTCCAGGACGGCATCGCCAAGGGGCGCGTGGCCTTGAGGATCCGTGGCGTCA GAGTCTCTGACGACGGGGAGTACACGTGCTTTTTCAGGGAGGATGGAAGCTACGAAG AAGCCCTGGTGCATCTGAAGGTGGCTGCTCTGGGCTCTGACCCTCACATCAGTATGC AAGTTCAAGAGAATGGAGAAATCTGTCTGGAGTGCACCTCAGTGGGATGGTACCCAG AGCCCCAGGTGCAGTGGAGAACTTCCAAGGGAGAGAAGTTTCCATCTACATCAGAGT CCAGGAATCCTGATGAAGAAGGTTTGTTCACTGTGGCTGCTTCAGTGATCATCAGAG ACACTTCTGCGAAAAATGTGTCCTGCTACATCCAGAATCTCCTTCTTGGCCAGGAGA AGAAAGTAGAAATATCCATACCAGCTTCCTCCCTCCCAAGGCTGACTCCCTGGATAG TGGCTGTGGCTGTCATCCTGATGGTTCTAGGACTTCTCACCATTGGGTCCATATTTT TCACTTGGAGACTATACAACGAAAGACCCAGAGAGAGGAGGAATGAATTCAGCTCTA AAGAGAGACTCCTGGAAGAACTCAAATGGAAAAAGGCTACCTTGCATGCAGTTGATG TGACTCTGGACCCAGACACAGCTCATCCCCACCTCTTTCTTTATGAGGATTCAAAAT CTGTTCGACTGGAAGATTCACGTCAGAAACTGCCTGAGAAAACAGAGAGATTTGACT CCTGGCCCTGTGTGTTGGGCCGTGAGACCTTCACCTCAGGAAGGCATTACTGGGAGG TGGAGGTGGGAGACAGGACTGACTGGGCAATCGGCGTGTGTAGGGAGAATGTGATGA AGAAAGGATTTGACCCCATGACTCCTGAGAATGGGTTCTGGGCTGTAGAGTTGTATG GAAATGGGTACTGGGCCCTCACTCCTCTCCGGACCCCTCTCCCATTGGCAGGGCCCC CACGCCGGGTTGGGATTTTCCTAGACTATGAATCAGGAGACATCTCCTTCTACAACA TGAATGATGGATCTGATATCTATACTTTCTCCAATGTCACTTTCTCTGGCCCCCTCC GGCCCTTCTTTTGCCTATGGTCTAGCGGTAAAAAGCCCCTGACCATCTGCCCAATTG CTGATGGGCCTGAGAGGGTCACAGTCATTGCTAATGCCCAGGACCTTTCTAAGGAGA TCCCATTGTCCCCCATGGGGGAGGACTCTGCCCCTAGGGATGCAGACACTCTCCATT CTAAGCTAATCCCTACCCAACCCAGCCAAGGGGCACCTTAAGGAATATCTCAGCTCA TCTGTTTTCCTTTCCTCTAACCCCTCTCCTCCATAGCCTTCTGAGGCTTCACCTGCT AGCTTTACCCAGTCTGTTTCTTCCTGTTGGGTGGCAATTAATTAATCCTGTGAAGGT TACATTGCTGCTGCTAGAGAGGGTGGGGATTGCACCTTCCAAATCTGTTTCTGTACC AATATTTGGGGGATGGAGGGGTGACTCAAACTGCTTCTAGTGTTCTCCTAATCCCTT AAGACTAGAACCTATAGGAAACTACTTGGAGCAAACTCAAAGGACAGATTAGGGATC GAGATTGGGTCAGGTTAGCATGGGGTTGTGGTTGAAATATCTTGGTATCCAGGATAA GGGTATGTGGAAAAACAGGCTTTAGGCAAGTGGAAAATTCAAAATGTGCTGTGAAAG GACAATCTCAGGCTGAAATCCCATAAAGGAACTTGGAGGGAATATTATGATGGAGGG AAGTGAGGTGAATCCAGGCACATGATGAACACCTGGCTCATCCATAGAGTTTTCACA GCCTATATCGCAAATTTTCTAAGCCACGTCCTATAGGACAGAGGAGACTGGCCCCAC TTCTATGGGTCTGAGCTGTGGAAAAGGGAGAGCAGAGAGGAACTGAGATGAGCAGGG ATGAAGGGTCAGGCAGAAAGCGTGATAGAGGAGAGAATTTTTGACAAAACTCAAAAG TTGTTTGCACAGCTGTTCTTTGTACCCTGTTCCTTTCTCTGCGCCCTCCTGTTTCTC CCTTGCCTGGAAGTCATTCCACCCTCAATTTGTTGATCCACAAGTTTCCAGTTGTCC TCTTCTTTTTGTTATAGCATCTCTCTATTTCAAAGACATTCCTAGAAGTCATCCTTC AGTGATATCACCACTTGCTCAGTCACCATCTCAACCTTATGTCACCTCAGCCCTCAT CTCAATGCCCAAACCCCTTACACACACCTTCAGTTAGCTTCAACTGCCTCCGTTTCC ACACTGTGCACCTTTCACTTTCCCTACCCAGCTTTCCTACATGCTGCCTCTCCTCAG GGTCCCCTGAATGCTGCATCATTGTGTTCAGTGCAGCTGGACTGATTGCACCTGTGT ATTTGCCCCTGAGCACTTTCCTTTACACATGTGGCTTGTCTTGCCAATAGACTCCAG GCTTATACCTTCCATTTCCATCGTATTCTCCAGTTTCCAGGATAGACGTTGCTCATC GTCTTTACCTAATAAATAAGTTTGTCTGATTGCTGAAA(SEQIDNO:105) >NP_001723.2butyrophilinsubfamily1memberA1precursor [Homosapiens] MAVFPSSGLPRCLLTLILLQLPKLDSAPFDVIGPPEPILAVVGEDAELPCRLSPNAS AEHLELRWFRKKVSPAVLVHRDGREQEAEQMPEYRGRATLVQDGIAKGRVALRIRGV RVSDDGEYTCFFREDGSYEEALVHLKVAALGSDPHISMQVQENGEICLECTSVGWYP EPQVQWRTSKGEKFPSTSESRNPDEEGLFTVAASVIIRDTSAKNVSCYIQNLLLGQE KKVEISIPASSLPRLTPWIVAVAVILMVLGLLTIGSIFFTWRLYNERPRERRNEFSS KERLLEELKWKKATLHAVDVTLDPDTAHPHLFLYEDSKSVRLEDSRQKLPEKTERFD SWPCVLGRETFTSGRHYWEVEVGDRTDWAIGVCRENVMKKGFDPMTPENGFWAVELY GNGYWALTPLRTPLPLAGPPRRVGIFLDYESGDISFYNMNDGSDIYTFSNVTFSGPL RPFFCLWSSGKKPLTICPIADGPERVTVIANAQDLSKEIPLSPMGEDSAPRDADTLH SKLIPTQPSQGAP(SEQIDNO:106) Mouse >NM_013483.3Musmusculusbutyrophilin,subfamily1, BTN1A1 memberA1(Btn1a1),mRNA AACAGCACACAGCCTTCTTCCTTCTGAAGAGCTCTCTCTTTGGCCCCGGGGTGACAA GCAGCCCTTTTCACTTGATCACTGTGGCTCTGGCTCCCTTTTCCTCTGGGTCTGTCG AAATCGCCTGAAGCTCTTGGCGGGCTTCATTGCCCCAGTTAGCTCAGAGATGGCAGT TCCCACCAACTCCTGCCTCCTGGTCTGTCTGCTCACCCTCACTGTCCTACAGCTGCC CACGCTGGATTCGGCAGCTCCCTTCGATGTGACCGCACCTCAGGAGCCAGTGTTGGC CCTAGTGGGCTCAGATGCCGAGCTGACCTGTGGCTTTTCCCCAAACGCGAGCTCAGA ATACATGGAGCTGCTGTGGTTTCGACAGACGAGGTCGACAGCGGTACTTCTATACCG GGATGGCCAGGAGCAGGAGGGCCAGCAGATGACGGAGTACCGCGGGAGGGCGACGCT GGCGACAGCCGGGCTTCTAGACGGCCGCGCTACTCTGCTGATCCGAGATGTCAGGGT CTCAGACCAGGGGGAGTACCGGTGCCTTTTCAAAGACAACGACGACTTCGAGGAGGC CGCCGTATACCTCAAAGTGGCTGCTGTGGGTTCAGATCCTCAAATCAGTATGACGGT TCAAGAGAATGGAGAAATGGAGCTGGAGTGCACCTCCTCTGGATGGTACCCAGAGCC TCAGGTGCAGTGGAGAACAGGCAACAGAGAGATGCTACCATCCACGTCAGAGTCCAA GAAGCATAATGAGGAAGGCCTGTTCACTGTGGCAGTTTCAATGATGATCAGAGACAG CTCCATAAAGAACATGTCCTGCTGCATCCAGAATATCCTCCTTGGCCAGGGGAAGGA AGTAGAGATCTCCTTACCAGCTCCCTTCGTGCCAAGGCTGACTCCCTGGATAGTAGC TGTGGCTATCATCTTACTGGCCTTAGGATTTCTCACCATTGGGTCCATATTTTTCAC TTGGAAACTATACAAGGAAAGATCCAGTCTGCGGAAGAAGGAATTTGGCTCTAAAGA GAGACTTCTGGAAGAACTCAGATGCAAAAAGACTGTACTGCATGAAGTTGACGTGAC TCTGGATCCAGACACAGCCCACCCCCACCTCTTCCTGTATGAAGATTCAAAGTCAGT TCGATTGGAAGATTCACGTCAGATCCTGCCTGATAGACCAGAGAGATTTGACTCCTG GCCCTGTGTGTTGGGCCGTGAGACCTTTACTTCAGGGAGACATTACTGGGAGGTGGA GGTGGGAGATAGAACTGACTGGGCCATTGGTGTGTGTAGGGAGAATGTGGTGAAGAA AGGGTTTGACCCCATGACTCCTGATAATGGGTTCTGGGCTGTGGAGTTGTATGGAAA TGGGTACTGGGCCCTCACCCCACTCAGGACCTCTCTCCGATTAGCAGGGCCCCCTCG CAGAGTTGGGGTTTTTCTGGACTATGACGCAGGAGACATTTCCTTCTACAACATGAG TAACGGATCTCTTATCTATACTTTCCCTAGCATCTCTTTCTCTGGCCCCCTCCGTCC CTTCTTTTGTCTGTGGTCCTGTGGTAAAAAGCCCCTGACCATCTGTTCAACTGCCAA TGGGCCTGAGAAAGTCACAGTCATTGCTAATGTCCAGGACGACATTCCCTTGTCCCC GCTGGGGGAAGGCTGTACTTCTGGAGACAAAGACACTCTCCATTCTAAACTGATCCC GTTCTCACCTAGCCAAGCGGCACCATAACAAATATTCCAGCTTCACGACTTTGCCTT CCTTTGACTAATCCCTCATGCCCCGAAGCTTCAGCTGTTGGCTTCTTGCAGCCCTGC TTCTTCCTGGTGGATGGAGATTAATTCACATTGGGAAGGTTAGGTATGTTGCTGCCA GACAAGGCAGGAAGAAAGGCCATCCTAGTTTGTTTCTGTACTAACAGTGGGGAGGAA GAGAGCTGAATCCTAAACTATTTCCAGTGCTCATATTCCTTCAGGCCAGAGCCTATA GAGAAGGATTTGGTACAATCACTCGAGGGATCAAGAGGCAATTAGGTTGGCATGGAA TTATGGCAGAAACATCTGGAATAGGGGTATGTGGAATGACAGGTTTTAGGTAAGGGA GAACAAAACCAAACCATAGGATGCTGAGAAAGAAAGATCTTGGACTAAACTCCTAAA AAAGCACTTAGAGAAGATATGACAGGCAAATGAAGTGAATTTGGTCTAATTTGATAC ACTTGCCCTGTCCCTAGGGTTTTTCAGTTATATCTCAATTTTTTTGTTGTTAATTAC ATTTTTGACAGCTTCATACATGTATATAATGCATTCTAATTACTCTCACTCTCCTCT ATTCTGTCTTATTTCCCTCCCCTCCCCTCATACCTTCCTTCTTGCTTCAAACCTGGC ACACTGAGTTTAATGGGCTATCATGGGAACATGGATTTAGAGCTTTCCTCTGAGCTC AAGAGAGCAGGTGTGACTGAATACAGTGATTTCCCCTCTCCTACAATCAATCAGCAG TCAATAGCTCAGCTGGGAGGGGTAGGGCCTCATGAGACTTCCCCTATCAAGGCTAAA TGTTGAAAGGGCCAGTTTTTAGCACCTGTGAGATCATGATTGCAAGAGCCCAGAAGA CAGCATTGCTCGGTCATTCTCCCTACCCTTTGGCTTTTCTGGTCTTTTGTCCTCTCT TTCAGGATGTGTCTGAACTCTGTATCTTAAGTTTTCTATGTCATGTTCTATAAGATA GAGGAGACTGGCCCTGCTTGTTTGAGAGCAATGTGAGCAAGCTAGCAAGAGACAGAA AGGAGCGGAGATGAATAGGGGTAGAGAAAATTTTTAAACAAACCCTCCAGGTGTGTG TGTGTGTGTGTGTGTCTTCCTCTTTTTTGACCTCCCTAAAGGTCAATCCAACCTCAC ATTATTGACTCCACTAGGTGGGGGTTCTGTGTGTGTGTGTGTGTGTGTGTGTGTGTG TGTGTGTGTTTTAAGATAGAGGTTTACTATGTAGCTTAGGCTGGCTTTGAATTCCTG ATCCTCCTGCCTCTACCTTCCAAGTGCTGGAAACATAGCCACATCCACCACCCCTAT CCAGTCCACCTGGTTTGATTCAGCAACGCTCAGGTAGCATCGCTGTTTGATCTGGAG CTGCCAGCTCCCTCGGCCCCCACTGCAATGCTTAACCCCCTCACAGGCACCTTCCCT TGCCTAACACTGCCATCCTTTTCCACACTGAGCCATTTGCTCAATGTAGCCTACCCA GGTATCCTGCTTTCTGGTCCCCAAAGTTACACCATGATGCTCAGCACAGCTGGACAG TTTGTCCCAATTTGTGTGTGTCCTCCTGTTTGTATGGGACTTCTTTTTGTCAATGGC CTGTGTGTGTATCCAAGCTCTTCCACTTCTATTGTATTTTTCCGGCTTCTAAAACAG ATGTTACCAAATAAAGAAAGAGAAAGAAAAAAAA(SEQIDNO:107) >NP_038511.1butyrophilinsubfamily1memberA1precursor [Musmusculus] MAVPTNSCLLVCLLTLTVLQLPTLDSAAPFDVTAPQEPVLALVGSDAELTCGFSPNA SSEYMELLWFRQTRSTAVLLYRDGQEQEGQQMTEYRGRATLATAGLLDGRATLLIRD VRVSDQGEYRCLFKDNDDFEEAAVYLKVAAVGSDPQISMTVQENGEMELECTSSGWY PEPQVQWRTGNREMLPSTSESKKHNEEGLFTVAVSMMIRDSSIKNMSCCIQNILLGQ GKEVEISLPAPFVPRLTPWIVAVAIILLALGFLTIGSIFFTWKLYKERSSLRKKEFG SKERLLEELRCKKTVLHEVDVTLDPDTAHPHLFLYEDSKSVRLEDSRQILPDRPERF DSWPCVLGRETFTSGRHYWEVEVGDRTDWAIGVCRENVVKKGFDPMTPDNGFWAVEL YGNGYWALTPLRTSLRLAGPPRRVGVFLDYDAGDISFYNMSNGSLIYTFPSISFSGP LRPFFCLWSCGKKPLTICSTANGPEKVTVIANVQDDIPLSPLGEGCTSGDKDTLHSK LIPFSPSQAAP(SEQIDNO:108) HumanTIGIT >NM_173799.4HomosapiensTcellimmunoreceptorwithIg andITIMdomains(TIGIT),mRNA ACATCTGCTTCCTGTAGGCCCTCTGGGCAGAAGCATGCGCTGGTGTCTCCTCCTGAT CTGGGCCCAGGGGCTGAGGCAGGCTCCCCTCGCCTCAGGAATGATGACAGGCACAAT AGAAACAACGGGGAACATTTCTGCAGAGAAAGGTGGCTCTATCATCTTACAATGTCA CCTCTCCTCCACCACGGCACAAGTGACCCAGGTCAACTGGGAGCAGCAGGACCAGCT TCTGGCCATTTGTAATGCTGACTTGGGGTGGCACATCTCCCCATCCTTCAAGGATCG AGTGGCCCCAGGTCCCGGCCTGGGCCTCACCCTCCAGTCGCTGACCGTGAACGATAC AGGGGAGTACTTCTGCATCTATCACACCTACCCTGATGGGACGTACACTGGGAGAAT CTTCCTGGAGGTCCTAGAAAGCTCAGTGGCTGAGCACGGTGCCAGGTTCCAGATTCC ATTGCTTGGAGCCATGGCCGCGACGCTGGTGGTCATCTGCACAGCAGTCATCGTGGT GGTCGCGTTGACTAGAAAGAAGAAAGCCCTCAGAATCCATTCTGTGGAAGGTGACCT CAGGAGAAAATCAGCTGGACAGGAGGAATGGAGCCCCAGTGCTCCCTCACCCCCAGG AAGCTGTGTCCAGGCAGAAGCTGCACCTGCTGGGCTCTGTGGAGAGCAGCGGGGAGA GGACTGTGCCGAGCTGCATGACTACTTCAATGTCCTGAGTTACAGAAGCCTGGGTAA CTGCAGCTTCTTCACAGAGACTGGTTAGCAACCAGAGGCATCTTCTGGAAGATACAC TTTTGTCTTTGCTATTATAGATGAATATATAAGCAGCTGTACTCTCCATCAGTGCTG CGTGTGTGTGTGTGTGTGTATGTGTGTGTGTGTTCAGTTGAGTGAATAAATGTCATC CTCTTCTCCATCTTCATTTCCTTGGCCTTTTCGTTCTATTCCATTTTGCATTATGGC AGGCCTAGGGTGAGTAACGTGGATCTTGATCATAAATGCAAAATTAAAAAATATCTT GACCTGGTTTTAAATCTGGCAGTTTGAGCAGATCCTATGTCTCTGAGAGACACATTC CTCATAATGGCCAGCATTTTGGGCTACAAGGTTTTGTGGTTGATGATGAGGATGGCA TGACTGCAGAGCCATCCTCATCTCATTTTTTCACGTCATTTTCAGTAACTTTCACTC ATTCAAAGGCAGGTTATAAGTAAGTCCTGGTAGCAGCCTCTATGGGGAGATTTGAGA GTGACTAAATCTTGGTATCTGCCCTCAAGAACTTACAGTTAAATGGGGAGACAATGT TGTCATGAAAAGGTATTATAGTAAGGAGAGAAGGAGACATACACAGGCCTTCAGGAA GAGACGACAGTTTGGGGTGAGGTAGTTGGCATAGGCTTATCTGTGATGAAGTGGCCT GGGAGCACCAAGGGGATGTTGAGGCTAGTCTGGGAGGAGCAGGAGTTTTGTCTAGGG AACTTGTAGGAAATTCTTGGAGCTGAAAGTCCCACAAAGAAGGCCCTGGCACCAAGG GAGTCAGCAAACTTCAGATTTTATTCTCTGGGCAGGCATTTCAAGTTTCCTTTTGCT GTGACATACTCATCCATTAGACAGCCTGATACAGGCCTGTAGCCTCTTCCGGCCGTG TGTGCTGGGGAAGCCCCAGGAAACGCACATGCCCACACAGGGAGCCAAGTCGTAGCA TTTGGGCCTTGATCTACCTTTTCTGCATCAATACACTCTTGAGCCTTTGAAAAAAGA ACGTTTCCCACTAAAAAGAAAATGTGGATTTTTAAAATAGGGACTCTTCCTAGGGGA AAAAGGGGGGCTGGGAGTGATAGAGGGTTTAAAAAATAAACACCTTCAAACTAACTT CTTCGAACCCTTTTATTCACTCCCTGACGACTTTGTGCTGGGGTTGGGGTAACTGAA CCGCTTATTTCTGTTTAATTGCATTCAGGCTGGATCTTAGAAGACTTTTATCCTTCC ACCATCTCTCTCAGAGGAATGAGCGGGGAGGTTGGATTTACTGGTGACTGATTTTCT TTCATGGGCCAAGGAACTGAAAGAGAATGTGAAGCAAGGTTGTGTCTTGCGCATGGT TAAAAATAAAGCATTGTCCTGCTTCCTAAGACTTAGACTGGGGTTGACAATTGTTTT AGCAACAAGACAATTCAACTATTTCTCCTAGGATTTTTATTATTATTATTTTTTCAC TTTTCTACCAAATGGGTTACATAGGAAGAATGAACTGAAATCTGTCCAGAGCTCCAA GTCCTTTGGAAGAAAGATTAGATGAACGTAAAAATGTTGTTGTTTGCTGTGGCAGTT TACAGCATTTTTCTTGCAAAATTAGTGCAAATCTGTTGGAAATAGAACACAATTCAC AAATTGGAAGTGAACTAAAATGTAATGACGAAAAGGGAGTAGTGTTTTGATTTGGAG GAGGTGTATATTCGGCAGAGGTTGGACTGAGAGTTGGGTGTTATTTAACATAATTAT GGTAATTGGGAAACATTTATAAACACTATTGGGATGGTGATAAAATACAAAAGGGCC TATAGATGTTAGAAATGGGTCAGGTTACTGAAATGGGATTCAATTTGAAAAAAATTT TTTTAAATAGAACTCACTGAACTAGATTCTCCTCTGAGAACCAGAGAAGACCATTTC ATAGTTGGATTCCTGGAGACATGCGCTATCCACCACGTAGCCACTTTCCACATGTGG CCATCAACCACTTAAGATGGGGTTAGTTTAAATCAAGATGTGCTGTTATAATTGGTA TAAGCATAAAATCACACTAGATTCTGGAGATTTAATATGAATAATAAGAATACTATT TCAGTAGTTTTGGTATATTGTGTGTCAAAAATGATAATATTTTGGATGTATTGGGTG AAATAAAATATTAACATTA(SEQIDNO:109) >NP_776160.2T-cellimmunoreceptorwithIgandITIM domainsprecursor[Homosapiens] MRWCLLLIWAQGLRQAPLASGMMTGTIETTGNISAEKGGSIILQCHLSSTTAQVTQV NWEQQDQLLAICNADLGWHISPSFKDRVAPGPGLGLTLQSLTVNDTGEYFCIYHTYP DGTYTGRIFLEVLESSVAEHGARFQIPLLGAMAATLVVICTAVIVVVALTRKKKALR IHSVEGDLRRKSAGQEEWSPSAPSPPGSCVQAEAAPAGLCGEQRGEDCAELHDYFNV LSYRSLGNCSFFTETG(SEQIDNO:110) MouseTIGIT >NM_001146325.1:98-823MusmusculusTcellimmunoreceptor withIgandITIMdomains(Tigit),mRNA ATGCATGGCTGGCTGCTCCTGGTCTGGGTCCAGGGGCTGATACAGGCTGCCTTCCTC GCTACAGGAGCCACAGCAGGCACGATAGATACAAAGAGGAACATCTCTGCAGAGGAA GGTGGCTCTGTCATCTTACAGTGTCACTTCTCCTCTGACACAGCTGAAGTGACCCAA GTCGACTGGAAGCAGCAGGACCAGCTTCTGGCCATTTATAGTGTTGACCTGGGGTGG CATGTCGCTTCAGTCTTCAGTGATCGGGTGGTCCCAGGCCCCAGCCTAGGCCTCACC TTCCAGTCTCTGACAATGAATGACACGGGAGAGTACTTCTGTACCTATCATACGTAT CCTGGTGGGATTTACAAGGGGAGAATATTCCTGAAGGTCCAAGAAAGCTCAGTGGCT CAGTTCCAGACTGCCCCGCTTGGAGGAACCATGGCTGCTGTGCTGGGACTCATTTGC TTAATGGTCACAGGAGTGACTGTACTGGCTAGAAAGAAGTCTATTAGAATGCATTCT ATAGAAAGTGGCCTTGGGAGAACAGAAGCGGAGCCACAGGAATGGAACCTGAGGAGT CTCTCATCCCCTGGAAGCCCTGTCCAGACACAAACTGCCCCTGCTGGTCCCTGTGGA GAGCAGGCAGAAGATGACTATGCTGACCCACAGGAATACTTTAATGTCCTGAGCTAC AGAAGCCTAGAGAGCTTCATTGCTGTATCGAAGACTGGCTAA(SEQIDNO: 111) >NP_001139797.1T-cellimmunoreceptorwithIgandITIM domainsprecursor[Musmusculus] MHGWLLLVWVQGLIQAAFLATGATAGTIDTKRNISAEEGGSVILQCHFSSDTAEVTQ VDWKQQDQLLAIYSVDLGWHVASVFSDRVVPGPSLGLTFQSLTMNDTGEYFCTYHTY PGGIYKGRIFLKVQESSVAQFQTAPLGGTMAAVLGLICLMVTGVTVLARKKSIRMHS IESGLGRTEAEPQEWNLRSLSSPGSPVQTQTAPAGPCGEQAEDDYADPQEYFNVLSY RSLESFIAVSKTG(SEQIDNO:112) Human >NM_001252.5HomosapiensCD70molecule(CD70), CD27L transcriptvariant1,mRNA (CD70) AGAGAGGGGCAGGCTGGTCCCCTGACAGGTTGAAGCAAGTAGACGCCCAGGAGCCCC GGGAGGGGGCTGCAGTTTCCTTCCTTCCTTCTCGGCAGCGCTCCGCGCCCCCATCGC CCCTCCTGCGCTAGCGGAGGTGATCGCCGCGGCGATGCCGGAGGAGGGTTCGGGCTG CTCGGTGCGGCGCAGGCCCTATGGGTGCGTCCTGCGGGCTGCTTTGGTCCCATTGGT CGCGGGCTTGGTGATCTGCCTCGTGGTGTGCATCCAGCGCTTCGCACAGGCTCAGCA GCAGCTGCCGCTCGAGTCACTTGGGTGGGACGTAGCTGAGCTGCAGCTGAATCACAC AGGACCTCAGCAGGACCCCAGGCTATACTGGCAGGGGGGCCCAGCACTGGGCCGCTC CTTCCTGCATGGACCAGAGCTGGACAAGGGGCAGCTACGTATCCATCGTGATGGCAT CTACATGGTACACATCCAGGTGACGCTGGCCATCTGCTCCTCCACGACGGCCTCCAG GCACCACCCCACCACCCTGGCCGTGGGAATCTGCTCTCCCGCCTCCCGTAGCATCAG CCTGCTGCGTCTCAGCTTCCACCAAGGTTGTACCATTGCCTCCCAGCGCCTGACGCC CCTGGCCCGAGGGGACACACTCTGCACCAACCTCACTGGGACACTTTTGCCTTCCCG AAACACTGATGAGACCTTCTTTGGAGTGCAGTGGGTGCGCCCCTGACCACTGCTGCT GATTAGGGTTTTTTAAATTTTATTTTATTTTATTTAAGTTCAAGAGAAAAAGTGTAC ACACAGGGGCCACCCGGGGTTGGGGTGGGAGTGTGGTGGGGGGTAGTGGTGGCAGGA CAAGAGAAGGCATTGAGCTTTTTCTTTCATTTTCCTATTAAAAAATACAAAAATCA (SEQIDNO:113) >NP_001243.1CD70antigenisoform1[Homosapiens] MPEEGSGCSVRRRPYGCVLRAALVPLVAGLVICLVVCIQRFAQAQQQLPLESLGWDV AELQLNHTGPQQDPRLYWQGGPALGRSFLHGPELDKGQLRIHRDGIYMVHIQVTLAI CSSTTASRHHPTTLAVGICSPASRSISLLRLSFHQGCTIASQRLTPLARGDTLCTNL TGTLLPSRNTDETFFGVQWVRP(SEQIDNO:114) MouseCD27L >NM_011617.2MusmusculusCD70antigen(Cd70),mRNA (CD70) GAAGGTGCCAAAAGCTCCAGGGGATTTCCCTGCCCTCCGAGAAGAGGCCCAGTTCTT CCCCTGCATCGGACATCCCCGAGGTTCTAAGGGCAGGTCAAGGCAGGCAGAAGCTTC AAAAGCTCGGCTGAGGAGGCTACAGCTTCCCGCTGCCTTCAGGCCGCTGCTTCCGTG CAGGGATGCCGGAGGAAGGTCGCCCTTGCCCCTGGGTTCGCTGGAGCGGGACCGCGT TCCAGCGCCAATGGCCATGGCTGCTGCTGGTGGTGTTTATTACTGTGTTTTGCTGTT GGTTTCATTGTAGCGGACTACTCAGTAAGCAGCAACAGAGGCTGCTGGAGCACCCTG AGCCGCACACAGCTGAGTTACAGCTGAATCTCACAGTTCCTCGGAAGGACCCCACAC TGCGCTGGGGAGCAGGCCCAGCCTTGGGAAGGTCCTTCACACACGGACCAGAGCTGG AGGAGGGCCATCTGCGTATCCATCAAGATGGCCTCTACAGGCTGCATATCCAGGTGA CACTGGCCAACTGCTCTTCCCCAGGCAGCACCCTGCAGCACAGGGCCACCCTGGCTG TGGGCATCTGCTCCCCCGCTGCGCACGGCATCAGCTTGCTGCGTGGGCGCTTTGGAC AGGACTGTACAGTGGCATTACAGCGCCTGACATACCTGGTCCACGGAGATGTCCTCT GTACCAACCTCACCCTGCCTCTGCTGCCGTCCCGCAACGCTGATGAGACCTTCTTTG GAGTTCAGTGGATATGCCCTTGACCACAACTCCAGGATGACTTGTGAATATTTTTTT TCTTTTCAAGTTCTACGTATTTATAAATGTATATAGTACACATA(SEQIDNO: 115) >NP_035747.1CD70antigen[Musmusculus] MPEEGRPCPWVRWSGTAFQRQWPWLLLVVFITVFCCWFHCSGLLSKQQQRLLEHPEP HTAELQLNLTVPRKDPTLRWGAGPALGRSFTHGPELEEGHLRIHQDGLYRLHIQVTL ANCSSPGSTLQHRATLAVGICSPAAHGISLLRGRFGQDCTVALQRLTYLVHGDVLCT NLTLPLLPSRNADETFFGVQWICP(SEQIDNO:116) Human >NM_001244.4HomosapiensTNFsuperfamilymember8 CD30L (TNFSF8),transcriptvariant1,mRNA (CD153) GTCATTTTCCTACGCGCCCTCTGACATCAGCCACCTTCTCTGTAGCTAGTTTCTCTG CACACAACTTAATCCCTGGCAATGAAAAATGAACCTCTCCCCCACCCTTGCTGCCGC CTCTCGCCTCACGCCCCCAGAGAAGAGTTTCTCCACCAGGCAGCAGGTGAAGGTTTT TTTCCAAGTCACATGATTCAGGATTCAGGGGGAGAATCCTTCTTGGAACAGAGATGG GCCCAGAACTGAATCAGATGAAGAGAGATAAGGTGTGATGTGGGGAAGACTATATAA AGAATGGACCCAGGGCTGCAGCAAGCACTCAACGGAATGGCCCCTCCTGGAGACACA GCCATGCATGTGCCGGCGGGCTCCGTGGCCAGCCACCTGGGGACCACGAGCCGCAGC TATTTCTATTTGACCACAGCCACTCTGGCTCTGTGCCTTGTCTTCACGGTGGCCACT ATTATGGTGTTGGTCGTTCAGAGGACGGACTCCATTCCCAACTCACCTGACAACGTC CCCCTCAAAGGAGGAAATTGCTCAGAAGACCTCTTATGTATCCTGAAAAGGGCTCCA TTCAAGAAGTCATGGGCCTACCTCCAAGTGGCAAAGCATCTAAACAAAACCAAGTTG TCTTGGAACAAAGATGGCATTCTCCATGGAGTCAGATATCAGGATGGGAATCTGGTG ATCCAATTCCCTGGTTTGTACTTCATCATTTGCCAACTGCAGTTTCTTGTACAATGC CCAAATAATTCTGTCGATCTGAAGTTGGAGCTTCTCATCAACAAGCATATCAAAAAA CAGGCCCTGGTGACAGTGTGTGAGTCTGGAATGCAAACGAAACACGTATACCAGAAT CTCTCTCAATTCTTGCTGGATTACCTGCAGGTCAACACCACCATATCAGTCAATGTG GATACATTCCAGTACATAGATACAAGCACCTTTCCTCTTGAGAATGTGTTGTCCATC TTCTTATACAGTAATTCAGACTGAACAGTTTCTCTTGGCCTTCAGGAAGAAAGCGCC TCTCTACCATACAGTATTTCATCCCTCCAAACACTTGGGCAAAAAGAAAACTTTAGA CCAAGACAAACTACACAGGGTATTAAATAGTATACTTCTCCTTCTGTCTCTTGGAAA GATACAGCTCCAGGGTTAAAAAGAGAGTTTTTAGTGAAGTATCTTTCAGATAGCAGG CAGGGAAGCAATGTAGTGTGGTGGGCAGAGCCCCACACAGAATCAGAAGGGATGAAT GGATGTCCCAGCCCAACCTCTAATTCACTGTATGGTCTTGATCTATTTCTTCTGTTT TGAGAGCCTCCAGTTAAAATGGGGCTCCAGTACCAGAGCAGCTAGCAACTCTGCCCT AATGGGAAATGAAGGGGAGCTGGGTGTGAGTGTTTACACTGTGCCCTTCACGGGATA CTTCTTTTATCTGCAGATGGCCTAATACTTAGTTGTCCAAGTCGCGATCAAGGACTC TCTCACACAGGAAACTTCCCTATACTGGCAGATACACTTGTGACTGAACCATGCCCA GTTTATGCCTGTCTGACTGTCACTCTGGCACTAGGAGGCTGATCTTGTACTCCATAT GACCCCACCCCTAGGAACCCCCAGGGAAAACCAGGCTGGGACAGCCCCCTGTTCCTG AGATGGAAAGCACAAATTTAATACACCACCACAATGGAAAACAAGTTCAAAGACTTT TACTTACAGATCCTGGACAGAAAGGGCATAATGAGTCTGAAGGGCAGTCCTCCTTCT CTAGGTTACATGAGGCAGGAATAAGAAGTCAGACAGAGACAGCAAGACAGTTAACAA TGTAGGTAAAGAAATAGGGTGTGGTCACTCTCAATTCACTGGCAAATGCCTGAATGG TCTGTCTGAAGGAAGCAACAGAGAAGTGGGGAATCCAGTCTGCTAGGCAGGAAAGAT GCCTCTAAGTTCTTGTCTCTGGCCAGAGGTGTGGTATAGAACCAGAAACCCATATCA AGGGTGACTAAGCCCGGCTTCTGGTATGAGAAATTAAACTTGTATACAAAATGGTTG CCAAGGCAACATAAAATTATAAGAATTCACTATACCTTCCCCTCCCTGGAACTCAGG ATCCAAGTCTAGAAAATGAAAGGACTGGGTTTGAATTGCTTCAAAACCTCTTCCATC TCAGAAGACCAGACCCTGGGAACTGAGATTCCAGACACAATTTTGGAAGCTCTCCAA CCAAAATAAGGCCCCCCTACCCCAGTATATAATTGAAGACACTAGTAACACCTGACT GCATCTCATCTCAGCAGAGCCAGAATATGGGGACAAGGTTCAGGGTGCCCTGCTGAA TGGTGTGAACAGCAGGATCTCAAGGATGTAATGGAAAGAACTACCACACTGACCATC CAGAATCTAAGAGACCATCTGGGTGTTTGGGAAACCATCTGACGAGGCCTGACTCTA TTCCAGTTAGATTGACAATAATTGAGCAGCAGGCATTTTTCATTTCTGGTCAGGAAA GCATTGTGCCTTTAGCAAACAATCAGTGTGCAACAGTGATGTGGTCATCTAGCCAGG GAATGGCTGCTCCATCCCCTGCATAATATATTCCTGCTTCAAACACCTCTCAGAAAA CCAGTTCCGCGAGGGTTTTTATATCCCCACAAAGTTGTTGAGAGACAATGATGACCC TGGAAGTGGGGAGGAGGACTTCTGAGAAACAGCAACCTCTCTCCTGATTGGGGTAGC CATGAGATTTCTCTAGCTATATCCAACTTGGCATCTGTACATCATCTTTGGAGGAAC ATCTTATTTGTGGAAGGACCTTGACAAGCCGTTTGAGATGGAATGTAGGCCCTGATG TTATGCTTCAGTAAAAAAAGATGGAAGCTTCCCTGCTATACCAAAACATGGAGCAAA ATTTGCATTTTTCTCAAGAAGGAGAGAAAAGGAGTAGGACTCCAGCAAAGTTTGTCA GAAGGAAAGCTAGAAAAGATTTAAAAGAAAAAAAGAAAGAACAAATCAGCAGTGGTG GTATGGATGAAAGGGACTTGAGAGAACAAAAATGGCTAAGGGAAAATTTTAAGTCAT CTGCTGAGCAGTGTGCTGTGTCAACCTCCTCCTAGGTCTCCTCTATGAAATATTTAG TAAAGTCTACATTTCTCTTTAACTCTTTCTGTGAGTAGATTCTTTGGGAGAAGCAGG CATTGGAAGAGGTGTTGAATTCAGCAAGCCAAATGGTCTGTGGTAAAAAACAAAACA GACTTTGAGACTCAAGGCTAAAAAAACAGGGAAATGGCTGGCATTTGAGTCACACAC TAACTGCATAGGACAAATGAATCTTGCTTAAACCAACTCATGCATTCTTGAAAAGGT ATATGCAACCCAACTGTGTGTTAACTAAGCAATTTTTTTGCCATCTCACATTCTAAC TCGAGAAAGATTCCATTTTCATTTTTCACCAACTGTTCTCTGAGCAGAGGTACCTGA CTTTTGCACTGTGAGTGGTTTCTAATCTCAGTCTCTGTCAAGCAATGCTAAGAAAGC CAACACCTAAAGACACAAGGGGTACATCATTTAAATGAATAATGTAACCAAACAAAC AAAAAAAGAGAATAATCATTAATAACTCAACTGATAGATATGTAGGGAGTAGGCAAC CCAGGAAGTTTAAAACTAAATTCTGTTACTCTTGAGGGTTAACCAGCCCCTGGGAAT GTTATGAGCAAATGATACTCCATGAGTAAAATGATATCTATGCAAGTAAAATAAATA ATTTATCTAACTGGGAA(SEQIDNO:117) >NP_001235.1tumornecrosisfactorligandsuperfamily member8isoform1[Homosapiens] MDPGLQQALNGMAPPGDTAMHVPAGSVASHLGTTSRSYFYLTTATLALCLVFTVATI MVLVVQRTDSIPNSPDNVPLKGGNCSEDLLCILKRAPFKKSWAYLQVAKHLNKTKLS WNKDGILHGVRYQDGNLVIQFPGLYFIICQLQFLVQCPNNSVDLKLELLINKHIKKQ ALVTVCESGMQTKHVYQNLSQFLLDYLQVNTTISVNVDTFQYIDTSTEPLENVLSIF LYSNSD(SEQIDNO:118) MouseCD30L >NM_009403.3Musmusculustumornecrosisfactor(ligand) (CD153) superfamily,member8(Tnfsf8),mRNA AGATTAATCCCAGGCGATGAAAAATGAACCTCTCCCCCACCCTTGCAGCCACCCTTC GCCTCACGCCCCCAGAGAAGAGTTTCTCCATCCGGCAACTGGTGAAGGCTTTTTTCC AAGTCACATGATCCAGGATGCAGGGGAAAATCCTTCTTGGAACAGAGCTGGGTACAG AACCGAATCAGATGAGGAGAGATAAGGTGTGATGTGGGACAGACTATATAAAGCATG GAGCCAGGGCTGCAACAAGCAGGCAGCTGTGGGGCTCCTTCCCCTGACCCAGCCATG CAGGTGCAGCCCGGCTCGGTAGCCAGCCCCTGGAGAAGCACGAGGCCCTGGAGAAGC ACAAGTCGCAGCTACTTCTACCTCAGCACCACCGCACTGGTGTGCCTTGTTGTGGCA GTGGCGATCATTCTGGTACTGGTAGTCCAGAAAAAGGACTCCACTCCAAATACAACT GAGAAGGCCCCCCTTAAAGGAGGAAATTGCTCAGAGGATCTCTTCTGTACCCTGAAA AGTACTCCATCCAAGAAGTCATGGGCCTACCTCCAAGTGTCAAAGCATCTCAACAAT ACCAAACTGTCATGGAACGAAGATGGCACCATCCACGGACTCATATACCAGGACGGG AACCTGATAGTCCAATTCCCTGGCTTGTACTTCATCGTTTGCCAACTGCAGTTCCTC GTGCAGTGCTCAAATCATTCTGTGGACCTGACATTGCAGCTCCTCATCAATTCCAAG ATCAAAAAGCAGACGTTGGTAACAGTGTGTGAGTCTGGAGTTCAGAGTAAGAACATC TACCAGAATCTCTCTCAGTTTTTGCTGCATTACTTACAGGTCAACTCTACCATATCA GTCAGGGTGGATAATTTCCAGTATGTGGATACAAACACTTTCCCTCTTGATAATGTG CTATCCGTCTTCTTATATAGTAGCTCAGACTGAATAGTTGTTCTTAACCTTTATGAA AATGCTGTCTACCATACAGTACTTCATCTGTCCAAACATGGGCCAAAGAAAATATTA GGACAACTCAAACTAAGCATGTGAGTTAGTGCACTTCTCTTTCTGTCCTTTGGAAAA ATACAAACCCAGGATTTAGAAAGTGGAGTCTCCTTCAGATGCACAAACAGGAAAGAA TGTGATATGTGCACAGAGACCTACTTGGGCACTAGAAGGGGTTGAGTTGTCCCAGTA TAACCACTAATTCACTGACCTTGAGCCATTTTTCCTTCCCCTGGAACTTGGGGTCTG AATCTGGAAAAGTAGGAGATGAGATTTACATTTCCCCAATATTTTCTTCAACTCAGA AGACGAGACTGTGGAGCTGAGCTCCCTACACAGATGAAGGCCTCCCATGGCATGAGG AAAATGATGGTACCAGTAATGTCTGTCTGACTGTCATCTCAGCAAGTCCTAAGGACT TCCATGCTGCCTTGTTGAAAGATACTCTAACCTCTTGTAATGGGCAAAGTGATCCTG TCTCTCACTGAGGGGAGTAGCTGCTGCCATCTCCTGAGACATACATGGAGACATTTT CTGCCCAAATTCCATTCTGTGTGCAGTTTTTAAGTATTCCCCCAAAAGTTCTTGACA ATGAGAACTTTGAATGTGGGAAGAGCTTCTGGACAGCAAACATTAACAGCTTCTCCT GACCAGAGAGACCATGCAAGCTTGGTCTTAGACCCATCAAGCTTGAGGTTTCTACAT TGTGGGAGACAGACTTTTGACAAACCATTTGAGTTGATGTCTGGGCCCCTGGGAGTT CTCCTTCAGTAAGGAGAGCAAGCCGTTCTAGTGCTGTGTCAGAGGATGGAGTAAAAT AGACACTTTTCTGAAGGAAAGGAGAACAAAGTTCCAGAAAAAGGCTAGAAAATGTTT AAAAGGAAAAGAAAAAACTCAGCTTTTCTCATATGAGAGGAACCCAGAAAAACAACA CTGAAAAAGAAGAGTGGCTCTGTCAACCTCCTCTTAGGTCTCCTCCTCTCTAGTTAT TGGGAAAGGAGTTGCATGGTACAGGACAAGTTCTGGTGTGTGGTCAAATAGAATCAG ATGTGGAGAACACCATGCAGAGAATAAGGAGACCTGTCATATTTGTGTTGTACTCAA ATGAGGGGCAAATGAATCTTAGGCTAAATCAAATAACAGTCTCTGTCAAGCTGTGCT CAGAAAGTCAACCACTGAAGATGGAGGGTGAGGCACGTCATTTAAAAAAAGTGAAAT GTAGC(SEQIDNO:119) >NP_033429.1tumornecrosisfactorligandsuperfamily member8[Musmusculus] MEPGLQQAGSCGAPSPDPAMQVQPGSVASPWRSTRPWRSTSRSYFYLSTTALVCLVV AVAIILVLVVQKKDSTPNTTEKAPLKGGNCSEDLFCTLKSTPSKKSWAYLQVSKHLN NTKLSWNEDGTIHGLIYQDGNLIVQFPGLYFIVCQLQFLVQCSNHSVDLTLQLLINS KIKKQTLVTVCESGVQSKNIYQNLSQFLLHYLQVNSTISVRVDNFQYVDTNTFPLDN VLSVFLYSSSD(SEQIDNO:120) Human >NM_005092.4HomosapiensTNFsuperfamilymember18 GITRL (TNFSF18),mRNA ATCACTTGTGAATTTTTGTTTTCCACAGCTCTCATTTCTCCAAAAATGTGTTTGAGC CACTTGGAAAATATGCCTTTAAGCCATTCAAGAACTCAAGGAGCTCAGAGATCATCC TGGAAGCTGTGGCTCTTTTGCTCAATAGTTATGTTGCTATTTCTTTGCTCCTTCAGT TGGCTAATCTTTATTTTTCTCCAATTAGAGACTGCTAAGGAGCCCTGTATGGCTAAG TTTGGACCATTACCCTCAAAATGGCAAATGGCATCTTCTGAACCTCCTTGCGTGAAT AAGGTGTCTGACTGGAAGCTGGAGATACTTCAGAATGGCTTATATTTAATTTATGGC CAAGTGGCTCCCAATGCAAACTACAATGATGTAGCTCCTTTTGAGGTGCGGCTGTAT AAAAACAAAGACATGATACAAACTCTAACAAACAAATCTAAAATCCAAAATGTAGGA GGGACTTATGAATTGCATGTTGGGGACACCATAGACTTGATATTCAACTCTGAGCAT CAGGTTCTAAAAAATAATACATACTGGGGTATCATTTTACTAGCAAATCCCCAATTC ATCTCCTAGAGACTTGATTTGATCTCCTCATTCCCTTCAGCACATGTAGAGGTGCCA GTGGGTGGATTGGAGGGAGAAGATATTCAATTTCTAGAGTTTGTCTGTCTACAAAAA TCAACACAAACAGAACTCCTCTGCACGTGAATTTTCATCTATCATGCCTATCTGAAA GAGACTCAGGGGAAGAGCCAAAGACTTTTGGTTGGATCTGCAGAGATACTTCATTAA TCCATGATAAAACAAATATGGATGACAGAGGACATGTGCTTTTCAAAGAATCTTTAT CTAATTCTTGAATTCATGAGTGGAAAAATGGAGTTCTATTCCCATGGAAGATTTACC TGGTATGCAAAAAGGATCTGGGGCAGTAGCCTGGCTTTGTTCTCATATTCTTGGGCT GCTGTAATTCATTCTTCTCATACTCCCATCTTCTGAGACCCTCCCAATAAAAAGTAG ACTGATAGGATGGCCACAGATATGCCTACCATACCCTACTTTAGATATGGTGGTGTT AGAAGATAAAGAACAATCTGAGAACTATTGGAATAGAGGTACAAGTGGCATAAAATG GAATGTACGCTATCTGGAAATTTCTCTTGGTTTTATCTTCCTCAGGATGCAGGGTGC TTTAAAAAGCCTTATCAAAGGAGTCATTCCGAACCCTCACGTAGAGCTTTGTGAGAC CTTACTGTTGGTGTGTGTGTCTAAACATTGCTAATTGTAAAGAAAGAGTAACCATTA GTAATCATTAGGTTTAACCCCAGAATGGTATTATCATTACTGGATTATGTCATGTAA TGATTTAGTATTTTTAGCTAGCTTTCCACAGTTTGCAAAGTGCTTTCGTAAAACAGT TAGCAATTCTATGAAGTTAATTGGGCAGGCATTTGGGGGAAAATTTTAGTGATGAGA ATGTGATAGCATAGCATAGCCAACTTTCCTCAACTCATAGGACAAGTGACTACAAGA GGCAATGGGTAGTCCCCTGCATTGCACTGTCTCAGCTTTAGAATTGTTATTTCTGCT ATCGTGTTATAAGACTCTAAAACTTAGCGAATTCACTTTTCAGGAAGCATATTCCCC TTTAGCCCAAGGTGAGCAGAGTGAAGCTACAACAGATCTTTCCTTTACCAGCACACT TTTTTTTTTTTTCCTGCCTGAATCAGGGAGATCCAGGATGCTGTTCAGGCCTTATCC CAACCAAATTCCCCTCTTCACTTTGCAGGGCCCATCTTAGTCAAATGTGCTAACTTC TAAAATAATAAATAGCACTAATTCAAAATTTTTGGACTCTTAAATTAGCTACTTGCA GGTTCTTGTTGAAAGGTATATAATATTACATTGTAAACAAATTTAAAATATTTATGG ATATTTGTGAAAAGCTGCATTATGTTAAATAATATTACATGTAAAGCTATTTAAAAG AGGTTTTTTTTGTATTTTGTTTAACAAAAATTGCTCAGGAGCATGCTAAGCCTGAGG CCAAGTTGTTTCTTAGTATGACTTTTTAAAAAAACATCTGCTGAGTAGCTACAGGGC CAAAGACTTGGAGAGCTTGTTTCTGTTGCATTTGCATATCTTCTCAGGAAATTAAAG TGTGTCATACATATGTGTGTGTGTGTGTGTGTGTGTGTGTATATGTGTGTGTGTATA TATATGTATACTTATAAAATCTTGGTGTTCTTGATCTTTGTTGTGTTATAAGCAATG TGTGCTGGAGTGGGCTGGTGCTAGCTTATAAGCACATATTATTAAATTTTCAGGAAT GTTGCACTTTAGTTATTAACTATAGGCATTCTTGAAATTGGCTATGGTGGGAGTATT TATACCATGTAAATTGGCAAACACTACACATTTTCCTTTTGGACAGCTAGTTCACCA GCACACCACTGTGAAACTCTCCTTAATGACTCCTCTCTGCCCCCGCTTCATTCCTGG GATAATCATAGCAGACTAAGGGAGAAAATGAAATTGTAAAAATTTGGCATACTGGTG ATTTCTCAGGGCAAGCAGAGGTTACTACAGCTGCAGCTAGAGGGATGACTACCAACA GGTGACCTTTACATTTTCCTGATGTTATAATTTTAGCTTTTGTTTTCAATGTATACT GTTTTCCTGTTTCTCCACATAGTAGTCTGCATTTTAAATCTATAATAAAACATGCTG ATAACTGG(SEQIDNO:121) >NP_005083.3tumornecrosisfactorligandsuperfamily member18[Homosapiens] MCLSHLENMPLSHSRTQGAQRSSWKLWLFCSIVMLLELCSESWLIFIFLQLETAKEP CMAKFGPLPSKWQMASSEPPCVNKVSDWKLEILQNGLYLIYGQVAPNANYNDVAPFE VRLYKNKDMIQTLTNKSKIQNVGGTYELHVGDTIDLIFNSEHQVLKNNTYWGIILLA NPQFIS(SEQIDNO:122) MouseGITRL >NM_183391.3Musmusculustumornecrosisfactor(ligand) superfamily,member18(Tnfsf18),mRNA TTGTGGGTATCTGCTTTCCCCAGTTCTCATTCCATCAGAGAACGAGTTCTAGCCTCA TGGAGGAAATGCCTTTGAGAGAATCAAGTCCTCAAAGGGCAGAGAGGTGCAAGAAGT CATGGCTCTTGTGCATAGTGGCTCTGTTACTGATGTTGCTCTGTTCTTTGGGTACAC TGATCTATACTTCACTCAAGCCAACTGCCATCGAGTCCTGCATGGTTAAGTTTGAAC TATCATCCTCAAAATGGCACATGACATCTCCCAAACCTCACTGTGTGAATACGACAT CTGATGGGAAGCTGAAGATACTGCAGAGTGGCACATATTTAATCTACGGCCAAGTGA TTCCTGTGGATAAGAAATACATAAAAGACAATGCCCCCTTCGTAGTACAGATATATA AAAAGAATGATGTCCTACAAACTCTAATGAATGATTTTCAAATCTTGCCTATAGGAG GGGTTTATGAACTGCATGCTGGAGATAACATATATCTGAAGTTCAACTCTAAAGACC ATATTCAGAAAACTAACACATACTGGGGGATCATCTTAATGCCTGATCTACCATTCA TCTCTTAGAGATTGGGTTTGGTCTCCTCATCTTCTTCTTTGTATCCCGAGATGCTGG TGGGTGGGTTGGAGGGGGATGATTGATGGCAATGCACACAGTTTGTGAGGGCTTACA AATTGACACAATCAGAGCCTCTTGGCATATAAAATTTTAGCCCTCATATCTGTCTGA AGAGGACTCAGCAAATGGGCCAATCCCTAATGTTGGGTCTGCAAATGGACTTGTACA ATCCATGATAAAAAGGAGTATGGGCCACAGAAGACAGAAACTCTTCCAAAGAATGTC TTTCTAACCTTGATCCCTGGGTAGAATGAGATCCTGTTTCCATGGGAGTCTTACTTG GCTTGCAAAAAAGGGTGTAGGGCAGTAGCTTGGCCTTTTTTCCATCATAATTTCCTT GAGCTGTTTTACCTTAATCCCTCCAAACTCTCACCTTCTGAGAGCCTCCTAATGAAA CATTGTTAGACTGGTGGGGTGGCCAAGACATGCCAACAACACCCTTCTTTAGAGGTG GTGTTTTTAGAGGACAGAGAACATTATGAAGCCTAGAGCAGCAGAGGTCAAGATGCC ACGAAATGGAATTGATCTGGGAATTTTTTTTTTTTTTCATTCTCAGGATGCAGGTTC ATTCTGAACTTTCCCCTAGGCCTTCATTGCTTTTGTGTGTATGTGTGCATAAATTCT GCAAATAGAAAAATGAGAGTTTGCACCAGTACTCACTAGATTTAACACCAGAAAGTG GTACTTTTCTGGCTGTATTATGCCATGATAGCACATTTTCTGTTGGTGTTCCCTAAC TGACAAGTATAACAGTTTTCCTAAACCACACAACAATGCTATGATGTTAATGGGGTA GATATTTTTGGAAAAAAATTGCACAGTGAGAACATGGGTAGATGAACCCTAAGACTC TTACCTCAATTCAGAACTCGCAAGGAGTTAAGTGAGTGGGGTCTTCATTAGACCATT CACATGGTCTCTGCTTTGAAACTGGCGTTGCTACTGTCTCATTATACATCACTAAAA TGGAATTAACTCAACTTTGAAATGGATGCATCGACTTTACCCCAAGGTGTCCAGAAT GAAGCTACAAGACTTTTACCAGCAGTCATTTTCCTTTTGCCTGGAGCAAGAAGATCC AGGATACTGTTGGAAGAGTTCATCTCACTCAACCATGCTGACTTTCCAAAGTAATAA TGAACATTTGTGTTCAAATTTTGGATTCTGTTAAATTTAGCCAGCTTGTGAGTTCTT GTCGAAAAGTATTTTAAACCAATTTACACTATTTATGGGTATTTGTGAAAAGCTATA TAGTGATATTTTATATATAACTAATTTAAAATATTTTTATTTTATGTAACAAAAATA CTATAGGCTAAGCTATTTCTTCTTATTTTTTTATGAATACTTGCTGAATTGCCATAG GGCACAAAGACTCTTCTGTTTGCATATCTTCTCAGGAAATTAAAATTGTATCACATG TATTTATAAGAA(SEQIDNO:123) >NP_899247.3tumornecrosisfactorligandsuperfamily member18[Musmusculus] MEEMPLRESSPQRAERCKKSWLLCIVALLLMLLCSLGTLIYTSLKPTAIESCMVKFE LSSSKWHMTSPKPHCVNTTSDGKLKILQSGTYLIYGQVIPVDKKYIKDNAPFVVQIY KKNDVLQTLMNDFQILPIGGVYELHAGDNIYLKENSKDHIQKTNTYWGIILMPDLPF IS(SEQIDNO:124) Human >NM_000074.3HomosapiensCD40ligand(CD40LG),mRNA CD40L AATCCTGAGTAAGGTGGCCACTTTGACAGTCTTCTCATGCTGCCTCTGCCACCTTCT (CD154) CTGCCAGAAGATACCATTTCAACTTTAACACAGCATGATCGAAACATACAACCAAAC TTCTCCCCGATCTGCGGCCACTGGACTGCCCATCAGCATGAAAATTTTTATGTATTT ACTTACTGTTTTTCTTATCACCCAGATGATTGGGTCAGCACTTTTTGCTGTGTATCT TCATAGAAGGTTGGACAAGATAGAAGATGAAAGGAATCTTCATGAAGATTTTGTATT CATGAAAACGATACAGAGATGCAACACAGGAGAAAGATCCTTATCCTTACTGAACTG TGAGGAGATTAAAAGCCAGTTTGAAGGCTTTGTGAAGGATATAATGTTAAACAAAGA GGAGACGAAGAAAGAAAACAGCTTTGAAATGCAAAAAGGTGATCAGAATCCTCAAAT TGCGGCACATGTCATAAGTGAGGCCAGCAGTAAAACAACATCTGTGTTACAGTGGGC TGAAAAAGGATACTACACCATGAGCAACAACTTGGTAACCCTGGAAAATGGGAAACA GCTGACCGTTAAAAGACAAGGACTCTATTATATCTATGCCCAAGTCACCTTCTGTTC CAATCGGGAAGCTTCGAGTCAAGCTCCATTTATAGCCAGCCTCTGCCTAAAGTCCCC CGGTAGATTCGAGAGAATCTTACTCAGAGCTGCAAATACCCACAGTTCCGCCAAACC TTGCGGGCAACAATCCATTCACTTGGGAGGAGTATTTGAATTGCAACCAGGTGCTTC GGTGTTTGTCAATGTGACTGATCCAAGCCAAGTGAGCCATGGCACTGGCTTCACGTC CTTTGGCTTACTCAAACTCTGAACAGTGTCACCTTGCAGGCTGTGGTGGAGCTGACG CTGGGAGTCTTCATAATACAGCACAGCGGTTAAGCCCACCCCCTGTTAACTGCCTAT TTATAACCCTAGGATCCTCCTTATGGAGAACTATTTATTATACACTCCAAGGCATGT AGAACTGTAATAAGTGAATTACAGGTCACATGAAACCAAAACGGGCCCTGCTCCATA AGAGCTTATATATCTGAAGCAGCAACCCCACTGATGCAGACATCCAGAGAGTCCTAT GAAAAGACAAGGCCATTATGCACAGGTTGAATTCTGAGTAAACAGCAGATAACTTGC CAAGTTCAGTTTTGTTTCTTTGCGTGCAGTGTCTTTCCATGGATAATGCATTTGATT TATCAGTGAAGATGCAGAAGGGAAATGGGGAGCCTCAGCTCACATTCAGTTATGGTT GACTCTGGGTTCCTATGGCCTTGTTGGAGGGGGCCAGGCTCTAGAACGTCTAACACA GTGGAGAACCGAAACCCCCCCCCCCCCCCCGCCACCCTCTCGGACAGTTATTCATTC TCTTTCAATCTCTCTCTCTCCATCTCTCTCTTTCAGTCTCTCTCTCTCAACCTCTTT CTTCCAATCTCTCTTTCTCAATCTCTCTGTTTCCCTTTGTCAGTCTCTTCCCTCCCC CAGTCTCTCTTCTCAATCCCCCTTTCTAACACACACACACACACACACACACACACA CACACACACACACACACACACACAGAGTCAGGCCGTTGCTAGTCAGTTCTCTTCTTT CCACCCTGTCCCTATCTCTACCACTATAGATGAGGGTGAGGAGTAGGGAGTGCAGCC CTGAGCCTGCCCACTCCTCATTACGAAATGACTGTATTTAAAGGAAATCTATTGTAT CTACCTGCAGTCTCCATTGTTTCCAGAGTGAACTTGTAATTATCTTGTTATTTATTT TTTGAATAATAAAGACCTCTTAACATTA(SEQIDNO:125) >NP_000065.1CD40ligand[Homosapiens] MIETYNQTSPRSAATGLPISMKIFMYLLTVFLITQMIGSALFAVYLHRRLDKIEDER NLHEDFVFMKTIQRCNTGERSLSLLNCEEIKSQFEGFVKDIMLNKEETKKENSFEMQ KGDQNPQIAAHVISEASSKTTSVLQWAEKGYYTMSNNLVTLENGKQLTVKRQGLYYI YAQVTFCSNREASSQAPFIASLCLKSPGRFERILLRAANTHSSAKPCGQQSIHLGGV FELQPGASVFVNVTDPSQVSHGTGFTSFGLLKL(SEQIDNO:126) MouseCD40L >NM_011616.2MusmusculusCD40ligand(Cd401g),mRNA CTTTCAGTCAGCATGATAGAAACATACAGCCAACCTTCCCCCAGATCCGTGGCAACT GGACTTCCAGCGAGCATGAAGATTTTTATGTATTTACTTACTGTTTTCCTTATCACC CAAATGATTGGATCTGTGCTTTTTGCTGTGTATCTTCATAGAAGATTGGATAAGGTC GAAGAGGAAGTAAACCTTCATGAAGATTTTGTATTCATAAAAAAGCTAAAGAGATGC AACAAAGGAGAAGGATCTTTATCCTTGCTGAACTGTGAGGAGATGAGAAGGCAATTT GAAGACCTTGTCAAGGATATAACGTTAAACAAAGAAGAGAAAAAAGAAAACAGCTTT GAAATGCAAAGAGGTGATGAGGATCCTCAAATTGCAGCACACGTTGTAAGCGAAGCC AACAGTAATGCAGCATCCGTTCTACAGTGGGCCAAGAAAGGATATTATACCATGAAA AGCAACTTGGTAATGCTTGAAAATGGGAAACAGCTGACGGTTAAAAGAGAAGGACTC TATTATGTCTACACTCAAGTCACCTTCTGCTCTAATCGGGAGCCTTCGAGTCAACGC CCATTCATCGTCGGCCTCTGGCTGAAGCCCAGCAGTGGATCTGAGAGAATCTTACTC AAGGCGGCAAATACCCACAGTTCCTCCCAGCTTTGCGAGCAGCAGTCTGTTCACTTG GGCGGAGTGTTTGAATTACAAGCTGGTGCTTCTGTGTTTGTCAACGTGACTGAAGCA AGCCAAGTGATCCACAGAGTTGGCTTCTCATCTTTTGGCTTACTCAAACTCTGAACA GTGCGCTGTCCTAGGCTGCAGCAGGGCTGATGCTGGCAGTCTTCCCTATACAGCAAG TCAGTTAGGACCTGCCCTGTGTTGAACTGCCTATTTATAACCCTAGGATCCTCCTCA TGGAGAACTATTTATTATGTACCCCCAAGGCACATAGAGCTGGAATAAGAGAATTAC AGGGCAGGCAAAAATCCCAAGGGACCCTGCTCCCTAAGAACTTACAATCTGAAACAG CAACCCCACTGATTCAGACAACCAGAAAAGACAAAGCCATAATACACAGATGACAGA GCTCTGATGAAACAACAGATAACTAATGAGCACAGTTTTGTTGTTTTATGGGTGTGT CGTTCAATGGACAGTGTACTTGACTTACCAGGGAAGATGCAGAAGGGCAACTGTGAG CCTCAGCTCACAATCTGTTATGGTTGACCTGGGCTCCCTGCGGCCCTAGTAGG (SEQIDNO:127) >NP_035746.2CD40ligand[Musmusculus] MIETYSQPSPRSVATGLPASMKIFMYLLTVFLITQMIGSVLFAVYLHRRLDKVEEEV NLHEDFVFIKKLKRCNKGEGSLSLLNCEEMRRQFEDLVKDITLNKEEKKENSFEMQR GDEDPQIAAHVVSEANSNAASVLQWAKKGYYTMKSNLVMLENGKQLTVKREGLYYVY TQVTFCSNREPSSQRPFIVGLWLKPSSGSERILLKAANTHSSSQLCEQQSVHLGGVF ELQAGASVFVNVTEASQVIHRVGFSSFGLLKL(SEQIDNO:128) Human >NM_003807.5HomosapiensTNFsuperfamilymember14 LIGHT (TNFSF14),transcriptvariant1,mRNA (CD258) CGAGACTCCATCTCAAAAACAAAACAAATAAACGAACAAAAAAACCCACAACGTATT ATTTTCTTGTTTACGAGGTTTCTTGTCTCTCTGGCTCCACCAGAAGAGGAGCAGGGA CCCTTCTTGCTGTTGTTCATTGCTGCATCCCCCACACCGAGAGCAGAGCCTGGCATG GGCAGAAAGTCCTCAGTCGATATTTGGTGGCCCCAAGCGAATGAAGCATCCAAGAAG GGAAAGCTGGGGGCTCCCCACTGCACTTGCCACCTGAGTCACATTTTCAGAAGCCTC TGGAAAGTCGTGCACAGCCCAGGAGTGTTGAGCAATTTCGGTTTCCTCTGAGGTTGA AGGACCCAGGCGTGTCAGCCCTGCTCCAGACACCTTGGGCATGGAGGAGAGTGTCGT ACGGCCCTCAGTGTTTGTGGTGGATGGACAGACCGACATCCCATTCACGAGGCTGGG ACGAAGCCACCGGAGACAGTCGTGCAGTGTGGCCCGGGTGGGTCTGGGTCTCTTGCT GTTGCTGATGGGGGCCGGGCTGGCCGTCCAAGGCTGGTTCCTCCTGCAGCTGCACTG GCGTCTAGGAGAGATGGTCACCCGCCTGCCTGACGGACCTGCAGGCTCCTGGGAGCA GCTGATACAAGAGCGAAGGTCTCACGAGGTCAACCCAGCAGCGCATCTCACAGGGGC CAACTCCAGCTTGACCGGCAGCGGGGGGCCGCTGTTATGGGAGACTCAGCTGGGCCT GGCCTTCCTGAGGGGCCTCAGCTACCACGATGGGGCCCTTGTGGTCACCAAAGCTGG CTACTACTACATCTACTCCAAGGTGCAGCTGGGCGGTGTGGGCTGCCCGCTGGGCCT GGCCAGCACCATCACCCACGGCCTCTACAAGCGCACACCCCGCTACCCCGAGGAGCT GGAGCTGTTGGTCAGCCAGCAGTCACCCTGCGGACGGGCCACCAGCAGCTCCCGGGT CTGGTGGGACAGCAGCTTCCTGGGTGGTGTGGTACACCTGGAGGCTGGGGAGAAGGT GGTCGTCCGTGTGCTGGATGAACGCCTGGTTCGACTGCGTGATGGTACCCGGTCTTA CTTCGGGGCTTTCATGGTGTGAAGGAAGGAGCGTGGTGCATTGGACATGGGTCTGAC ACGTGGAGAACTCAGAGGGTGCCTCAGGGGAAAGAAAACTCACGAAGCAGAGGCTGG GCGTGGTGGCTCTCGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCAGGCGGATCA CCTGAGGTCAGGAGTTCGAGACCAGCCTGGCTAACATGGCAAAACCCCATCTCTACT AAAAATACAAAAATTAGCCGGACGTGGTGGTGCCTGCCTGTAATCCAGCTACTCAGG AGGCTGAGGCAGGATAATTTTGCTTAAACCCGGGAGGCGGAGGTTGCAGTGAGCCGA GATCACACCACTGCACTCCAACCTGGGAAACGCAGTGAGACTGTGCCTCAAAAAAAA GAAAGGAAGAAAAAAGAAAACTCAGGAAACAGATCTTGGGGGACACTCCAGGGAACC CAAAACTCAAAGGCGGAGAGCTCAGTGGGCACCACCAAGGCGAGATGAAGCCCCAGC AGGCACCTTCAGAAGACCCACGTAGACTGCAGACCCTGCCACGGACAATACTAAGGA CAAAAACCCAGAGACTTGGGGTCTGTGGGCCCCCAAACATGGGGTAAAGTTGATTTG CCTGATATTCAGGAAGAAGGGGTGAGGGGTGGGTATTTATGCTTTTGATTCAGAAGA AAGTGGGGCTTGGGATTCCAGGGACTTGGCTGGGGGTGGGAAACTTCATCCACTTCC CTACTCTCATCATGAGTACGGACAGGGTGGGCGGGAGACTGATCATCGGGACTCATC ATGAAGAGCCCAGCCCCACCCCACATACTCAGATCCCACCCACAGACTGGTGGCCAC ACCTCAGCCTGGTCACAAAGAGTTACACTCAGATACATGAGCACGGCAGCGTGCTCA TAACTGTTTAACAACCAGCTGTCCTGGGAGGGGGACAGCTTTGTAATGTTTGCCAAT TTCCATGGTGTAAATGCTACCACCATGGCTGATTTCATCACTGCCAAGCATAGACAT CCCTAATAGGACACCACGGATCTGTCCCCGGCATCCGGCCCAGGGCCTGGCACAAAG CATGCTCTAGGGAAATGCTTGCTGATTGAAAGGAAGGAAGAATGACTCTACAGTCAC ACCTATGGCATCCCACAAAATCTGTCACATGGCTGCATAATCTCAGCCACTCTTTCA CAACTATAGACTCATACACGCGAAGTGCCAGATTCATGCACAACCACACAATCACAT GGAAGTCACAGACGGCATCACAGACAGTCACAGCACTGTGTGTATGTTATAACACAA GCACACAAAACTCAGACAGCATCCCAGCTACACAGCCACTCCCAGAGGTGTCACCGT CACACTTGGTAATTAATACTCATTACATTAGACACAGACAGACCAAGTTATAGTCAG ACCTGGTTACACACATACACACACACAATATCACCATGACAAATACACATTACACAC ACACAACATCACAATGACAAACACACATTACACACACAACATCACGATGACAAACAC ACATTACACACACAACATCACGATGACAAACACACATTACACACACATCACAATGAC AAACACAACATTACACACACACAACATCACAATGACACACACATCACACACACATCA CAATGACAAACACACAACATTACACACATATACACACAGCCTGAGGGCCCTCCCCAG CCCAGACTAACACATCTCGGGGTGAGGACCAGACCTTGTTCATAACCCTGGGCCTCT TAACCACTGATCTTTGAAATAAATGGCAAATAGTTGTACCTGGATCTGTCTAGTTCT TAGGGGAACAAACTGAAGAAGGGTGGAGAGGAATTGTCAGGCCTAAAGAGCCCCACA GGGAAAGGGAGGAGTCGGATGGGGGGCAACCATCAGCAACAAGTGGTGGCTCCTAGA GGCAGAGGGATGGAGGTAATGACCCATGGAGGTCATTCTACAGATGAGGAACCTGGA CCCAGTTGGCTCAAGTCCATGCAGGAAATGTGGGGGAAACCAGAGACCTCACGTCTG GATCTGGCTTCCTCTCCAATCCACAATTCCTGAGGAAGTAGAGGCTACATCCCGCAA GACGCCCTTATTAGACACATCCAGGACAGAATGACAATCCGCCAAGCCAGCTGGAAG CATAAAACACAGGGAGCTGGTGGGTTGGGTGGGGGCAGATAATGATATGCATACAAA TTAGAGGGTCTATGCAAATGAGCATTGCTGCAGTGTGGCTGGAGGGAATCCTTAGTT CCTAGGATTCTAGGATATGGGTTTCGACCCCAGAGGTGAATGTATTGTTATTATTGT TTTGTTGTTGTTGTGAATGACAAGTCAAAATTTGTGGGTTATTGTTGTTATCGCCAA TAGTATTCTTGTCATTGTTGCACAGTACAGAGATGAAGGAAACAGATTTTGCAATCA GATGATCCTGGGTTCTGAGTCCACTCTGCCACTCACCAGCTATATGACCTCCAGCAA TTTCCATCACCTCTCAATGCTTCAGTTTCCCCATCGGCAAGATGGTTGTGGGGGGAG AGGAACAACAGTACAGATTCACCATCCCAAATTCAAAATGCTCCAAAATCTAGGCCG GGCGTGGTGGCTCATACCTGTAATCCCAGCACTTTGGGAGGTCAAAGTGGACGGATA ACCTGAGGTCAGGAGCTCCAGACCAGCCTGGCCAACATGGCGAAACCCCATCTCTAC TAAAAATACAAAAAATTACCTGGGTGTGGTGGGGGGCACCTGTAACCCCAGCTACTC GGGAGGCTGAGGCAGGAACCCTGGAGGTTGAGGTTGCAGTGAGCTGAGATCACACCA CTGCACTCCAGCCTGGGTGACAGAGCAAGGCTCCCATCTCAAAAAACAAAAAAACAT GCTCCAAAATCTGAAACTCTTTGAGCCCCAGTGTGATGCCACAAGTGGGAAATTCCA CAACTCATCACATGTGATAGATTGCAGTGGAAATGCAGGCACACACCACGAAGTTTA CTCAGCATCCTCAAAGGAAATCCCCGTCAGTAGCTATATATCATTTTCTCACATGCC AGATAGGTATCTCTCATCTTTTACTGTTAGGTACTTCTGTGTTGAATAGGTGGAGGA AAATGATTGCTGGTTAGTAGTATATAAATTCAGAGTCAGGAAGGATGGTGATGTCGG CTGGGTGCAGTGGCTCATGCCTGTAATTCCAATGTGATACCCTACCTTGTGTTTAAC GTGATTGACTCTCCCTTAGCTGAGAGGGCCAGGCAGACTCTATTTTGGCTTCTTCGC TTGCAGTCTCTCACCCACCCCCCTTCCTCAAGGACTTAAGCTGACTCCCAGCACATC CAAGAATGCGATTACTGATAAGATACTGTGACAAGCTATATCCACAATTCCCAGGAA TTCGTCCGGTTGATAGCACCCAAAGCCCCCGCGTCTATCACCTTGTGATAGATTTAA AGCCCCTGCACCTGGAACTGTTTGTTTTTCTGTTACCATTTATCTTTTTCACTTTCT TGCCTGTTTTGCTTCTGTAAAATTGCTTCAGCTCGGCTCCCTCTTCCCCTTCTAAAC CAAGGTATAAAAAGAAACCTAGCCCCTTCTTTGGGGTGGAGAGAATTTTGAGCGCTA GCCGTCTCTCAGTCGCCGGCTAATAAAGGACTCCTGAATTAGTCTAA(SEQID NO:129) >NP_003798.2tumornecrosisfactorligandsuperfamily member14isoform1[Homosapiens] MEESVVRPSVFVVDGQTDIPFTRLGRSHRRQSCSVARVGLGLLLLLMGAGLAVQGWF LLQLHWRLGEMVTRLPDGPAGSWEQLIQERRSHEVNPAAHLTGANSSLTGSGGPLLW ETQLGLAFLRGLSYHDGALVVTKAGYYYIYSKVQLGGVGCPLGLASTITHGLYKRTP RYPEELELLVSQQSPCGRATSSSRVWWDSSFLGGVVHLEAGEKVVVRVLDERLVRLR DGTRSYFGAFMV(SEQIDNO:130) MouseLIGHT >NM_019418.3Musmusculustumornecrosisfactor(ligand) superfamily,member14(Tnfsf14),mRNA TTTTGCAGTTTGCACAGCCCGAGCGTGTTGGGCAATTGTGGTTTCCTCCGGAGAGGA GGAACTCAGGCTTGCCAACCCTTTCCCTGGGCTTCGGAGCCTCAGCTGCTCTGGCAT GGAGAGTGTGGTACAGCCTTCAGTGTTTGTGGTGGATGGACAGACGGACATCCCATT CAGGCGGCTGGAACAGAACCACCGGAGACGGCGCTGTGGCACTGTCCAGGTCAGCCT GGCCCTGGTGCTGCTGCTAGGTGCTGGGCTGGCCACTCAGGGCTGGTTTCTCCTGAG ACTGCATCAACGTCTTGGAGACATAGTAGCTCATCTGCCAGATGGAGGCAAAGGCTC CTGGGAGAAGCTGATACAAGATCAACGATCTCACCAGGCCAACCCAGCAGCACATCT TACAGGAGCCAACGCCAGCTTGATAGGTATTGGTGGACCTCTGTTATGGGAGACACG ACTTGGCCTGGCCTTCTTGAGGGGCTTGACGTATCATGATGGGGCCCTGGTGACCAT GGAGCCCGGTTACTACTATGTGTACTCCAAAGTGCAGCTGAGCGGCGTGGGCTGCCC CCAGGGGCTGGCCAATGGCCTCCCCATCACCCATGGACTATACAAGCGCACATCCCG CTACCCGAAGGAGTTAGAACTGCTGGTCAGTCGGCGGTCACCCTGTGGCCGGGCCAA CAGCTCCCGAGTCTGGTGGGACAGCAGCTTCCTGGGCGGCGTGGTACATCTGGAGGC TGGGGAAGAGGTGGTGGTCCGCGTGCCTGGAAACCGCCTGGTCAGACCACGTGACGG CACCAGGTCCTATTTCGGAGCTTTCATGGTCTGAAGGCTGCGGTGACAATGTATTTT GTGGAGGGACCTCTCCAGGACTCACCTCAAACCCAGCAATAGGGTTTGAAGTCCTCC CTTTAAGGAGCCCTGAACTCTGCAGTGCTCGGGGCGGTGTAGACTGCTGACCTGCTT TGGGCAATCTTCAAATCAGAGACCTGGAGACTTGGGGCGTGGAGCCCAGGAGCGAGG GGTCAGCTCATTTGCCTGATATTCAGGAAGAAAGAATCAAGCTGGGGTATTTATGCT TCTGATGCAAACACTGAGATTTCGGCTTTCTGGGTTTTGAGCTGGAGGCAAGAAACC TTCCCAGAGTGTCATCAGGACCATGTTGGCAGGACTTGGGGCTCCAGACTTGCCACC ACACTCTGGCCTCTCCCATCCATCCGCTGCATTGGTTTCCAGCCACCAAAACAGCAC TGGCCCCCTGGCTGCAACTGGCCAGGTACGAGCTTCTGAGCACCTACATTCCTCAGG GACATCTTGATGAGATCTCAGTACTCAGTCCAATGCGCAGCAGCGACAGACATGCCA GGAATGGTTGGTCAGAAGGGAAGGGAGGAAAGGGAGGAAAGAAGGGAATGCAGAAGA GAAGGGGGGAAAACAAGACCAAAACAAAACAGCAACAACAAAGCGGCAGGGAGGAGG TGACACCCTTGGGGATACTTTAGTCAACACACTTAGAACAGATTGTGCCAGGCCTGT TGGATTCCTGGAGTTGATGGGATCGTGGGAAGGCACAATGGGGAGCAAGTGGGCTTG GGTTATGGCTCAGTGGGTAAAGTGCAATTATGGGGATCTGAGTTTGAATCCCTGGTA CCCATATAAAGACACAGATGCGGTGATGGGCACTTGTGACAATGAGATCATCAATAG GGAATGGAGACAGGAGGGACCTCTGGGGTTCACTGGCCAGGCAGTCTAGCTGAATCA AAGAGCTCCAAGTTCAGTCGATAGCTCCTGAAGATGACAACTGAGGCTATTCTCCAA ACCCCACACGCAGGACACATGCGTAATAAATAAAATTTTAAAAAT(SEQIDNO: 131) >NP_062291.1tumornecrosisfactorligandsuperfamily member14[Musmusculus] MESVVQPSVFVVDGQTDIPFRRLEQNHRRRRCGTVQVSLALVLLLGAGLATQGWFLL RLHQRLGDIVAHLPDGGKGSWEKLIQDQRSHQANPAAHLTGANASLIGIGGPLLWET RLGLAFLRGLTYHDGALVTMEPGYYYVYSKVQLSGVGCPQGLANGLPITHGLYKRTS RYPKELELLVSRRSPCGRANSSRVWWDSSFLGGVVHLEAGEEVVVRVPGNRLVRPRD GTRSYFGAFMV(SEQIDNO:132) HumanTL1 >NM_005118.4HomosapiensTNFsuperfamilymember15 (TNFSF15),transcriptvariant1,mRNA AGAGGTGCCTCCAGGAGCAGCAGGAGCATGGCCGAGGATCTGGGACTGAGCTTTGGG GAAACAGCCAGTGTGGAAATGCTGCCAGAGCACGGCAGCTGCAGGCCCAAGGCCAGG AGCAGCAGCGCACGCTGGGCTCTCACCTGCTGCCTGGTGTTGCTCCCCTTCCTTGCA GGACTCACCACATACCTGCTTGTCAGCCAGCTCCGGGCCCAGGGAGAGGCCTGTGTG CAGTTCCAGGCTCTAAAAGGACAGGAGTTTGCACCTTCACATCAGCAAGTTTATGCA CCTCTTAGAGCAGACGGAGATAAGCCAAGGGCACACCTGACAGTTGTGAGACAAACT CCCACACAGCACTTTAAAAATCAGTTCCCAGCTCTGCACTGGGAACATGAACTAGGC CTGGCCTTCACCAAGAACCGAATGAACTATACCAACAAATTCCTGCTGATCCCAGAG TCGGGAGACTACTTCATTTACTCCCAGGTCACATTCCGTGGGATGACCTCTGAGTGC AGTGAAATCAGACAAGCAGGCCGACCAAACAAGCCAGACTCCATCACTGTGGTCATC ACCAAGGTAACAGACAGCTACCCTGAGCCAACCCAGCTCCTCATGGGGACCAAGTCT GTATGCGAAGTAGGTAGCAACTGGTTCCAGCCCATCTACCTCGGAGCCATGTTCTCC TTGCAAGAAGGGGACAAGCTAATGGTGAACGTCAGTGACATCTCTTTGGTGGATTAC ACAAAAGAAGATAAAACCTTCTTTGGAGCCTTCTTACTATAGGAGGAGAGCAAATAT CATTATATGAAAGTCCTCTGCCACCGAGTTCCTAATTTTCTTTGTTCAAATGTAATT ATAACCAGGGGTTTTCTTGGGGCCGGGAGTAGGGGGCATTCCACAGGGACAACGGTT TAGCTATGAAATTTGGGGCCCAAAATTTCACACTTCATGTGCCTTACTGATGAGAGT ACTAACTGGAAAAAGGCTGAAGAGAGCAAATATATTATTAAGATGGGTTGGAGGATT GGCGAGTTTCTAAATATTAAGACACTGATCACTAAATGAATGGATGATCTACTCGGG TCAGGATTGAAAGAGAAATATTTCAACACCTTCCTGCTATACAATGGTCACCAGTGG TCCAGTTATTGTTCAATTTGATCATAAATTTGCTTCAATTCAGGAGCTTTGAAGGAA GTCCAAGGAAAGCTCTAGAAAACAGTATAAACTTTCAGAGGCAAAATCCTTCACCAA TTTTTCCACATACTTTCATGCCTTGCCTAAAAAAAATGAAAAGAGAGTTGGTATGTC TCATGAATGTTCACACAGAAGGAGTTGGTTTTCATGTCATCTACAGCATATGAGAAA AGCTACCTTTCTTTTGATTATGTACACAGATATCTAAATAAGGAAGTATGAGTTTCA CATGTATATCAAAAATACAACAGTTGCTTGTATTCAGTAGAGTTTTCTTGCCCACCT ATTTTGTGCTGGGTTCTACCTTAACCCAGAAGACACTATGAAAAACAAGACAGACTC CACTCAAAATTTATATGAACACCACTAGATACTTCCTGATCAAACATCAGTCAACAT ACTCTAAAGAATAACTCCAAGTCTTGGCCAGGCGCAGTGGCTCACACCTGTAATCCC AACACTTTGGGAGGCCAAGGTGGGTGGATCATCTAAGGCCGGGAGTTCAAGACCAGC CTGACCAACGTGGAGAAACCCCATCTCTACTAAAAATACAAAATTAGCCGGGCGTGG TAGCGCATGGCTGTAATCCTGGCTACTCAGGAGGCCGAGGCAGAAGAATTGCTTGAA CTGGGGAGGCAGAGGTTGCGGTGAGCCCAGATCGCGCCATTGCACTCCAGCCTGGGT AACAAGAGCAAAACTCTGTCCAAAAAAAAAAAAATAAAATAATAACTCCAAGCCTTT AAAAAATATCATCTGAAACTGTTACATCAGATTTCTGGCACTCTACTGACTGTGGAA GATAGCCAGCTGACTGGAAGATAGCCAGCTGATTAGTTCCCTGAAGAAACCTGAAGA CAGATACCTGGTTAACTAGATCAACTACACTGCCAACTTGTTTGATGCTGAGAGACA ATGGACTTATTCCATGGGGGAAGGGAAAAAAGAAGTCAATCACCAAATCTGAAGAAG TTAACCTAGATCTTTGAGGTTTGATTTGCAACTTTATATGCAGAGTATTATGTGGGT ATTTTCCCTTAAAATATTCAAAGGGATTTACATATGGGATTAGCTAATGAGCCTAGC CAAGACCTTCCCTGGAGGACAGGCTGGTCATTGCGGAGGTCCCTTCTGTGCTTCAGT GGGTTCATATCCTCTAGTCCGTATGATTTTCCTACGCTAATATGTCAAGGGCAGGAG AGGCAGCTCTGTTCTCCTAGCCTTTGTTGACTTGTCTGCAAAGCAGGAATCTGCCCA TTTGTTTCCAAGGAGCAAATGAGCTCATGAGAATGAAAGATGTTAACTTCATGCATT CTGTGCCATCTGAGCATTTCGGTATTATATGACTGGTGACCCTTGGCCCGTATTATA AATGCTTCCTATCCTGGGAGACCTCATGGATGAGTCTGAGAGGAAATTTGGCACCAA AATCACTCTCACTCTGGTTTCCAGTAGACTATAGAGGCAGAGAGGCATTTGAGAGGC TCCTGAGCAAAGTGTCCAGTGTAGCAGGAGCACTTCATTAATATTTATTGAGTTATA ATTAAATAAAAATTAATTTCTGATTTCTCAGTTTGGAGGTTAAGGCTCTAAATATAT TTTCTAACCTCTGCTAGGCTAACTTAAGCCAGGCCTTTTTCTTGCCTTCCCTTTCTC AAAACAGTCAGCACAGACTCAGTGGGAGCACAGAGGAGTGTGGTCACCTCCACCTGG CTCACCAGAGTCTTCATAGAGGAAGTGAAGCCTGGAAGAAACTGGGCGGGCCCCAGA TGACCACAGGGAAAGGGCATCTCAGATGGAGGAATTACCCTTGACTTAAAGCAGAAA AGAAAGATTTCTCAGTAACTCCAAAACTTGCTTGATAGGAGAATATTCCCTCAACCA ATTCCTAGGACAATATTTATTGGTAGATCAAGAATGTTTCCTCAATAACTCTAGTCT AGCTCCATGATCAGAACTAACACCCATTAAAAACATAAAATGTTCTTTCTGAACCGG TCTTCATGGTGCGTGAGAGCACCAAGCAGCTTTGGTATGCAGGAGGAGTTTTGCACA GAAGAGTGGCCTGCTCAAACCTGCCCACTGTTCTGTAGGTGATCTGGTGGATCTGGA AATTTATCCCAAGACAGGAATTTCCTAATATTCGAAGACATTTGAGGCTTTGGGAAA TTCTCTGCTGTGCATTTATTTGGCTCCTGTCATAAGCTTGTTTTTTAAAGAATGTAT CATAGCTCAAGTTTTTACTGCTGATTTTGTTAAATTCTGTATAGTATATTTTTTACG GAAAGGCACAGTCAGACATTCCTAATAGGGCTCATGTCAGAACTTCTGTTCCCAAGG CATTATCTCCATAGCAAAAATTAGTGCACTGTTTTCAAAAGTGAGGTGGGAAAATGC TTTTAAGATCATGTGATGTTCCCCTAAAAGGGGTTAATGGGGTGTATTCAGGGTTTG GGAGGGAGGAAGAAGCATGCTTTAGAAAACAGTAAATTTAGGGAGAAAATGCTTTGT TGGTTAAATGTCACTCAAAAGGCTGAATTCAAATCAATTCCACAAACATTTACTGAG TACCTACTGCCCCTGGGGACACAGAGATAAATTATTTAGTCTCAGACACACTCATTC TAACTTCCCAGCACCTCTACTGTCTGCAGATTCTTTAATTTATTTTGGTTGTATTAG CTAATTAATTCGTAAACTTTAGGCACATGGATCTATTCTCATTATGAAAATGGATGC CATTTGATTAAGGCTGATGACTAACAAAATGATTTGTGTTTACTCGAAGTGTTTTTT TAAAAATAGCTACTCAAGGATAGTTTTCCATAAATCAAGAAGGTAAAAAAGTTCCCA TTTTTTATTGTAGAATCCATTATTTAAACTACATGTAGAGACAGGTTATTATTTGCT ATATTCAAGTTTGGTCATCAATACCCTTAAAAATATTAGAATTTTATGGATGACCCA GAAATGCTTTGAAAATCTGTGTTCCTCAGCAAATACAGAGACCATGATCAAAATGCA CAGAATCACTAACATTTTGATGCTAGCATGGTTTCAGTCTATTTGGCAGAACAGAAT TGATTATGCTACTAAAATTTCTTTTTCTTTTTTTTTTTTTTTTTTTTTGAGACAGAG TCTTGCTTTGTCACCCAGGCTGAAGTGCAGTGGCAGGATCTCAGTTCACTGCAACCT CTGCCTCCCAGGTTCACGCCATTCTCCTGCTTCAGCCTCCCGAGTAGCTGGGACTAC AGGCTCCCACCACCATGCCCGGCTAATTTTTTGCATTTTTAGTAGAGACGGGGTTTC ACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCAGCC TTCCAAAGTGCTGGGATTACAGGCGTGAGCCACTGTGCCCGGACTCTGATTTTTTTT TTACTAAGGTACAGTAAGAAAAGGGAAAAGTGTACGTTTTCACTTCCTGAAATATGT CAGGTTGAATCAATAATAGAGCACACCAGAACTCTTGGCTCCATTTCAACCTAAACT ATTCAGTTCTCATCACCCCAGAGGAAATTCCGCCTCTGTGCTGGTCAGTAATCCCCC TGGATTATAAAAGTTTAACTAACTCACTGTGCACAAGGCACGGCCATTGCCAACATT CTCTTGCAAGGTATTTTCCCAAGCCCTTACCCAATTCTGTTTCCATGATTGTGACAT TGGGGATTAATTCTGCAAGACAGAACTGTTTATATTCTGTACCTTAAAAACACATGC AAACATCTCTTGCCTTAAGATTTCTGGCTTTCCTATGGCCCAGAGTCCTAGAAGTGT TTTGATATTTGTAGCAGAATTTTCAAGTGTACATCCTTATCCTGGATATTAACATTT TTGCATCATATTGGCAGCTGGACCTACAGAGAATTTAGTAGACTGTTAACCTAATAA GCCTTGAATCCTTTTGCACCAGTGGTGAGAGAATGTGGATCAGAGCCATCACCTCCA TGCCCCGTCACCCTCTAACAACCACATTTACAACTTCCCCAGCTCTGAGACACACTT GCCTCCACCCCTTCCATCACCCCATTTTAAGATGAAAATACCACACCAGCCTGGAAG GAAGAAGTTACTTGCCCAGGGCCACATAGTGAGTTAAGGGCTGATCTAGAGCTAGGA AGCTGTCTTCCTGAACCATAATCCTGGACTCTTCTAACCTCTCTACTCATCGCAAAT AGAGTTCATTTTAGTGATTTGAAGGAAGATGGGACAAGTATTTTCAAACACCTGTAG GACAACATGGAAGTGGGAGGAGACTTCTACTGTAGCTCCCCAGAGAAGAGAGCTAGG GCTACAGAGTTGCAGTTACAAGGTTGCCCTCTCTGGCTTGATCCCCAAAGGAATTTT CTACTCCAAAATAGAATTTTTCTAGGATGCTATTTCTCAGTCCCTGGAGATACTCAA ACAAAGGGCTTGTCACAAGGGTTTTTGTAGAAGCTATTCTTCACAGAGGTTGGGGGA GAGATTAAGCCAAAGGATCTCTGAGGTCTTTTTCAAATCTATAATTATGTGGCCTTT TGTTCATTGACTTCCATGTGTTCTAGTTGATCATTACAAACCTGGCAGGCCTTCTCA AGGGTTCAGTAATTAGCTGTCATTTCCCATTTGTCCAGAGAGTGTCCAACACAAAAT ACCCCTAAGATCTTGGCCAATAGAGAAATGTCATGGAATTTTAGAAATGACAGTATC TGCGGAGTTTATTCCAAGTTATATCATTTCAAAGATGAAGAAACCCAGGCTCAGAGG GAGCCATCACATCCACACCCTGTCACCCTTCGTGGCCAGTGCCAGACAGTAGCTAGT TGGATGCTAAAAGTAGAATTTAGATATCTTAACAATAAGCCCAGCAGTCTTTCAACT TCATTCGTAAATCATTTTTGTTTTGAGCATCTGTCACGTGGCAGCACTTGCCTGGAT ACTGGAGAGCTGAGAAGGAATGCGACAGGCAAGTCCTACTCTCACAGTGTATACATT CAGGAGGAACAAGACACACAGTGCCAAGTAAATAAAGTAGCTGAACTTCATCAAATG ATTTTATTCTTAAAGTCATTAAAGCATGTAATGTTCCCCTTTTTTTGTTTCAGGGGT GTACAGATTGAAGAAGTGTAGGTGTTTATGTGGTTTTAGTGACAAACCCCATGTGCT TTCATTGATTTTATGTTTTATGTTAAAACATCAACCGCAAGGTAAAATGCATATTGT ATGTTGTTGGATACGTACTTAACTGGTATGCATCCCATGTCTTTGGGTACTAGTGTA TGAATTCTAATCTCTGTAAATGAAATGTTGTATGTGTTAATATATTTAATAGATGTA ACTTAATAAACTGGCATTGAAGACTGAA(SEQIDNO:133) >NP_005109.2tumornecrosisfactorligandsuperfamily member15isoformVEGI-251precursor[Homosapiens] MAEDLGLSFGETASVEMLPEHGSCRPKARSSSARWALTCCLVLLPFLAGLTTYLLVS QLRAQGEACVQFQALKGQEFAPSHQQVYAPLRADGDKPRAHLTVVRQTPTQHFKNQF PALHWEHELGLAFTKNRMNYTNKFLLIPESGDYFIYSQVTFRGMTSECSEIRQAGRP NKPDSITVVITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAMESLQEGDKLMV NVSDISLVDYTKEDKTFFGAFLL(SEQIDNO:134) MouseTL1 >NM_177371.4Musmusculustumornecrosisfactor(ligand) superfamily,member15(Tnfsf15),mRNA ATCAGAAGTCTCTCCAAGACAGCAGAAGGATGGCAGAGGAGCTGGGGTTGGGCTTCG GAGAAGGAGTCCCAGTGGAAGTGCTGCCGGAAGGCTGTAGACACAGGCCAGAGGCCA GGGCCGGGCTAGCTGCCAGGAGCAAAGCCTGCCTGGCTCTCACCTGCTGCCTGTTGT CATTTCCCATCCTCGCAGGACTTAGCACCCTCCTAATGGCTGGCCAGCTCCGGGTCC CCGGAAAAGACTGTATGCTTCGGGCCATAACAGAAGAGAGATCTGAGCCTTCACCAC AGCAAGTTTACTCACCTCCCAGAGGCAAGCCGAGAGCACACCTGACAATTAAGAAAC AAACCCCAGCACCACATCTGAAAAATCAGCTCTCTGCTCTACACTGGGAACATGACC TAGGGATGGCCTTCACCAAGAACGGGATGAAGTACATCAACAAATCCCTGGTGATCC CAGAGTCAGGAGACTATTTCATCTACTCCCAGATCACATTCCGAGGGACCACATCTG TGTGTGGTGACATCAGTCGGGGGAGACGACCAAACAAGCCAGACTCCATCACCATGG TTATCACCAAGGTAGCAGACAGCTACCCTGAGCCTGCCCGCCTACTAACAGGGTCCA AGTCTGTGTGTGAAATAAGCAACAACTGGTTCCAGTCCCTCTACCTTGGGGCCACGT TCTCCTTGGAAGAAGGAGACAGACTAATGGTAAACGTCAGTGACATCTCCTTGGTGG ATTACACAAAAGAAGATAAAACTTTCTTTGGAGCTTTCTTGCTATAAGGAGGAGAAA ACCATCATTCCAAGGGGCTCCCCTGCCTCCTACTTTCCAATTTCCTTTTCTCATATG GATCTATAAACAGGGGCTTTAGAGGGATCAGGGAAGGGGACAGTGGTTTAGCTATAT AATTTAGGAACCCAATATTGATCCGTATATGCCTTATGGACTAAAATAGTAAATGGA AAACCCAGTACAGCTCATGTTTGATAGAGACCTGCTGGGTTTTAAAAATTGAAACAC GCCTCATCCAATGGCACAATCTACTGATTTCAGGACAGAACCTTTCCACAGTGCCCT CTGTCCAAGTCCTTTCTGAATTCAGCAGTTCAGTTAGAGCTGAATTCGACAATGAAC TTACTCCAGATCAAGAGCTAAAGACAGAATCCAAAGAAAGACTGAGAAAATGATGTT ATTTCTCCAAGAGGCAATGCATTTCCACATTCTTTTGTGCCTAACCTAAAAAATAAG AAAGAAGAAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGA AGGAAGGAAGGAAGGAAGGAAGGGACAAGAAAAGACAAGACAAGACAAGAAAAAAGA AAAAATGGTATTTCTCGTGAATATTCCCTAAAAGGAATTGGTTTTCTGCTGTGAAGG AGAAACCTCACCTTTCTTCTGATTGCATCCTTTAGTATCCAAACATACAAGTGGGAA TTCCAAATGCACATGGAACATAGAACACTTTTATTATTGTGAGAACATGTTTATTGA GTACCTACTATGCTCTGGGCACTCAGCCCACAGGACCATGAAGAGAAAGTCAAATTT TCTTAAAAACTAAATGAATCCTCAATACATACTTCCTGATCAACTACCACTCAAAAT GTATAACTTCCAAAGTATAACTTCAAGTCAGCCATCTAGGTGGTTTCTTGGGTAAAG GTGCTTGTCATTAAGCCTGACACCTGGGTTTGACCTCCCAGAACCCAAAAGCTGGAA GGAGAGAATTGGTTCCCACAAATTATCCTCAAACCCCCATACAAATGATGTGGCATG CACACATGTAACTAAATAAATAAGTGTAAAACAAAAACAAAAACAAAATTTTAAAGA AAAATTTCAAGTCCTGAAAGACAGCATTCCTGAGAATGTTGTCTCCATCGTTGTCCA GTATAGGCTAACCAGCTGATAGAGACACTGAAGGAATTTAAAGACAGACATCAAGTG AAATGGAGCACTGTAGAAACACTTGATTCATGCCAGGAGTCAATGTACTATGAAGAC CAACAACAAAGTGTCAGTCATCAAATCCAGAGGTGTTTATCTAGATCTGCTTTCAAG TTTGGTTTGCAGCCTTTATATAGTCTCTATTACAAATGCTCGTGTCATGGTAGATGC CACAAGGAGTCAGAGGGTAAACTTAGCCCCAAACCACTGCTGAGCCATCTTCTAGGA AACCTTCGAAGCAGAGCTGGGCAGCGTGACTCCCACACAATGACTGGGAAAGTAGTA GCTGATCAAAATTTGTTGAGTAATAATTTGTTAGAAAATTCATCTCCACTGCCTACT AAACCTAAGTTGTATACTATCTAGCTTCTGCTAAGCCAACTTACATTGGCCACTTTT TCTGTCTTCAACTTCTTGAAGTATCACAGGTCTCAGTGAGAACACAGGGAAAGGTGA GGTCGCCTTCCCCTGGTTCTTCATAGGGGAAACCACACCTGAAAGAAGATGAGCAGC CTGAGGTGACCTGGAGGAAGGGCTGTCTCAGAAGAAGGACTTATTTTTTGGCTTAGG TCTAAAACCTTGAGAGTAATGCTCACTGGTCAATTGAGGATGCTTTATCAATGACTC CAGTCTGACTCCAAGGTCAGAAAGGAGAGTGAGATGCTCTCTCTGCCTGCATATATC TTCATGGAACATGAGAATATTGAGCAACATAGACTTATAGGAAAACACTTGCCCAAA AGTAGCCAGAGTGACCTGGTCATCCCCTCTACTAAACCCAAGCTTTGTGTCAAGGGC CTTCAAAGCTGCCCAGAAGTGATCTGGATGGCTTGGGAATTTATCCAAGACAGGAAT TTCCTGACAGCCAAAGATGCTTGAGTCCTTGTGCCTGACATGCATTTATTTTGCCCC TGTTTATTGAAGACTGTAACTGTTGATTTGTGGGTATACATACATACATACATACAT ACATACATACATACATACATATGCTGTCATGAAGGCAGCATCAAACATTACTAATTG GACTCAAACCAGCATTTCTGTTTCCAAGATACTAAGTATTCCCATGCAAACAGGAGC ATGCTATTTTTCTAAAGCAAAATGAAAAAAATAGTTTTGAAAGTATATATATGATGG AGTCAAGTGTAATGGCATACATCTGTAAACCCAGCACATGGGATGCTGAGCCAGGAG GATTGCCGTGAGTTTGAGGAGAACAGGGGCTAAATAGTAATTTTCAGGAAAGCCTTG CCTATATAACAAGACCTTGTCTCAAATGAAAAAAAAAAAAAAAATAGACCCCAGGCT GGTCCTTGGAGATAAGGTAATATATTCATTGGGTGAGGGGGTGTGTGTTTTGGAAAA TAGTTAATTTAGTGAGAAATGCTTTTCGGTCAAATGCATCTCAAAGGCTGCTGAATT CAAATCGGGTCTGTAAATGCTTACCTAGTGCTTGCTTGCCCTGGGGACAGAGACATA AATTACTTTAGTCTCAGATCCACTCGTTCTAACAGATTGGCATCTCCATCGTCTGTG GAGCTTTTAATCACTCTGTTTGTATTAGCTAATTAATTAGCTAACTTGAGACACACT GATATTTTCTTATTATAAACATGGGTGCCATTTGATAAAAGACAATCATTAACAAAA TGGTTCGAATTTCCGCTTAAGTGATCTTCTTTTTTCCTTTTCATTTTTTTTAACTAG CTAATCAAAGGTAGTTTCCCAAAAATAAATGCAAAGGGAGTATAAAGAAAAAATTCC CTGTGGTGGGAGCTAGTATTGAAACAACAGTATCAAAGAGGCTGTTACCTACTGGCC TCAAATTTTGGCAGGAACGCCTTTGAAAATGTTAGAACTTTACGGACAGCCTAGAGG TGCTTTGAAAAGTCTCTGTTGCCAACAAAAGCCATTAATCAGCATGCGGCACAGGTT ACTCAAATTTTGACCTTGACTGTTTTTTAGATCTGTTACACAGAACACAACTTCTGG GCTGTAATCTCTGATGTGGATTTGGTGATTTACTAAGGTACCGTGGGAAACAAGGAA AGTGTACTTGTACCACATCGTTTCTCAGTGCATGTCAGAGTCTACTCAACAGCAGGG CATGCCAGAGCCTTGGATACATTCCGGGACAAACTATGTCACTCCTAAGGAAATTCC AAGTGTGTGCCTGTCAAGCACTCTGGATCATAGAAGCCCACGAGTTCACTGTGCACA AGGCACAGCCATGGCCAGCACTCTCTTGCATGGTATTTCTCTTAAGCTCTTACTCAA TCACGGTCCCATGATTGTGACATTGGGGATTAATTGCTTGAGCAGGTTTATTTACAG TCTGTTCCTTGCAAAATACATGCAGATATGTCTGGCCTCAAAATCCCCTGATTGTTT TAGGGCTTAGAGAATACTGGGGATGTTTTTGCTGTTTTCAGATGTACTTTATTTAAG CTTGCAGAATTACCCTGAATATTAACAGTGTTCTAAGATATTGCCTGCTAGCTTCTG GCTAATTTACTAGTGGTGACAGTATCAGATCAGAGTATCTATATTTATGTCTTGCTA TTATAGTTAAAACTTCCTGATCTCTGTAACACACTCACCCCTACCTCATCTATCTAC CCATCTTGTGGATGTAGCTGTGAGAAGACTCACAAGCCCGAGTTGCAGTTACTTTTC TGAAGCAACATAGTATGTTAATGGAATGGCCAGAACTCTACTCTTGGCACATGGCAC TGAATTTGATGCCACTAAAAGAAAAATTGAAGGCAGAAATATTTTTTACTATGCATG GGACAACGTAGAAGAGCAAGGAGACTGCTTACACATGGTGGTCACATCTCTGGCTTC ATCCCTAAACCAATTTTCTGACCCCAAGTCGATTTTTTTTCATGTAGTTATTGTTCA TTTTCTGGAAAGAGTCAAGCAAAAAGAGAGTTTTATAGAAACCATTGCATCATGGAG GTCAGGGGAGGGATTAAGCCAAAGAATTCCTTCTCCAAATCTATAGCCATATGGCCA CCCTTTGGTGTACTTCTATTTGATCATGACAAACCTGAGAGCCCTGCCCAGAGTTCA GTGGATCCTAATGAACTCCAAGAGTAATTCATTCCCTCACCAACTCTAGGGGCTTGG CCAGTGCAGAAAATGTCATGGGATTTTAAAGTTAACATGAGCTGCTATCCAAACTTA TGTCTCTTTAAGAATGGAGAGACACAGGCCAGGAGAGGTAACATATGAAGCCTGGTA TTGGGCAGTAGCTTGATGGAGTATTGAGGCTAAAAGTAGACTTCCTGCCCCTGACCA TACACAACACCCTTTCAGTTTGATCCATGGTGGTCTTATTCTACTTTATTTTGAGCA CCTGTCACACCTAGTTACTGTCATGCCAAGAAGGTCCATAACAGGCAAATCCTACTC TGCTGTGTGCACACAAGAGGAAGGAGGCTCACAGTAGCAAGTAAACAGATAAGCAAA CGTACACGATTTTCGTCTTAAAGTCATTAAGACACACGCGTACCCCTCTTTTGTTTC AGAGGGTATACAGGCTGAACAGATGTCAGTGTTCACCTATTCTTATTGATAAGCCCC ATGTGCTTTCATTGGTTGAATGTTTTATGTTAAAACGTCATATTGCCATCGTAAAAT GCATATTGTATGTTGTTGGGTATATAATTAACTAATATGCATCGCATGTATGAATTC TAATCTCTGTAAATGAAAACTTATATATGTTAACATATGTAATAGTTATAATTTAAT AAACTGACACTGGAGACTAC(SEQIDNO:135) >NP_796345.4tumornecrosisfactorligandsuperfamily member15[Musmusculus] MAEELGLGFGEGVPVEVLPEGCRHRPEARAGLAARSKACLALTCCLLSFPILAGLST LLMAGQLRVPGKDCMLRAITEERSEPSPQQVYSPPRGKPRAHLTIKKQTPAPHLKNQ LSALHWEHDLGMAFTKNGMKYINKSLVIPESGDYFIYSQITFRGTTSVCGDISRGRR PNKPDSITMVITKVADSYPEPARLLTGSKSVCEISNNWFQSLYLGATFSLEEGDRLM VNVSDISLVDYTKEDKTFFGAFLL(SEQIDNO:136) HumanCD80 >NM_005191.4HomosapiensCD80molecule(CD80),mRNA AAACCCTCTGTAAAGTAACAGAAGTTAGAAGGGGAAATGTCGCCTCTCTGAAGATTA CCCAAAGAAAAAGTGATTTGTCATTGCTTTATAGACTGTAAGAAGAGAACATCTCAG AAGTGGAGTCTTACCCTGAAATCAAAGGATTTAAAGAAAAAGTGGAATTTTTCTTCA GCAAGCTGTGAAACTAAATCCACAACCTTTGGAGACCCAGGAACACCCTCCAATCTC TGTGTGTTTTGTAAACATCACTGGAGGGTCTTCTACGTGAGCAATTGGATTGTCATC AGCCCTGCCTGTTTTGCACCTGGGAAGTGCCCTGGTCTTACTTGGGTCCAAATTGTT GGCTTTCACTTTTGACCCTAAGCATCTGAAGCCATGGGCCACACACGGAGGCAGGGA ACATCACCATCCAAGTGTCCATACCTCAATTTCTTTCAGCTCTTGGTGCTGGCTGGT CTTTCTCACTTCTGTTCAGGTGTTATCCACGTGACCAAGGAAGTGAAAGAAGTGGCA ACGCTGTCCTGTGGTCACAATGTTTCTGTTGAAGAGCTGGCACAAACTCGCATCTAC TGGCAAAAGGAGAAGAAAATGGTGCTGACTATGATGTCTGGGGACATGAATATATGG CCCGAGTACAAGAACCGGACCATCTTTGATATCACTAATAACCTCTCCATTGTGATC CTGGCTCTGCGCCCATCTGACGAGGGCACATACGAGTGTGTTGTTCTGAAGTATGAA AAAGACGCTTTCAAGCGGGAACACCTGGCTGAAGTGACGTTATCAGTCAAAGCTGAC TTCCCTACACCTAGTATATCTGACTTTGAAATTCCAACTTCTAATATTAGAAGGATA ATTTGCTCAACCTCTGGAGGTTTTCCAGAGCCTCACCTCTCCTGGTTGGAAAATGGA GAAGAATTAAATGCCATCAACACAACAGTTTCCCAAGATCCTGAAACTGAGCTCTAT GCTGTTAGCAGCAAACTGGATTTCAATATGACAACCAACCACAGCTTCATGTGTCTC ATCAAGTATGGACATTTAAGAGTGAATCAGACCTTCAACTGGAATACAACCAAGCAA GAGCATTTTCCTGATAACCTGCTCCCATCCTGGGCCATTACCTTAATCTCAGTAAAT GGAATTTTTGTGATATGCTGCCTGACCTACTGCTTTGCCCCAAGATGCAGAGAGAGA AGGAGGAATGAGAGATTGAGAAGGGAAAGTGTACGCCCTGTATAACAGTGTCCGCAG AAGCAAGGGGCTGAAAAGATCTGAAGGTCCCACCTCCATTTGCAATTGACCTCTTCT GGGAACTTCCTCAGATGGACAAGATTACCCCACCTTGCCCTTTACGTATCTGCTCTT AGGTGCTTCTTCACTTCAGTTGCTTTGCAGGAAGTGTCTAGAGGAATATGGTGGGCA CAGAAGTAGCTCTGGTGACCTTGATCAAGGTGTTTTGAAATGCAGAATTCTTGAGTT CTGGAAGGGACTTTAGAGAATACCAGTGTTATTAATGACAAAGGCACTGAGGCCCAG GGAGGTGACCCGAATTATAAAGGCCAGCGCCAGAACCCAGATTTCCTAACTCTGGTG CTCTTTCCCTTTATCAGTTTGACTGTGGCCTGTTAACTGGTATATACATATATATGT CAGGCAAAGTGCTGCTGGAAGTAGAATTTGTCCAATAACAGGTCAACTTCAGAGACT ATCTGATTTCCTAATGTCAGAGTAGAAGATTTTATGCTGCTGTTTACAAAAGCCCAA TGTAATGCATAGGAAGTATGGCATGAACATCTTTAGGAGACTAATGGAAATATTATT GGTGTTTACCCAGTATTCCATTTTTTTCATTGTGTTCTCTATTGCTGCTCTCTCACT CCCCCATGAGGTACAGCAGAAAGGAGAACTATCCAAAACTAATTTCCTCTGACATGT AAGACGAATGATTTAGGTACGTCAAAGCAGTAGTCAAGGAGGAAAGGGATAGTCCAA AGACTTAACTGGTTCATATTGGACTGATAATCTCTTTAAATGGCTTTATGCTAGTTT GACCTCATTTGTAAAATATTTATGAGAAAGTTCTCATTTAAAATGAGATCGTTGTTT ACAGTGTATGTACTAAGCAGTAAGCTATCTTCAAATGTCTAAGGTAGTAACTTTCCA TAGGGCCTCCTTAGATCCCTAAGATGGCTTTTTCTCCTTGGTATTTCTGGGTCTTTC TGACATCAGCAGAGAACTGGAAAGACATAGCCAACTGCTGTTCATGTTACTCATGAC TCCTTTCTCTAAAACTGCCTTCCACAATTCACTAGACCAGAAGTGGACGCAACTTAA GCTGGGATAATCACATTATCATCTGAAAATCTGGAGTTGAACAGCAAAAGAAGACAA CATTTCTCAAATGCACATCTCATGGCAGCTAAGCCACATGGCTGGGATTTAAAGCCT TTAGAGCCAGCCCATGGCTTTAGCTACCTCACTATGCTGCTTCACAAACCTTGCTCC TGTGTAAAACTATATTCTCAGTGTAGGGCAGAGAGGTCTAACACCAACATAAGGTAC TAGCAGTGTTTCCCGTATTGACAGGAATACTTAACTCAATAATTCTTTTCTTTTCCA TTTAGTAACAGTTGTGATGACTATGTTTCTATTCTAAGTAATTCCTGTATTCTACAG CAGATACTTTGTCAGCAATACTAAGGGAAGAAACAAAGTTGAACCGTTTCTTTAATA A(SEQIDNO:137) >NP_005182.1T-lymphocyteactivationantigenCD80 precursor[Homosapiens] MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVE ELAQTRIYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTY ECVVLKYEKDAFKREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEP HLSWLENGEELNAINTTVSQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQT FNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFAPRCRERRRNERLRRESV RPV(SEQIDNO:138) MouseCD80 >NM_009855.2MusmusculusCD80antigen(Cd80),transcript variant2,mRNA GAGTTTTATACCTCAATAGACTCTTACTAGTTTCTCTTTTTCAGGTTGTGAAACTCA ACCTTCAAAGACACTCTGTTCCATTTCTGTGGACTAATAGGATCATCTTTAGCATCT GCCGGGTGGATGCCATCCAGGCTTCTTTTTCTACATCTCTGTTTCTCGATTTTTGTG AGCCTAGGAGGTGCCTAAGCTCCATTGGCTCTAGATTCCTGGCTTTCCCCATCATGT TCTCCAAAGCATCTGAAGCTATGGCTTGCAATTGTCAGTTGATGCAGGATACACCAC TCCTCAAGTTTCCATGTCCAAGGCTCATTCTTCTCTTTGTGCTGCTGATTCGTCTTT CACAAGTGTCTTCAGATGTTGATGAACAACTGTCCAAGTCAGTGAAAGATAAGGTAT TGCTGCCTTGCCGTTACAACTCTCCTCATGAAGATGAGTCTGAAGACCGAATCTACT GGCAAAAACATGACAAAGTGGTGCTGTCTGTCATTGCTGGGAAACTAAAAGTGTGGC CCGAGTATAAGAACCGGACTTTATATGACAACACTACCTACTCTCTTATCATCCTGG GCCTGGTCCTTTCAGACCGGGGCACATACAGCTGTGTCGTTCAAAAGAAGGAAAGAG GAACGTATGAAGTTAAACACTTGGCTTTAGTAAAGTTGTCCATCAAAGCTGACTTCT CTACCCCCAACATAACTGAGTCTGGAAACCCATCTGCAGACACTAAAAGGATTACCT GCTTTGCTTCCGGGGGTTTCCCAAAGCCTCGCTTCTCTTGGTTGGAAAATGGAAGAG AATTACCTGGCATCAATACGACAATTTCCCAGGATCCTGAATCTGAATTGTACACCA TTAGTAGCCAACTAGATTTCAATACGACTCGCAACCACACCATTAAGTGTCTCATTA AATATGGAGATGCTCACGTGTCAGAGGACTTCACCTGGGAAAAACCCCCAGAAGACC CTCCTGATAGCAAGAACACACTTGTGCTCTTTGGGGCAGGATTCGGCGCAGTAATAA CAGTCGTCGTCATCGTTGTCATCATCAAATGCTTCTGTAAGCACAGAAGCTGTTTCA GAAGAAATGAGGCAAGCAGAGAAACAAACAACAGCCTTACCTTCGGGCCTGAAGAAG CATTAGCTGAACAGACCGTCTTCCTTTAGTTCTTCTCTGTCCATGTGGGATACATGG TATTATGTGGCTCATGAGGTACAATCTTTCTTTCAGCACCGTGCTAGCTGATCTTTC GGACAACTTGACACAAGATAGAGTTAACTGGGAAGAGAAAGCCTTGAATGAGGATTT CTTTCCATCAGGAAGCCTACGGGCAAGTTTGCTGGGCCTTTGATTGCTTGATGACTG AAGTGGAAAGGCTGAGCCCACTGTGGGTGGTGCTAGCCCTGGGCAGGGGCAGGTGAC CCTGGGTGGTATAAGAAAAAGAGCTGTCACTAAAAGGAGAGGTGCCTAGTCTTACTG CAACTTGATATGTCATGTTTGGTTGGTGTCTGTGGGAGGCCTGCCCTTTTCTGAAGA GAAGTGGTGGGAGAGTGGATGGGGTGGGGGCAGAGGAAAAGTGGGGGAGAGGGCCTG GGAGGAGAGGAGGGAGGGGGACGGGGTGGGGGTGGGGAAAACTATGGTTGGGATGTA AAAACGATAATAATATAAATATTAAATAAAAAGAGAGTATTGAGCAAA(SEQID NO:139) >NP_033985.3T-lymphocyteactivationantigenCD80 precursor[Musmusculus] MACNCQLMQDTPLLKFPCPRLILLFVLLIRLSQVSSDVDEQLSKSVKDKVLLPCRYN SPHEDESEDRIYWQKHDKVVLSVIAGKLKVWPEYKNRTLYDNTTYSLIILGLVLSDR GTYSCVVQKKERGTYEVKHLALVKLSIKADESTPNITESGNPSADTKRITCFASGGF PKPRFSWLENGRELPGINTTISQDPESELYTISSQLDENTTRNHTIKCLIKYGDAHV SEDFTWEKPPEDPPDSKNTLVLFGAGFGAVITVVVIVVIIKCFCKHRSCFRRNEASR ETNNSLTFGPEEALAEQTVFL(SEQIDNO:140) HumanCD86 >NM_175862.5HomosapiensCD86molecule(CD86), transcriptvariant1,mRNA AGTCATTGCCGAGGAAGGCTTGCACAGGGTGAAAGCTTTGCTTCTCTGCTGCTGTAA CAGGGACTAGCACAGACACACGGATGAGTGGGGTCATTTCCAGATATTAGGTCACAG CAGAAGCAGCCAAAATGGATCCCCAGTGCACTATGGGACTGAGTAACATTCTCTTTG TGATGGCCTTCCTGCTCTCTGGTGCTGCTCCTCTGAAGATTCAAGCTTATTTCAATG AGACTGCAGACCTGCCATGCCAATTTGCAAACTCTCAAAACCAAAGCCTGAGTGAGC TAGTAGTATTTTGGCAGGACCAGGAAAACTTGGTTCTGAATGAGGTATACTTAGGCA AAGAGAAATTTGACAGTGTTCATTCCAAGTATATGGGCCGCACAAGTTTTGATTCGG ACAGTTGGACCCTGAGACTTCACAATCTTCAGATCAAGGACAAGGGCTTGTATCAAT GTATCATCCATCACAAAAAGCCCACAGGAATGATTCGCATCCACCAGATGAATTCTG AACTGTCAGTGCTTGCTAACTTCAGTCAACCTGAAATAGTACCAATTTCTAATATAA CAGAAAATGTGTACATAAATTTGACCTGCTCATCTATACACGGTTACCCAGAACCTA AGAAGATGAGTGTTTTGCTAAGAACCAAGAATTCAACTATCGAGTATGATGGTGTTA TGCAGAAATCTCAAGATAATGTCACAGAACTGTACGACGTTTCCATCAGCTTGTCTG TTTCATTCCCTGATGTTACGAGCAATATGACCATCTTCTGTATTCTGGAAACTGACA AGACGCGGCTTTTATCTTCACCTTTCTCTATAGAGCTTGAGGACCCTCAGCCTCCCC CAGACCACATTCCTTGGATTACAGCTGTACTTCCAACAGTTATTATATGTGTGATGG TTTTCTGTCTAATTCTATGGAAATGGAAGAAGAAGAAGCGGCCTCGCAACTCTTATA AATGTGGAACCAACACAATGGAGAGGGAAGAGAGTGAACAGACCAAGAAAAGAGAAA AAATCCATATACCTGAAAGATCTGATGAAGCCCAGCGTGTTTTTAAAAGTTCGAAGA CATCTTCATGCGACAAAAGTGATACATGTTTTTAATTAAAGAGTAAAGCCCATACAA GTATTCATTTTTTCTACCCTTTCCTTTGTAAGTTCCTGGGCAACCTTTTTGATTTCT TCCAGAAGGCAAAAAGACATTACCATGAGTAATAAGGGGGCTCCAGGACTCCCTCTA AGTGGAATAGCCTCCCTGTAACTCCAGCTCTGCTCCGTATGCCAAGAGGAGACTTTA ATTCTCTTACTGCTTCTTTTCACTTCAGAGCACACTTATGGGCCAAGCCCAGCTTAA TGGCTCATGACCTGGAAATAAAATTTAGGACCAATACCTCCTCCAGATCAGATTCTT CTCTTAATTTCATAGATTGTGTTTTTTTTTTAAATAGACCTCTCAATTTCTGGAAAA CTGCCTTTTATCTGCCCAGAATTCTAAGCTGGTGCCCCACTGAATTTTGTGTGTACC TGTGACTAAACAACTACCTCCTCAGTCTGGGTGGGACTTATGTATTTATGACCTTAT AGTGTTAATATCTTGAAACATAGAGATCTATGTACTGTAATAGTGTGATTACTATGC TCTAGAGAAAAGTCTACCCCTGCTAAGGAGTTCTCATCCCTCTGTCAGGGTCAGTAA GGAAAACGGTGGCCTAGGGTACAGGCAACAATGAGCAGACCAACCTAAATTTGGGGA AATTAGGAGAGGCAGAGATAGAACCTGGAGCCACTTCTATCTGGGCTGTTGCTAATA TTGAGGAGGCTTGCCCCACCCAACAAGCCATAGTGGAGAGAACTGAATAAACAGGAA AATGCCAGAGCTTGTGAACCCTGTTTCTCTTGAAGAACTGACTAGTGAGATGGCCTG GGGAAGCTGTGAAAGAACCAAAAGAGATCACAATACTCAAAAGAGAGAGAGAGAGAA AAAAGAGAGATCTTGATCCACAGAAATACATGAAATGTCTGGTCTGTCCACCCCATC AACAAGTCTTGAAACAAGCAACAGATGGATAGTCTGTCCAAATGGACATAAGACAGA CAGCAGTTTCCCTGGTGGTCAGGGAGGGGTTTTGGTGATACCCAAGTTATTGGGATG TCATCTTCCTGGAAGCAGAGCTGGGGAGGGAGAGCCATCACCTTGATAATGGGATGA ATGGAAGGAGGCTTAGGACTTTCCACTCCTGGCTGAGAGAGGAAGAGCTGCAACGGA ATTAGGAAGACCAAGACACAGATCACCCGGGGCTTACTTAGCCTACAGATGTCCTAC GGGAACGTGGGCTGGCCCAGCATAGGGCTAGCAAATTTGAGTTGGATGATTGTTTTT GCTCAAGGCAACCAGAGGAAACTTGCATACAGAGACAGATATACTGGGAGAAATGAC TTTGAAAACCTGGCTCTAAGGTGGGATCACTAAGGGATGGGGCAGTCTCTGCCCAAA CATAAAGAGAACTCTGGGGAGCCTGAGCCACAAAAATGTTCCTTTATTTTATGTAAA CCCTCAAGGGTTATAGACTGCCATGCTAGACAAGCTTGTCCATGTAATATTCCCATG TTTTTACCCTGCCCCTGCCTTGATTAGACTCCTAGCACCTGGCTAGTTTCTAACATG TTTTGTGCAGCACAGTTTTTAATAAATGCTTGTTACATTCA(SEQIDNO: 141) >NP_787058.5T-lymphocyteactivationantigenCD86isoform 1precursor[Homosapiens] MDPQCTMGLSNILFVMAFLLSGAAPLKIQAYFNETADLPCQFANSQNQSLSELVVFW QDQENLVLNEVYLGKEKFDSVHSKYMGRTSFDSDSWTLRLHNLQIKDKGLYQCIIHH KKPTGMIRIHQMNSELSVLANFSQPEIVPISNITENVYINLTCSSIHGYPEPKKMSV LLRTKNSTIEYDGVMQKSQDNVTELYDVSISLSVSFPDVTSNMTIFCILETDKTRLL SSPFSIELEDPQPPPDHIPWITAVLPTVIICVMVFCLILWKWKKKKRPRNSYKCGTN TMEREESEQTKKREKIHIPERSDEAQRVFKSSKTSSCDKSDTCF(SEQIDNO: 142) MouseCD86 >NM_019388.3MusmusculusCD86antigen(Cd86),mRNA ATTGCTGAGGAAGAAAGAGGAGCAAGCAGACGCGTAAGAGTGGCTCCTGTAGGCAGC ACGGACTTGAACAACCAGACTCCTGTAGACGTGTTCCAGAACTTACGGAAGCACCCA CGATGGACCCCAGATGCACCATGGGCTTGGCAATCCTTATCTTTGTGACAGTCTTGC TGATCTCAGATGCTGTTTCCGTGGAGACGCAAGCTTATTTCAATGGGACTGCATATC TGCCGTGCCCATTTACAAAGGCTCAAAACATAAGCCTGAGTGAGCTGGTAGTATTTT GGCAGGACCAGCAAAAGTTGGTTCTGTACGAGCACTATTTGGGCACAGAGAAACTTG ATAGTGTGAATGCCAAGTACCTGGGCCGCACGAGCTTTGACAGGAACAACTGGACTC TACGACTTCACAATGTTCAGATCAAGGACATGGGCTCGTATGATTGTTTTATACAAA AAAAGCCACCCACAGGATCAATTATCCTCCAACAGACATTAACAGAACTGTCAGTGA TCGCCAACTTCAGTGAACCTGAAATAAAACTGGCTCAGAATGTAACAGGAAATTCTG GCATAAATTTGACCTGCACGTCTAAGCAAGGTCACCCGAAACCTAAGAAGATGTATT TTCTGATAACTAATTCAACTAATGAGTATGGTGATAACATGCAGATATCACAAGATA ATGTCACAGAACTGTTCAGTATCTCCAACAGCCTCTCTCTTTCATTCCCGGATGGTG TGTGGCATATGACCGTTGTGTGTGTTCTGGAAACGGAGTCAATGAAGATTTCCTCCA AACCTCTCAATTTCACTCAAGAGTTTCCATCTCCTCAAACGTATTGGAAGGAGATTA CAGCTTCAGTTACTGTGGCCCTCCTCCTTGTGATGCTGCTCATCATTGTATGTCACA AGAAGCCGAATCAGCCTAGCAGGCCCAGCAACACAGCCTCTAAGTTAGAGCGGGATA GTAACGCTGACAGAGAGACTATCAACCTGAAGGAACTTGAACCCCAAATTGCTTCAG CAAAACCAAATGCAGAGTGAAGGCAGTGAGAGCCTGAGGAAAGAGTTAAAAATTGCT TTGCCTGAAATAAGAAGTGCAGAGTTTCTCAGAATTCAAAAATGTTCTCAGCTGATT GGAATTCTACAGTTGAATAATTAAAGAACAAAATACACAACAGTGTCCATATTTTAT CCTGTTTCCTTTCCAAGTTTTTGGGCAATGTCAATTGTGTCCCCTATGCCAGGAGCA GACATCTATTTTGTCTTGCTTTGTTTAACTCAGTGCACACTCATAGGCCAAGAGCAC TGAAATGGCTTCTTTCCCAGGAATAACATTTTGGATCAATCTCTCCTACTTGAGATC AGATTCTTCTTCTAATTTTGCATAGTGTGTTTTTATATGGAACTCCTTGTTGTAGGA ATACTGGCTTTTATCTGTCTTGCACACTTGCATACTTATATACTTATACCTGGACAG CTACCTCTTCAGTCAGGATGGGAGTGGTATATTTGGTGATGTTATTTGATGTGTTCG TGTTGCTATCTTAAAACAGCAAAGAGCATATACTATAGTAGCTCAACTACAATGATC TAGAGAAAGACCCAGCACTTATAAGAAACACTGTCCCTCCATCAGGGTCAATAATGA ATACAATGACCTAAGTAATATACAGGTGACAGCAACAGCACAGAGTTCTCAGTGCTG GCAAATCAAGAAACACAAATATGGAACCATCTCTAGATCCAAGAGCCACTCCTACCT GGGCTGCCACAGATACTGGAAGAATCCACCTGCCTGGCCAGCAAGTCACAACTTAGC AGGCAGCACTGAAGAAAGCAAGATGTACTGTATGCCCTTTTAAGAAAATGCCTGGAA AGGTCTGGAGAATGCTGTGCAAGGATAAGACAGCCAAGCACTCAAAACCAGGAGACA TCACTAGAATCCAACCAACAAATGTTTATGGAAGGACTGATCTGCCCAGTCCATTGA AAAGTCAAGAGGTCAGAGATAGACCAGTGTGTGTCTCAATGGATGTAGATATCAGCC ACCTCGGTGCTCAACAGGTATTTTATGATCTCCTTGTTTCAAATTCATCTAGATGTA GAACTAGGGAGAGAGCAGTCACATTGATGAAAGGCTAGGACTCTTTCAGCTCATGGC TTGTGTGGAAGGAGGGAAAGCAGAAATCACAACACTCTGAGACTACTGTAGTCTGCA GATACCTGAGTGGGTGTGGCTTGGCCTTTCAAAGGACAAAGAGCAACTAATGCTGAA AGCACATAGTGTATCTATACGGCATGGAATAGTCATCACCCAGACTTAAAGAGAACT TTGGCAGGTCTGAGCAGCAAAATATTGTTGTTTCCATTTTACATAAAGGGCCCTGGA GGGCTATAGACTATTCCGCTGGCAGGGCTCATGCTTGTAATGTGTCCATCTTGATTC ACCCTGTGCAGACTCTTAAGATCTGGCCAGTTACCAACATGTTCTGTACAGAGTGGA TTTCAATAAAGTTTTCTTGAATTTTTTCAAG (SEQIDNO:143) >NP_062261.3T-lymphocyteactivationantigenCD86 precursor[Musmusculus] MDPRCTMGLAILIFVTVLLISDAVSVETQAYFNGTAYLPCPFTKAQNISLSELVVFW QDQQKLVLYEHYLGTEKLDSVNAKYLGRTSFDRNNWTLRLHNVQIKDMGSYDCFIQK KPPTGSIILQQTLTELSVIANFSEPEIKLAQNVTGNSGINLTCTSKQGHPKPKKMYF LITNSTNEYGDNMQISQDNVTELFSISNSLSLSFPDGVWHMTVVCVLETESMKISSK PLNFTQEFPSPQTYWKEITASVTVALLLVMLLIIVCHKKPNQPSRPSNTASKLERDS NADRETINLKELEPQIASAKPNAE(SEQIDNO:144) HumanLFA-3 >NM_001779.3HomosapiensCD58molecule(CD58), (CD58) transcriptvariant1,mRNA GAACTTAGGGCTGCTTGTGGCTGGGCACTCGCGCAGAGGCCGGCCCGACGAGCCATG GTTGCTGGGAGCGACGCGGGGCGGGCCCTGGGGGTCCTCAGCGTGGTCTGCCTGCTG CACTGCTTTGGTTTCATCAGCTGTTTTTCCCAACAAATATATGGTGTTGTGTATGGG AATGTAACTTTCCATGTACCAAGCAATGTGCCTTTAAAAGAGGTCCTATGGAAAAAA CAAAAGGATAAAGTTGCAGAACTGGAAAATTCTGAATTCAGAGCTTTCTCATCTTTT AAAAATAGGGTTTATTTAGACACTGTGTCAGGTAGCCTCACTATCTACAACTTAACA TCATCAGATGAAGATGAGTATGAAATGGAATCGCCAAATATTACTGATACCATGAAG TTCTTTCTTTATGTGCTTGAGTCTCTTCCATCTCCCACACTAACTTGTGCATTGACT AATGGAAGCATTGAAGTCCAATGCATGATACCAGAGCATTACAACAGCCATCGAGGA CTTATAATGTACTCATGGGATTGTCCTATGGAGCAATGTAAACGTAACTCAACCAGT ATATATTTTAAGATGGAAAATGATCTTCCACAAAAAATACAGTGTACTCTTAGCAAT CCATTATTTAATACAACATCATCAATCATTTTGACAACCTGTATCCCAAGCAGCGGT CATTCAAGACACAGATATGCACTTATACCCATACCATTAGCAGTAATTACAACATGT ATTGTGCTGTATATGAATGGTATTCTGAAATGTGACAGAAAACCAGACAGAACCAAC TCCAATTGATTGGTAACAGAAGATGAAGACAACAGCATAACTAAATTATTTTAAAAA CTAAAAAGCCATCTGATTTCTCATTTGAGTATTACAATTTTTGAACAACTGTTGGAA ATGTAACTTGAAGCAGCTGCTTTAAGAAGAAATACCCACTAACAAAGAACAAGCATT AGTTTTGGCTGTCATCAACTTATTATATGACTAGGTGCTTGCTTTTTTTGTCAGTAA ATTGTTTTTACTGATGATGTAGATACTTTTGTAAATAAATGTAAATATGTACACAAG TGA(SEQIDNO:145) >NP_001770.1lymphocytefunction-associatedantigen3 isoform1[Homosapiens] MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWK KQKDKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTM KFFLYVLESLPSPTLTCALTNGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNST SIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITT CIVLYMNGILKCDRKPDRINSN(SEQIDNO:146) HumanSLAM >NM_003037.5Homosapienssignalinglymphocytic (CD150) activationmoleculefamilymember1(SLAMF1),transcript variant1,mRNA AGACAGCCTCTGCTGCATGACACGAAGCTTGCTTCTGCCTGGCATCTGTGAGCAGCT GCCAGGCTCCGGCCAGGATCCCTTCCTTCTCCTCATTGGCTGATGGATCCCAAGGGG CTCCTCTCCTTGACCTTCGTGCTGTTTCTCTCCCTGGCTTTTGGGGCAAGCTACGGA ACAGGTGGGCGCATGATGAACTGCCCAAAGATTCTCCGGCAGTTGGGAAGCAAAGTG CTGCTGCCCCTGACATATGAAAGGATAAATAAGAGCATGAACAAAAGCATCCACATT GTCGTCACAATGGCAAAATCACTGGAGAACAGTGTCGAGAACAAAATAGTGTCTCTT GATCCATCCGAAGCAGGCCCTCCACGTTATCTAGGAGATCGCTACAAGTTTTATCTG GAGAATCTCACCCTGGGGATACGGGAAAGCAGGAAGGAGGATGAGGGATGGTACCTT ATGACCCTGGAGAAAAATGTTTCAGTTCAGCGCTTTTGCCTGCAGTTGAGGCTTTAT GAGCAGGTCTCCACTCCAGAAATTAAAGTTTTAAACAAGACCCAGGAGAACGGGACC TGCACCTTGATACTGGGCTGCACAGTGGAGAAGGGGGACCATGTGGCTTACAGCTGG AGTGAAAAGGCGGGCACCCACCCACTGAACCCAGCCAACAGCTCCCACCTCCTGTCC CTCACCCTCGGCCCCCAGCATGCTGACAATATCTACATCTGCACCGTGAGCAACCCT ATCAGCAACAATTCCCAGACCTTCAGCCCGTGGCCCGGATGCAGGACAGACCCCTCA GAAACAAAACCATGGGCAGTGTATGCTGGGCTGTTAGGGGGTGTCATCATGATTCTC ATCATGGTGGTAATACTACAGTTGAGAAGAAGAGGTAAAACGAACCATTACCAGACA ACAGTGGAAAAAAAAAGCCTTACGATCTATGCCCAAGTCCAGAAACCAGGTCCTCTT CAGAAGAAACTTGACTCCTTCCCAGCTCAGGACCCTTGCACCACCATATATGTTGCT GCCACAGAGCCTGTCCCAGAGTCTGTCCAGGAAACAAATTCCATCACAGTCTATGCT AGTGTGACACTTCCAGAGAGCTGACACCAGAGACCAACAAAGGGACTTTCTGAAGGA AAATGGAAAAACCAAAATGAACACTGAACTTGGCCACAGGCCCCAAGTTTCCTCTGG CAGACATGCTGCACGTCTGTACCCTTCTCAGATCAACTCCCTGGTGATGTTTCTTCC ACATACATCTGTGAAATGAACAAGGAAGTGAGGCTTCCCAAGAATTTAGCTTGCTGT GCAGTGGCTGCAGGCGCAGAACAGAGCGTTACTTGATAACAGCGTTCCATCTTTGTG TTGTAGCAGATGAAATGGACAGTAATGTGAGTTCAGACTTTGGGCATCTTGCTCTTG GCTGGAACTGGATAATAAAAATCAGACTGAAAGCCAGGACATCTGAGTACCTATCTC ACACACTGGACCACCAGTCACAAAGTCTGGAAAAGTTTACATTTTGGCTATCTTTAC TTTGTTCTGGGAGCTGATCATGATAACCTGCAGACCTGATCAAGCCTCTGTGCCTCA GTTTCTCTCTCAGGATAAAGAGTGAATAGAGGCTGAAGGGTGAATTTCTTATTATAC ATAAAACACTCTGATATTATTGTATAAAGGAAGCTAAGAATATTATTTTATTTGCAA AACCCAGAAGCTAAAAAGTCAATAAACAGAAAGAATGATTTTGAGATCTCTGAGTTT TGAACAGTGGACTGGAAACCATGTAAGAGCCTTAAAAGTACAGTTCTGTGCAAATGG CATTCAGTTTTAAAGAAAAACGTAGCAAATGTTTGATGGTGCTGTTACAAAGGAGCT TGGAATACTCAGAGGAACTTGTCCCATGGTGATTTTTCACTTCTCAAAATGATGTTT AAATCCCAGTTCTCTGTTGATTCCCTTGAACAACAAACCTGGAACCTCAGCTAAGAC TCTCTGTGACCAGATTCTGAACCTCTTATATCCAGGGCTTCAAGGGGTATTGCAGGT CAAGGTCTTTCCTAGGCACTTTCTACTCCCTGCATACCTCTCCTCACACTAAATTTA TCCTCTAGTAGAAAATTAAGTTATTTTGGTCTAACAGCTTCAAATCTTTGAATGCTC AATAACTTATTTTGCAAGCTGCAGGCAGAAAGAGACTTTTTAAGTAAAGTCCTTTGT TTTTTCCTATTCTCTGCTTTTAGACAGGCTGTCCTCAATTTAAGCCCTGCTTTTTCT TATTGTTTCTTATATAAACTTGGTAAGTACTGTAAGAAACAGCCACTATCATACCAT TGCATAATAAGGAGCACCAACTTCCCAGCTCAAAACTCAGGTCCTTATTGCCTTGTA TCTTACCTCCTCTATGAGGTCAATTCACATTGTAAGCCTGTTGCTTAGTGCATCTCG TTTCCTGGTACCAGCTTCTTTAATAGAGTTCTTAGTTGCAATCAACAGAAGCTGGCT TTGGCTTTTTTATGTAGAAAAGGAACCTATTGAAAAGATACTGATTGGTTCCAATAA CTGCTAGAAGTTTCTGCAAAACCATGCTTTGAAAGTGAGCAGGAAAAGAAGAGACTA GGCTGTGGCTGGGAGCACAGCCAAAATTACAAAACCAGCCCAGGGATGATGATCCTG TTCATGCACAGCCACTGTCCCCAGCACTAGGCACAGACTCTACCACTGCCTCACTGT CTCTGCTGGACTTGGAAACTTGATATTACTGTTACTGCTGCACTGTCTGCCATGAAA ATGAATTCTCCAGGGTCCCTTCTTCATCCTTTCATCTCTAGCTTATAATTCAAAGTC TGGGATTGAGTGGCCAATCCTAGGTCACATGTCCATGTCCTATCTCCAAGGGGGGCT GGGAATTGAATATCTGGCATTTTCCACTTTCACTTCTTATGAATTAAGGAATTCTAC AAATAATAGAAGTGGGATTCAGGTGGTAGGCAGACAAAAAAGCCTCACAATTATCCA CTACGCCACCCTTGTATAACCTTACCCTCATTCACTGTCTACTCTCAAAACTGTGGA GCTACTAATGAAGATTTGTAAACCCGGGCTTATGAGCACCCATTCCTTTACTACAAC TCAGATTGCTCTAGAAGCTCAGTTCCCAGCACTTGGATTTTTCCAGTAGCTGAATTC TACCTGAAGGAAGGGCAGAAACAAAGGGTGAAGAAGAGGCTATCACTTCCAAGTATC CTGCACCCCTGGGCTCAAGACCTCACTGGGGAGGGAGTCTTTTGGGCCACCCACCAA ACAGCACTGGCATTATGCCTCTCACCCTAGACCATGGTTACACGTGGTAAAACAACC CCTTCTGGTGATACATTCACAACTCTCTAGTTTCCCCCAAATGGCACTATGGGGAGC GGGAGCTTGCCTTTTCCTCAGACTTAAAACAATAAGTTTTCCCCGTGTTTCCCCTCT AATGCTGTTTTCTTTTGACCAAGCATGTCTGAATTCTAGAGAAGTCAGGAGGAACAC ACCCATTCTCGGTTTGAAGGGACTGATGTTCTGAAGTACAACTGGGCACAGTCCCAG GCTCTTCAGGACGCTTCCTCCATTCACACAGCGGGGATGTGATTGTTACAGCGGGTG GTGTGTGCTGGCTGAGAAGCCACTGTGAATTGATTCTTCTTCTGAAGTTTATGTTTC TACTTTTTGGAAATGAATAAATTACAGCCAGTCCATCAAGGAAA(SEQIDNO: 147) >NP_003028.1signalinglymphocyticactivationmolecule isoformbprecursor[Homosapiens] MDPKGLLSLTFVLFLSLAFGASYGTGGRMMNCPKILRQLGSKVLLPLTYERINKSMN KSIHIVVTMAKSLENSVENKIVSLDPSEAGPPRYLGDRYKFYLENLTLGIRESRKED EGWYLMTLEKNVSVQRFCLQLRLYEQVSTPEIKVLNKTQENGTCTLILGCTVEKGDH VAYSWSEKAGTHPLNPANSSHLLSLTLGPQHADNIYICTVSNPISNNSQTFSPWPGC RTDPSETKPWAVYAGLLGGVIMILIMVVILQLRRRGKTNHYQTTVEKKSLTIYAQVQ KPGPLQKKLDSFPAQDPCTTIYVAATEPVPESVQETNSITVYASVTLPES(SEQ IDNO:148) MouseSLAM >NM_013730.4Musmusculussignalinglymphocytic (CD150) activationmoleculefamilymember1(Slamf1),transcript variant1,mRNA GAGCTTCTTCCTTGGGGGTAACAGTAAGCAGCTGTCCTGCCGAGCTGAGCTGAGCTG AGCTCACAGCTGGGGACCCTGTCTGCGATTGCTGGCTAATGGATCCCAAAGGATCCC TTTCCTGGAGAATACTTCTGTTTCTCTCCCTGGCTTTTGAGTTGAGCTACGGAACAG GTGGAGGTGTGATGGATTGCCCAGTGATTCTCCAGAAGCTGGGACAGGACACGTGGC TGCCCCTGACGAATGAACATCAGATAAATAAGAGCGTGAACAAAAGTGTCCGCATCC TCGTCACCATGGCGACGTCCCCAGGAAGCAAATCCAACAAGAAAATTGTGTCTTTTG ATCTCTCTAAAGGGAGCTATCCAGATCACCTGGAGGATGGCTACCACTTTCAATCAA AAAACCTGAGCCTGAAGATCCTCGGGAACAGGCGGGAGAGTGAAGGATGGTACTTGG TGAGCGTGGAGGAGAACGTTTCTGTTCAGCAATTCTGCAAGCAGCTGAAGCTTTATG AACAGGTCTCCCCTCCAGAGATTAAAGTGCTAAACAAAACCCAGGAGAACGAGAATG GGACCTGCAGCTTGCTGTTGGCCTGCACAGTGAAGAAAGGGGACCATGTGACTTACA GCTGGAGTGATGAGGCAGGCACCCACCTGCTGAGCCGAGCCAACCGCTCCCACCTCC TGCACATCACTCTTAGCAACCAGCATCAAGACAGCATCTACAACTGCACCGCAAGCA ACCCTGTCAGCAGTATCTCTAGGACCTTCAACCTATCATCGCAAGCATGCAAGCAGG AATCCTCCTCAGAATCGAGTCCATGGATGCAATATACTCTTGTACCACTGGGGGTCG TTATAATCTTCATCCTGGTTTTCACGGCAATAATAATGATGAAAAGACAAGGTAAAT CAAATCACTGCCAGCCACCAGTGGAAGAAAAAAGCCTTACTATTTATGCCCAAGTAC AGAAATCAGGGCCTCAAGAGAAGAAACTTCATGATGCCCTAACAGATCAGGACCCCT GCACAACCATTTATGTGGCTGCCACAGAGCCTGCCCCAGAGTCTGTCCAGGAACCAA ACCCCACCACAGTTTATGCCAGTGTGACACTGCCAGAGAGCTGACCCATATACCCAG TGAAAGGACTTTTTGAAGGAGGATAGAAGAACCAAAATCCACACTGAACTGGACCCC GGGTCCCAAGTTCTCTGTGACAGAAACTGCACATCTGTAACCTTCTCCAATCAGTTC CCTGGTGACGGATCTGCACAGGCGTGCTTATGAAGTAGATGAGAAGTGAGGCTTCCT GGGCATGCAACCTGCTCTGCTGCTGACACAGATATGAAGCAGAGATCCCGTGGTACA GTGTACCATCTTTGCTGTAGCAGATAATGTGGGTTTAGGCATCTCACTCTTTGCTGG ACTGGATAACAGAACTCAAAAAAAAACCAACAAGCCAAAGACATAGACTCCATCTCA GATGGCTGAGCACAAAGTATAAAAGCCATTTTGGCTCTCTGGACTTTATTCTGGAAG CTGATCCTGATCACCTCAAGGCCAAGGGCTCCATGCCTCAGTTTCTCTCTCACCCTC TAGATGAAGAGGGAACAAAGCATAAAGAGTGAAATCCTTGTTGTCTGAGATCATTCT ATAAACGAACTGACATTTTATTTGCAAAACTCAAGCTAGTAATTCAGTAGACTTGAA GATGATTTTAGAGCCTCTTATGCTTCAAACAACAGAATGAAATCCATCCAATGTTCT TCAAAGTGTGGTTCTCTGATTAAGTCAAAGCAACACTGTTTGGCAATGCTGCTGTAA AGTTGCCTGGAATACTCAGAGGAACTTGTCCCAGGGAGGTTTTTTTCACTTCTTCAA AGAACTTTTGAATTTAAGTTCTCTGTTTATTCCCTTGAGCAAAACTCTGGAACCTCA AGAGTCTCTCTCCGTTGGTTCTGAGGCCATTTTATAGCCTAGGCCTCCTGTGGATCT ACATGTGTATCACCCACTTCCTATCTCACTGCATACCTCTGTGTAGTAGTAAATTTA ACCTCAAGTAGAAAATTAAATTATTTTGGATGATCAGTTCCAAATGATTAGATGTTT AGTCTCTTATAATAGGATGTAGGTAGAGTCTATATAAAGTCCTATATTCTTCACGTT GTCTGTCCTCAGAGAGACCATCTTTCAACCTATCTTCCTTCTTGCACAACTTTGGCA AATACTTTAAAAATAACCATTGTGGAGATGGGGAGAGGTCTAAATGGATAATAGTAC TTGCTTTGCAAACATGAAGATCTGGGTTCAAACTCCCAGTGTCCATGTAAAAAGATA AGTGTGGTTGAGTGTGCCAGTAACATAGACACAGATAGGTCCTGAGACTTTGCTCCC TAGCCTTCCCAGCCAGGCATAAATGTCAAGTCCCCTGAGAGTGACAGAGGAAGATAC TCCCCCCACACACACACACATACACGCACAGTGATACACATATACATGCATACAAAA AAAAAACTTATTGTAACAAAGAACACCAACTGCCTGGCTCAAAACTCTCATGTCCCA TTACTCTGTACCTTTCTGTATTTAGATAATTTACAGTGTGAGTTCTGCTGTTCCATG TATCCTATTTGTGTTACTAACTTATGTCAAAGTATTTCTAATTATAATCAACAAAAG CTAACTTTG(SEQIDNO:149) >NP_038758.2signalinglymphocyticactivationmolecule isoform1precursor[Musmusculus] MDPKGSLSWRILLFLSLAFELSYGTGGGVMDCPVILQKLGQDTWLPLTNEHQINKSV NKSVRILVTMATSPGSKSNKKIVSFDLSKGSYPDHLEDGYHFQSKNLSLKILGNRRE SEGWYLVSVEENVSVQQFCKQLKLYEQVSPPEIKVLNKTQENENGTCSLLLACTVKK GDHVTYSWSDEAGTHLLSRANRSHLLHITLSNQHQDSIYNCTASNPVSSISRTFNLS SQACKQESSSESSPWMQYTLVPLGVVIIFILVFTAIIMMKRQGKSNHCQPPVEEKSL TIYAQVQKSGPQEKKLHDALTDQDPCTTIYVAATEPAPESVQEPNPTTVYASVTLPE S(SEQIDNO:150) HumanCD40 >NM_001250.6HomosapiensCD40molecule(CD40), transcriptvariant1,mRNA AGTGGTCCTGCCGCCTGGTCTCACCTCGCTATGGTTCGTCTGCCTCTGCAGTGCGTC CTCTGGGGCTGCTTGCTGACCGCTGTCCATCCAGAACCACCCACTGCATGCAGAGAA AAACAGTACCTAATAAACAGTCAGTGCTGTTCTTTGTGCCAGCCAGGACAGAAACTG GTGAGTGACTGCACAGAGTTCACTGAAACGGAATGCCTTCCTTGCGGTGAAAGCGAA TTCCTAGACACCTGGAACAGAGAGACACACTGCCACCAGCACAAATACTGCGACCCC AACCTAGGGCTTCGGGTCCAGCAGAAGGGCACCTCAGAAACAGACACCATCTGCACC TGTGAAGAAGGCTGGCACTGTACGAGTGAGGCCTGTGAGAGCTGTGTCCTGCACCGC TCATGCTCGCCCGGCTTTGGGGTCAAGCAGATTGCTACAGGGGTTTCTGATACCATC TGCGAGCCCTGCCCAGTCGGCTTCTTCTCCAATGTGTCATCTGCTTTCGAAAAATGT CACCCTTGGACAAGCTGTGAGACCAAAGACCTGGTTGTGCAACAGGCAGGCACAAAC AAGACTGATGTTGTCTGTGGTCCCCAGGATCGGCTGAGAGCCCTGGTGGTGATCCCC ATCATCTTCGGGATCCTGTTTGCCATCCTCTTGGTGCTGGTCTTTATCAAAAAGGTG GCCAAGAAGCCAACCAATAAGGCCCCCCACCCCAAGCAGGAACCCCAGGAGATCAAT TTTCCCGACGATCTTCCTGGCTCCAACACTGCTGCTCCAGTGCAGGAGACTTTACAT GGATGCCAACCGGTCACCCAGGAGGATGGCAAAGAGAGTCGCATCTCAGTGCAGGAG AGACAGTGAGGCTGCACCCACCCAGGAGTGTGGCCACGTGGGCAAACAGGCAGTTGG CCAGAGAGCCTGGTGCTGCTGCTGCTGTGGCGTGAGGGTGAGGGGCTGGCACTGACT GGGCATAGCTCCCCGCTTCTGCCTGCACCCCTGCAGTTTGAGACAGGAGACCTGGCA CTGGATGCAGAAACAGTTCACCTTGAAGAACCTCTCACTTCACCCTGGAGCCCATCC AGTCTCCCAACTTGTATTAAAGACAGAGGCAGAAGTTTGGTGGTGGTGGTGTTGGGG TATGGTTTAGTAATATCCACCAGACCTTCCGATCCAGCAGTTTGGTGCCCAGAGAGG CATCATGGTGGCTTCCCTGCGCCCAGGAAGCCATATACACAGATGCCCATTGCAGCA TTGTTTGTGATAGTGAACAACTGGAAGCTGCTTAACTGTCCATCAGCAGGAGACTGG CTAAATAAAATTAGAATATATTTATACAACAGAATCTCAAAAACACTGTTGAGTAAG GAAAAAAAGGCATGCTGCTGAATGATGGGTATGGAACTTTTTAAAAAAGTACATGCT TTTATGTATGTATATTGCCTATGGATATATGTATAAATACAATATGCATCATATATT GATATAACAAGGGTTCTGGAAGGGTACACAGAAAACCCACAGCTCGAAGAGTGGTGA CGTCTGGGGTGGGGAAGAAGGGTCTGGGGGAGGGTTGGTTAAAGGGAGATTTGGCTT TCCCATAATGCTTCATCATTTTTCCCAAAAGGAGAGTGAATTCACATAATGCTTATG TAATTAAAAAATCATCAAACATGTAAAAA(SEQIDNO:151) >NP_001241.1tumornecrosisfactorreceptorsuperfamily member5isoform1precursor[Homosapiens] MVRLPLQCVLWGCLLTAVHPEPPTACREKQYLINSQCCSLCQPGQKLVSDCTEFTET ECLPCGESEFLDTWNRETHCHQHKYCDPNLGLRVQQKGTSETDTICTCEEGWHCTSE ACESCVLHRSCSPGFGVKQIATGVSDTICEPCPVGFFSNVSSAFEKCHPWTSCETKD LVVQQAGTNKTDVVCGPQDRLRALVVIPIIFGILFAILLVLVFIKKVAKKPTNKAPH PKQEPQEINFPDDLPGSNTAAPVQETLHGCQPVTQEDGKESRISVQERQ(SEQID NO:152) MouseCD40 >NM_170703.2MusmusculusCD40antigen(Cd40),transcript variant2,mRNA AGCAGGGACTTTGGAGTGACTTGTGGCTTCAGCAGGAGCCCTGTGATTTGGCTCTTC TGATCTCGCCCTGCGATGGTGTCTTTGCCTCGGCTGTGCGCGCTATGGGGCTGCTTG TTGACAGCGGTCCATCTAGGGCAGTGTGTTACGTGCAGTGACAAACAGTACCTCCAC GATGGCCAGTGCTGTGATTTGTGCCAGCCAGGAAGCCGACTGACAAGCCACTGCACA GCTCTTGAGAAGACCCAATGCCACCCATGTGACTCAGGCGAATTCTCAGCCCAGTGG AACAGGGAGATTCGCTGTCACCAGCACAGACACTGTGAACCCAATCAAGGGCTTCGG GTTAAGAAGGAGGGCACCGCAGAATCAGACACTGTCTGTACCTGTAAGGAAGGACAA CACTGCACCAGCAAGGATTGCGAGGCATGTGCTCAGCACACGCCCTGTATCCCTGGC TTTGGAGTTATGGAGATGGCCACTGAGACCACTGATACCGTCTGTCATCCCTGCCCA GTCGGCTTCTTCTCCAATCAGTCATCACTTTTCGAAAAGTGTTATCCCTGGACAAGG TTTAAAGTCCCGGATGCGAGCCCTGCTGGTCATTCCTGTCGTGATGGGCATCCTCAT CACCATTTTCGGGGTGTTTCTCTATATCAAAAAGGTGGTCAAGAAACCAAAGGATAA TGAGATCTTACCCCCTGCGGCTCGACGGCAAGATCCCCAGGAGATGGAAGATTATCC CGGTCATAACACCGCTGCTCCAGTGCAGGAGACGCTGCACGGGTGTCAGCCTGTCAC ACAGGAGGATGGTAAAGAGAGTCGCATCTCAGTGCAGGAGCGGCAGGTGACAGACAG CATAGCCTTGAGGCCCCTGGTCTGAACCCTGGAACTGCTTTGGAGGCGATGGCTCGG CTCGGGAGCAGGGGCCTGGCTCTGAGGACTGCTTGCTGACCTTTGAAGTTTGAGATG AGCCAAGACAGAGCCCAGTGCAGCTAACTCTCATGCCTGCCCCCTATCATTTCTCAA CTTGCTTTTTAAGGATGGAGGGAGAGCTCGGGCATCGGGGGTCCACAGTGATACCTA CCAAGTGCAGCAGTGCAGGACCCAGAGTCGTCTTGCTGCGGCGTTCACTGTAAGGAG TCATGGACACAGGAGTCCGTGGCCCACAGCTTGTGCTGCTAGAGGGCACCTGGTTGC CCATCAGCAGGGTACTGGCTAAATAAATCTGTAATTATTTATACAATGACATCTCAG AAACTCTAGCAGGTGGGGCAGAAAACAGGTAGTAGAATGATGGGTAGAGAAATAGCT TTTAAAACACATTCCAAGGCAGGTAAGATGGCTTTTGTGAGTAAAGGAGCTTGCTGC CCAAACCCGGTTACCTGATTTTGATCCCTGGGACTTCATGGTAAAAGGGAGAGAACC AAATCCAGAGGGTTGTCATTTGACCTCCATGTGTGCTCTGTGGTAATGTACCCCGTG TGTGCACATGTGCACATATCCTAAAATGGATGTGGTGGTGTATTGTAGAAATTATTT AATCCCGCCCTGGGGTTTCTACCTGTGTGTTACCATTTAGTTCTTGAATAAAAGACA CACTCAACCTTTATATTTACAATAA(SEQIDNO:153) >NP_733804.1tumornecrosisfactorreceptorsuperfamily member5isoform2precursor[Musmusculus] MVSLPRLCALWGCLLTAVHLGQCVTCSDKQYLHDGQCCDLCQPGSRLTSHCTALEKT QCHPCDSGEFSAQWNREIRCHQHRHCEPNQGLRVKKEGTAESDTVCTCKEGQHCTSK DCEACAQHTPCIPGFGVMEMATETTDTVCHPCPVGFFSNQSSLFEKCYPWTRFKVPD ASPAGHSCRDGHPHHHFRGVSLYQKGGQETKG(SEQIDNO:154) HumanCD28 >NM_006139.4HomosapiensCD28molecule(CD28), transcriptvariant1,mRNA ACACTTCGGGTTCCTCGGGGAGGAGGGGCTGGAACCCTAGCCCATCGTCAGGACAAA GATGCTCAGGCTGCTCTTGGCTCTCAACTTATTCCCTTCAATTCAAGTAACAGGAAA CAAGATTTTGGTGAAGCAGTCGCCCATGCTTGTAGCGTACGACAATGCGGTCAACCT TAGCTGCAAGTATTCCTACAATCTCTTCTCAAGGGAGTTCCGGGCATCCCTTCACAA AGGACTGGATAGTGCTGTGGAAGTCTGTGTTGTATATGGGAATTACTCCCAGCAGCT TCAGGTTTACTCAAAAACGGGGTTCAACTGTGATGGGAAATTGGGCAATGAATCAGT GACATTCTACCTCCAGAATTTGTATGTTAACCAAACAGATATTTACTTCTGCAAAAT TGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTAT CCATGTGAAAGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCC CTTTTGGGTGCTGGTGGTGGTTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAAC AGTGGCCTTTATTATTTTCTGGGTGAGGAGTAAGAGGAGCAGGCTCCTGCACAGTGA CTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAAGCATTACCAGCCCTA TGCCCCACCACGCGACTTCGCAGCCTATCGCTCCTGACACGGACGCCTATCCAGAAG CCAGCCGGCTGGCAGCCCCCATCTGCTCAATATCACTGCTCTGGATAGGAAATGACC GCCATCTCCAGCCGGCCACCTCAGGCCCCTGTTGGGCCACCAATGCCAATTTTTCTC GAGTGACTAGACCAAATATCAAGATCATTTTGAGACTCTGAAATGAAGTAAAAGAGA TTTCCTGTGACAGGCCAAGTCTTACAGTGCCATGGCCCACATTCCAACTTACCATGT ACTTAGTGACTTGACTGAGAAGTTAGGGTAGAAAACAAAAAGGGAGTGGATTCTGGG AGCCTCTTCCCTTTCTCACTCACCTGCACATCTCAGTCAAGCAAAGTGTGGTATCCA CAGACATTTTAGTTGCAGAAGAAAGGCTAGGAAATCATTCCTTTTGGTTAAATGGGT GTTTAATCTTTTGGTTAGTGGGTTAAACGGGGTAAGTTAGAGTAGGGGGAGGGATAG GAAGACATATTTAAAAACCATTAAAACACTGTCTCCCACTCATGAAATGAGCCACGT AGTTCCTATTTAATGCTGTTTTCCTTTAGTTTAGAAATACATAGACATTGTCTTTTA TGAATTCTGATCATATTTAGTCATTTTGACCAAATGAGGGATTTGGTCAAATGAGGG ATTCCCTCAAAGCAATATCAGGTAAACCAAGTTGCTTTCCTCACTCCCTGTCATGAG ACTTCAGTGTTAATGTTCACAATATACTTTCGAAAGAATAAAATAGTTCTCCTACAT GAAGAAAGAATATGTCAGGAAATAAGGTCACTTTATGTCAAAATTATTTGAGTACTA TGGGACCTGGCGCAGTGGCTCATGCTTGTAATCCCAGCACTTTGGGAGGCCGAGGTG GGCAGATCACTTGAGATCAGGACCAGCCTGGTCAAGATGGTGAAACTCCGTCTGTAC TAAAAATACAAAATTTAGCTTGGCCTGGTGGCAGGCACCTGTAATCCCAGCTGCCCA AGAGGCTGAGGCATGAGAATCGCTTGAACCTGGCAGGCGGAGGTTGCAGTGAGCCGA GATAGTGCCACAGCTCTCCAGCCTGGGCGACAGAGTGAGACTCCATCTCAAACAACA ACAACAACAACAACAACAACAACAAACCACAAAATTATTTGAGTACTGTGAAGGATT ATTTGTCTAACAGTTCATTCCAATCAGACCAGGTAGGAGCTTTCCTGTTTCATATGT TTCAGGGTTGCACAGTTGGTCTCTTTAATGTCGGTGTGGAGATCCAAAGTGGGTTGT GGAAAGAGCGTCCATAGGAGAAGTGAGAATACTGTGAAAAAGGGATGTTAGCATTCA TTAGAGTATGAGGATGAGTCCCAAGAAGGTTCTTTGGAAGGAGGACGAATAGAATGG AGTAATGAAATTCTTGCCATGTGCTGAGGAGATAGCCAGCATTAGGTGACAATCTTC CAGAAGTGGTCAGGCAGAAGGTGCCCTGGTGAGAGCTCCTTTACAGGGACTTTATGT GGTTTAGGGCTCAGAGCTCCAAAACTCTGGGCTCAGCTGCTCCTGTACCTTGGAGGT CCATTCACATGGGAAAGTATTTTGGAATGTGTCTTTTGAAGAGAGCATCAGAGTTCT TAAGGGACTGGGTAAGGCCTGACCCTGAAATGACCATGGATATTTTTCTACCTACAG TTTGAGTCAACTAGAATATGCCTGGGGACCTTGAAGAATGGCCCTTCAGTGGCCCTC ACCATTTGTTCATGCTTCAGTTAATTCAGGTGTTGAAGGAGCTTAGGTTTTAGAGGC ACGTAGACTTGGTTCAAGTCTCGTTAGTAGTTGAATAGCCTCAGGCAAGTCACTGCC CACCTAAGATGATGGTTCTTCAACTATAAAATGGAGATAATGGTTACAAATGTCTCT TCCTATAGTATAATCTCCATAAGGGCATGGCCCAAGTCTGTCTTTGACTCTGCCTAT CCCTGACATTTAGTAGCATGCCCGACATACAATGTTAGCTATTGGTATTATTGCCAT ATAGATAAATTATGTATAAAAATTAAACTGGGCAATAGCCTAAGAAGGGGGGAATAT TGTAACACAAATTTAAACCCACTACGCAGGGATGAGGTGCTATAATATGAGGACCTT TTAACTTCCATCATTTTCCTGTTTCTTGAAATAGTTTATCTTGTAATGAAATATAAG GCACCTCCCACTTTTATGTATAGAAAGAGGTCTTTTAATTTTTTTTTAATGTGAGAA GGAAGGGAGGAGTAGGAATCTTGAGATTCCAGATCGAAAATACTGTACTTTGGTTGA TTTTTAAGTGGGCTTCCATTCCATGGATTTAATCAGTCCCAAGAAGATCAAACTCAG CAGTACTTGGGTGCTGAAGAACTGTTGGATTTACCCTGGCACGTGTGCCACTTGCCA GCTTCTTGGGCACACAGAGTTCTTCAATCCAAGTTATCAGATTGTATTTGAAAATGA CAGAGCTGGAGAGTTTTTTGAAATGGCAGTGGCAAATAAATAAATACTTTTTTTTAA ATGGAAAGACTTGATCTATGGTAATAAATGATTTTGTTTTCTGACTGGAAAAATAGG CCTACTAAAGATGAATCACACTTGAGATGTTTCTTACTCACTCTGCACAGAAACAAA GAAGAAATGTTATACAGGGAAGTCCGTTTTCACTATTAGTATGAACCAAGAAATGGT TCAAAAACAGTGGTAGGAGCAATGCTTTCATAGTTTCAGATATGGTAGTTATGAAGA AAACAATGTCATTTGCTGCTATTATTGTAAGAGTCTTATAATTAATGGTACTCCTAT AATTTTTGATTGTGAGCTCACCTATTTGGGTTAAGCATGCCAATTTAAAGAGACCAA GTGTATGTACATTATGTTCTACATATTCAGTGATAAAATTACTAAACTACTATATGT CTGCTTTAAATTTGTACTTTAATATTGTCTTTTGGTATTAAGAAAGATATGCTTTCA GAATAGATATGCTTCGCTTTGGCAAGGAATTTGGATAGAACTTGCTATTTAAAAGAG GTGTGGGGTAAATCCTTGTATAAATCTCCAGTTTAGCCTTTTTTGAAAAAGCTAGAC TTTCAAATACTAATTTCACTTCAAGCAGGGTACGTTTCTGGTTTGTTTGCTTGACTT CAGTCACAATTTCTTATCAGACCAATGGCTGACCTCTTTGAGATGTCAGGCTAGGCT TACCTATGTGTTCTGTGTCATGTGAATGCTGAGAAGTTTGACAGAGATCCAACTTCA GCCTTGACCCCATCAGTCCCTCGGGTTAACTAACTGAGCCACCGGTCCTCATGGCTA TTTTAATGAGGGTATTGATGGTTAAATGCATGTCTGATCCCTTATCCCAGCCATTTG CACTGCCAGCTGGGAACTATACCAGACCTGGATACTGATCCCAAAGTGTTAAATTCA ACTACATGCTGGAGATTAGAGATGGTGCCAATAAAGGACCCAGAACCAGGATCTTGA TTGCTATAGACTTATTAATAATCCAGGTCAAAGAGAGTGACACACACTCTCTCAAGA CCTGGGGTGAGGGAGTCTGTGTTATCTGCAAGGCCATTTGAGGCTCAGAAAGTCTCT CTTTCCTATAGATATATGCATACTTTCTGACATATAGGAATGTATCAGGAATACTCA ACCATCACAGGCATGTTCCTACCTCAGGGCCTTTACATGTCCTGTTTACTCTGTCTA GAATGTCCTTCTGTAGATGACCTGGCTTGCCTCGTCACCCTTCAGGTCCTTGCTCAA GTGTCATCTTCTCCCCTAGTTAAACTACCCCACACCCTGTCTGCTTTCCTTGCTTAT TTTTCTCCATAGCATTTTACCATCTCTTACATTAGACATTTTTCTTATTTATTTGTA GTTTATAAGCTTCATGAGGCAAGTAACTTTGCTTTGTTTCTTGCTGTATCTCCAGTG CCCAGAGCAGTGCCTGGTATATAATAAATATTTATTGACTGAGTGAA(SEQID NO:155) >NP_006130.1T-cell-specificsurfaceglycoproteinCD28 isoform1precursor[Homosapiens] MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSCKYSYNLFSREFRASLHK GLDSAVEVCVVYGNYSQQLQVYSKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKI EVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVT VAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS(SEQID NO:156) MouseCD28 >NM_007642.4MusmusculusCD28antigen(Cd28),mRNA AGACCTTGGCAGATGTGACTTCAGTTCACACCACACTCTGCCTTGCTCACAGAGGAG GGGCTGCAGCCCTGGCCCTCATCAGAACAATGACACTCAGGCTGCTGTTCTTGGCTC TCAACTTCTTCTCAGTTCAAGTAACAGAAAACAAGATTTTGGTAAAGCAGTCGCCCC TGCTTGTGGTAGATAGCAACGAGGTCAGCCTCAGCTGCAGGTATTCCTACAACCTTC TCGCAAAGGAATTCCGGGCATCCCTGTACAAGGGCGTGAACAGCGACGTGGAAGTCT GTGTCGGGAATGGGAATTTTACCTATCAGCCCCAGTTTCGCTCGAATGCCGAGTTCA ACTGCGACGGGGATTTCGACAACGAAACAGTGACGTTCCGTCTCTGGAATCTGCACG TCAATCACACAGATATTTACTTCTGCAAAATTGAGTTCATGTACCCTCCGCCTTACC TAGACAACGAGAGGAGCAATGGAACTATTATTCACATAAAAGAGAAACATCTTTGTC ATACTCAGTCATCTCCTAAGCTGTTTTGGGCACTGGTCGTGGTTGCTGGAGTCCTGT TTTGTTATGGCTTGCTAGTGACAGTGGCTCTTTGTGTTATCTGGACAAATAGTAGAA GGAACAGACTCCTTCAAAGTGACTACATGAACATGACTCCCCGGAGGCCTGGGCTCA CTCGAAAGCCTTACCAGCCCTACGCCCCTGCCAGAGACTTTGCAGCGTACCGCCCCT GACAGGGACCCCTATCCAGAAGCCCGCCGGCTGGTACCCGTCTACCTGCTCATCATC ACTGCTCTGGATAGGAAAGGACAGCCTCATCTTCAGCCGGCCACTTTGGACCTCTAC TGGGCCACCAATGCCAACTATTTTAGAGTGTCTAGATCTAACATCATGATCATCTTG AGACTCTGGAATGAATGACAGAAGCTTCTATGGCAGGATAAAGTCTGTGTGGCTTGA CCCAAACTCAAGCTTAATACATTTATTGACTTGATTGGGGAAGTTAGAGTAGAGCAA TCAAAAAGATCATTCATTCAGCCTTGGGAAGTCAATTTGCAGGCTCCTGGATGAGCC CTGCCCCGTTTTCACTTGCCAGCACATTTCAGTCATGTGGTGTGATAGCCAAAGATG TTTTGGACAGAGAAGAAAGGATAGAAAAACCTTCTCTTTGGCTAAGTTGGTGTTTGG GGTGGGGATAGGTTAGAGTATAGTACTTAACTATTTGAAAAATAATGAAAACACTTT TTTCACTCATGAAATGAGCCACTTAGCTCCTAAATAGTGTTTTCCTGTTAGTTTAGA AAGTTGTGGACATATTTTTTTAATGATTTCTGACCATTTTTAATCACATTGACTCAT GGAATGGCCTCAAAGCACCCCCCAGTGCTTCTTTCCTCATTCCCGGTCATGGGAACT CAGTATTATTAATAGTCACAACATGATTTCAGAACTAGATAGCCCTCCCACACCAAG AAGAATGTGAGAGGAAGTAAGGTCACTTTATGTAAAAAAAAAAAAAAACAAACGCGT ACACATATGTATGTATACATACATACCTATGTGCACACACACACACATATACATACA CACAAAATGCTATGAAGAGTTATCTGTTTAGTAGCCTGTTATAGTCAAATCATTTTA AGTTTCAACTTCTTACAGTTGGGCCACTTGTTGTCCTTTGTGGATGGATATCTGAAA TTGTGTCTATATATTGCTAGTCATGATACTGTGAACAAAAAGGGTAGTGTTAGTATT TGTCAGGGTGGTAAGGATGCATTCCAGGAAGCTTCCTCTGAGGAAGGGAATGAGGTC ATTCTTGCCATGTATGAAAGACATAGATGTTTTCCAGAAGGCACCATTGGGAGCCCC AGTATAAGTTCCTTTAGACTCTACAGTTTAGAGGGATTTTATATGTCCTAGGACTCA GGACTCCAGAACTTTGTGGGCTCAGCTGCTTCATACCATGGGGATACATTGACATGA ACAATTATTTTGGAATGTGTCTTTAGGGACGACATCAAAGTTCTCAAGTACCTACAA GACCTGATACTGGAATGAAGGTGGACTTTCTTTTTTGCTTCCAGTTCGGATCAACTG GAATGTATCTGGGGACCTTGAAGAACGGCTGTCCAGCTGTCTTCACCATTTGTATAG TGCTTTGAATTATTCAGAGGTTTTAAAGTCAGGAAGACCTGGTTTAAAAAACATTTC ATTATGAGTTAAATGGCCTCAGGCAAGTCACTGTTCATCCAAGTCTATGACTCCTCA ACTGTAAGATGGCCACACTGAAACTTGCTAAGATCCTCTGGCCTCTGCCTCCCAAGA GTTGGGATTTCAGGAGTGCACAATCATGACCCAAACTCGTGATAATCTCTCAGCTTC AATAACTTTCCAGCTAATTGGAATATCCTGTAATCAAACATGAGGCATTTCCCCTCC CCCCACTGTTTTTGTGTATAAAGAGATCTTTAAACTTTTTTTTTAATATGAGGGGTA AGAAAAGATAGGAATCTTTTAATTCTAGACAGAAGATATTGTGCTTTGGTTTTTTTT TTTTTTAATGGCTTCTATTCTGTGCTTTTAATTAAACCAGAGAAGGCCAAGATTAGC CCTACTTGTGTGATAAAAGAATGCTGGCCCTTGTGATTGCAGTCAGCCTCTTGACAC ATAGAGTTCTTGAATCTAAGTTATAAAATTATATTTGAAAATGACAGAGCTGGAGAA TTTATAGAAAGGGTCATAGCAAATAACAAACCATTTTTTTTTAAACGGAAAGATTTG GTCTTTGGCAATCAATAACTTTGTTTTCTAACTGGAAAAGGAGGTTTACTGGAGATG AATCACACCTGAAAGTTTTCATACCTCCTCTGAACACAACCGAAACATAGGTGTCCA AAGCCTTTCGCTCTCGGTATGAACCAACAGGCGGGTTAAAAACACTGGGTCAGAGTA AAGCTTTTGCAGTTTCAGATGTAGTGTGTATGAAGAAAACTATGTCACTTGCTGCTA TTATTGTAAGAGTCTAAGAACTAAAGGTGTGCCTGTAATTTCTAATTATGAGCTCAC CTATTTGGTACCGAGCATGCCAATTTTAAAGAGACCCGGTGTACCTTATAGCTACAT CCAATGATAAAATTACCACACTAGCACATGCCTGTGTTTAAACTCGTGCTTTAATGT TTTTCTTAGGGCAGGTATGCACCCCCTTTGCAGTGAGTTGGGAGAGATTTTGAAAAA GTGTATGACAAACATTTTTAACACCTTTGGTTTCCTCTCTCTGTGTCTCTTTGTCTC TGTCTCTCTCTTTCTCTCCTGTGCATATGTCTCCCCTCCCTCACTTCTCTGTCTCTT CCTCTCTCCCTCTCTCTGTCTTTCTCTGTGTGTCTCTCTGTCTCTGTGTATCTCTCT GTCTGTCTCTTTCTCTGCAGATTTTCAAAACGTTGTTTTTCTATGGAAGAAATACAA GCTGTGGTTGGTTTGCTACGAGTCAGTAGCAGTTTATCAGTAGGCCAATGTTTTATC TCTTGGAGATTTCAGTCTGGGTTTACCCAATGTATTCTCTGTAATGTGACTGCTGGG GACAGATATAACTTGATTGAGCCTTCAAATCATTTAGGTCTTCAATCATTTAGTCAA CGGAGTGAGCCACTAATCTGCAATGGCTATTTTAATATGCATACTGATGGTCAAATG GATGTCTGATCTCTCATCCCAGCTTTCTGTACTACCATATGGGAACTATATGTAACT TGTATACTTACCTGAATATGTTAAATTCAACTACATGGTAAGATGGACCAGAAATTG CAATGTTCATGTCCATATAGCCACCATTAACCCAAGTTAAGCACAGTAGTGTGGGTT CTCTCAGGACTTGTGAATGAGTTTATGCTCTCTACAAAGACAGGTGAAGCTTAAATC TCTCTTGCACTGCTATGTTTATGCAAATATCAAGATTGTTTCTGTACCAGGGACTTA ACACATTCTATTCATACTATTTTCCCTGTCTACAATGTTATTTCATAGATATCTACT TGGTTTGCTCTTACTTCCTTGACATATTTGCCCAAATGCCACCTTCAACTGTAGTTA ATTACCTGTACAACCTGTCTCCATGCCTTGTTTTATTTTCTCTATAACTCTACTAAT AGGTATTTTTCTTATTTATTGGTTTATTGCCTGTTTTTTTTCCTAAATCTACACCGG ATCTCCAAAGGGAAAGAACTCCATTTGCTTTGATTTTATTGCTGTATCCCCAGTGCC TAGAATAATGCTTAGCCTGCAATAAATATTTATTCATTGACT(SEQIDNO: 157) >NP031668.3T-cell-specificsurfaceglycoproteinCD28 precursor[Musmusculus] MTLRLLFLALNFFSVQVTENKILVKQSPLLVVDSNEVSLSCRYSYNLLAKEFRASLY KGVNSDVEVCVGNGNFTYQPQFRSNAEFNCDGDFDNETVTFRLWNLHVNHTDIYFCK IEFMYPPPYLDNERSNGTIIHIKEKHLCHTQSSPKLFWALVVVAGVLFCYGLLVTVA LCVIWTNSRRNRLLQSDYMNMTPRRPGLTRKPYQPYAPARDFAAYRP(SEQID NO:158) Human >NM_144615.2Homosapienstransmembraneand CD28H immunoglobulindomaincontaining2(TMIGD2),transcript variant1,mRNA GGAAGTCTGTCAACTGGGAGGGGGAGAGGGGGGTGATGGGCCAGGAATGGGGTCCCC GGGCATGGTGCTGGGCCTCCTGGTGCAGATCTGGGCCCTGCAAGAAGCCTCAAGCCT GAGCGTGCAGCAGGGGCCCAACTTGCTGCAGGTGAGGCAGGGCAGTCAGGCGACCCT GGTCTGCCAGGTGGACCAGGCCACAGCCTGGGAACGGCTCCGTGTTAAGTGGACAAA GGATGGGGCCATCCTGTGTCAACCGTACATCACCAACGGCAGCCTCAGCCTGGGGGT CTGCGGGCCCCAGGGACGGCTCTCCTGGCAGGCACCCAGCCATCTCACCCTGCAGCT GGACCCTGTGAGCCTCAACCACAGCGGGGCGTACGTGTGCTGGGCGGCCGTAGAGAT TCCTGAGTTGGAGGAGGCTGAGGGCAACATAACAAGGCTCTTTGTGGACCCAGATGA CCCCACACAGAACAGAAACCGGATCGCAAGCTTCCCAGGATTCCTCTTCGTGCTGCT GGGGGTGGGAAGCATGGGTGTGGCTGCGATCGTGTGGGGTGCCTGGTTCTGGGGCCG CCGCAGCTGCCAGCAAAGGGACTCAGGTAACAGCCCAGGAAATGCATTCTACAGCAA CGTCCTATACCGGCCCCGGGGGGCCCCAAAGAAGAGTGAGGACTGCTCTGGAGAGGG GAAGGACCAGAGGGGCCAGAGCATTTATTCAACCTCCTTCCCGCAACCGGCCCCCCG CCAGCCGCACCTGGCGTCAAGACCCTGCCCCAGCCCGAGACCCTGCCCCAGCCCCAG GCCCGGCCACCCCGTCTCTATGGTCAGGGTCTCTCCTAGACCAAGCCCCACCCAGCA GCCGAGGCCAAAAGGGTTCCCCAAAGTGGGAGAGGAGTGAGAGATCCCAGGAGACCT CAACAGGACCCCACCCATAGGTACACACAAAAAAGGGGGGATCGAGGCCAGACACGG TGGCTCACGCCTGTAATCCCAGCAGTTTGGGAAGCCGAGGCGGGTGGAACACTTGAG GTCAGGGGTTTGAGACCAGCCTGGCTTGAACCTGGGAGGCGGAGGTTGCAGTGAGCC GAGATTGCGCCACTGCACTCCAGCCTGGGCGACAGAGTGAGACTCCGTCTCAAAAAA AACAAAAAGCAGGAGGATTGGGAGCCTGTCAGCCCCATCCTGAGACCCCGTCCTCAT TTCTGTAATGATGGATCTCGCTCCCACTTTCCCCCAAGAACCTAATAAAGGCTTGTG AAGAAAAAGCAAAAAAAAAAAAAAAAAA(SEQIDNO:159) >NP_653216.2transmembraneandimmunoglobulindomain- containingprotein2isoform1precursor[Homosapiens] MGSPGMVLGLLVQIWALQEASSLSVQQGPNLLQVRQGSQATLVCQVDQATAWERLRV KWTKDGAILCQPYITNGSLSLGVCGPQGRLSWQAPSHLTLQLDPVSLNHSGAYVCWA AVEIPELEEAEGNITRLFVDPDDPTQNRNRIASFPGFLFVLLGVGSMGVAAIVWGAW FWGRRSCQQRDSGNSPGNAFYSNVLYRPRGAPKKSEDCSGEGKDQRGQSIYSTSFPQ PAPRQPHLASRPCPSPRPCPSPRPGHPVSMVRVSPRPSPTQQPRPKGFPKVGEE (SEQIDNO:160) HumanCD2 >NM_001328609.2HomosapiensCD2molecule(CD2), transcriptvariant1,mRNA AGTCTCACTTCAGTTCCTTTTGCATGAAGAGCTCAGAATCAAAAGAGGAAACCAACC CCTAAGATGAGCTTTCCATGTAAATTTGTAGCCAGCTTCCTTCTGATTTTCAATGTT TCTTCCAAAGGTGCAGTCTCCAAAGAGATTACGAATGCCTTGGAAACCTGGGGTGCC TTGGGTCAGGACATCAACTTGGACATTCCTAGTTTTCAAATGAGTGATGATATTGAC GATATAAAATGGGAAAAAACTTCAGACAAGAAAAAGATTGCACAATTCAGAAAAGAG AAAGAGACTTTCAAGGAAAAAGATACATATAAGCTATTTAAAAATGGAACTCTGAAA ATTAAGCATCTGAAGACCGATGATCAGGATATCTACAAGGTATCAATATATGATACA AAAGGAAAAAATGTGTTGGAAAAAATATTTGATTTGAAGATTCAAGAGAGGGTCTCA AAACCAAAGATCTCCTGGACTTGTATCAACACAACCCTGACCTGTGAGGTAATGAAT GGAACTGACCCCGAATTAAACCTGTATCAAGATGGGAAACATCTAAAACTTTCTCAG AGGGTCATCACACACAAGTGGACCACCAGCCTGAGTGCAAAATTCAAGTGCACAGCA GGGAACAAAGTCAGCAAGGAATCCAGTGTCGAGCCTGTCAGCTGTCCAGGAGGCAGC ATCCTTGGCCAGAGTAATGGGCTCTCTGCCTGGACCCCTCCCAGCCATCCCACTTCT CTTCCTTTTGCAGAGAAAGGTCTGGACATCTATCTCATCATTGGCATATGTGGAGGA GGCAGCCTCTTGATGGTCTTTGTGGCACTGCTCGTTTTCTATATCACCAAAAGGAAA AAACAGAGGAGTCGGAGAAATGATGAGGAGCTGGAGACAAGAGCCCACAGAGTAGCT ACTGAAGAAAGGGGCCGGAAGCCCCACCAAATTCCAGCTTCAACCCCTCAGAATCCA GCAACTTCCCAACATCCTCCTCCACCACCTGGTCATCGTTCCCAGGCACCTAGTCAT CGTCCCCCGCCTCCTGGACACCGTGTTCAGCACCAGCCTCAGAAGAGGCCTCCTGCT CCGTCGGGCACACAAGTTCACCAGCAGAAAGGCCCGCCCCTCCCCAGACCTCGAGTT CAGCCAAAACCTCCCCATGGGGCAGCAGAAAACTCATTGTCCCCTTCCTCTAATTAA AAAAGATAGAAACTGTCTTTTTCAATAAAAAGCACTGTGGATTTCTGCCCTCCTGAT GTGCATATCCGTACTTCCATGAGGTGTTTTCTGTGTGCAGAACATTGTCACCTCCTG AGGCTGTGGGCCACAGCCACCTCTGCATCTTCGAACTCAGCCATGTGGTCAACATCT GGAGTTTTTGGTCTCCTCAGAGAGCTCCATCACACCAGTAAGGAGAAGCAATATAAG TGTGATTGCAAGAATGGTAGAGGACCGAGCACAGAAATCTTAGAGATTTCTTGTCCC CTCTCAGGTCATGTGTAGATGCGATAAATCAAGTGATTGGTGTGCCTGGGTCTCACT ACAAGCAGCCTATCTGCTTAAGAGACTCTGGAGTTTCTTATGTGCCCTGGTGGACAC TTGCCCACCATCCTGTGAGTAAAAGTGAAATAAAAGCTTTGACTAGA(SEQID NO:161) >NP_001315538.1T-cellsurfaceantigenCD2isoform1 precursor[Homosapiens] MSFPCKFVASFLLIFNVSSKGAVSKEITNALETWGALGQDINLDIPSFQMSDDIDDI KWEKTSDKKKIAQFRKEKETFKEKDTYKLFKNGTLKIKHLKTDDQDIYKVSIYDTKG KNVLEKIFDLKIQERVSKPKISWTCINTTLTCEVMNGTDPELNLYQDGKHLKLSQRV ITHKWTTSLSAKFKCTAGNKVSKESSVEPVSCPGGSILGQSNGLSAWTPPSHPTSLP FAEKGLDIYLIIGICGGGSLLMVFVALLVFYITKRKKQRSRRNDEELETRAHRVATE ERGRKPHQIPASTPQNPATSQHPPPPPGHRSQAPSHRPPPPGHRVQHQPQKRPPAPS GTQVHQQKGPPLPRPRVQPKPPHGAAENSLSPSSN(SEQIDNO:162) MouseCD2 >NM_013486.2MusmusculusCD2antigen(Cd2),mRNA GCCTCACCACAGTCCTGACAGAAAGAACTCAGAGTCACCCCTGGGAAAAGAACTCTA AAGATGAAATGTAAATTCCTGGGTAGCTTCTTTCTGCTCTTCAGCCTTTCCGGCAAA GGGGCGGACTGCAGAGACAATGAGACCATCTGGGGTGTCTTGGGTCATGGCATCACC CTGAACATCCCCAACTTTCAAATGACTGATGATATTGATGAGGTGCGATGGGTAAGG AGGGGCACCCTGGTCGCAGAGTTTAAAAGGAAGAAGCCACCTTTTTTGATATCAGAA ACGTATGAGGTCTTAGCAAACGGATCCCTGAAGATAAAGAAGCCGATGATGAGAAAC GACAGTGGCACCTATAATGTAATGGTGTATGGCACAAATGGGATGACTAGGCTGGAG AAGGACCTGGACGTGAGGATTCTGGAGAGGGTCTCAAAGCCCATGATCCACTGGGAA TGCCCCAACACAACCCTGACCTGTGCGGTCTTGCAAGGGACAGATTTTGAACTGAAG CTGTATCAAGGGGAAACACTACTCAATAGTCTCCCCCAGAAGAACATGAGTTACCAG TGGACCAACCTGAACGCACCATTCAAGTGTGAGGCGATAAACCCGGTCAGCAAGGAG TCTAAGATGGAAGTTGTTAACTGTCCAGAGAAAGGTCTGTCCTTCTATGTCACAGTG GGGGTCGGTGCAGGAGGACTCCTCTTGGTGCTCTTGGTGGCGCTTTTTATTTTCTGT ATCTGCAAGAGGAGAAAACGGAACAGGAGGAGAAAAGATGAAGAGCTGGAAATAAAA GCTTCCAGAACAAGCACTGTGGAAAGGGGCCCCAAGCCGCACTCAACCCCAGCCGCA GCAGCGCAGAATTCAGTGGCGCTCCAAGCTCCTCCTCCACCTGGCCATCACCTCCAG ACACCTGGCCATCGTCCCTTGCCTCCAGGCCACCGTACCCGTGAGCACCAGCAGAAG AAGAGACCTCCTCCATCAGGCACACAGATTCACCAGCAGAAAGGCCCTCCTTTACCC AGACCCCGAGTTCAGCCAAAACCTCCCTGTGGGAGTGGAGATGGTGTTTCACTGCCG CCCCCTAATTAAGAAGGCAGAGTTCGTCATTTCCAATAAAAAGCTGTGTGGATTTAT CTTC(SEQIDNO:163) >NP_038514.1T-cellsurfaceantigenCD2precursor[Mus musculus] MKCKFLGSFFLLFSLSGKGADCRDNETIWGVLGHGITLNIPNFQMTDDIDEVRWVRR GTLVAEFKRKKPPFLISETYEVLANGSLKIKKPMMRNDSGTYNVMVYGTNGMTRLEK DLDVRILERVSKPMIHWECPNTTLTCAVLQGTDFELKLYQGETLLNSLPQKNMSYQW TNLNAPFKCEAINPVSKESKMEVVNCPEKGLSFYVTVGVGAGGLLLVLLVALFIFCI CKRRKRNRRRKDEELEIKASRTSTVERGPKPHSTPAAAAQNSVALQAPPPPGHHLQT PGHRPLPPGHRTREHQQKKRPPPSGTQIHQQKGPPLPRPRVQPKPPCGSGDGVSLPP PN(SEQIDNO:164) HumanLFA-3 >NM_001779.3HomosapiensCD58molecule(CD58), (CD58) transcriptvariant1,mRNA GAACTTAGGGCTGCTTGTGGCTGGGCACTCGCGCAGAGGCCGGCCCGACGAGCCATG GTTGCTGGGAGCGACGCGGGGCGGGCCCTGGGGGTCCTCAGCGTGGTCTGCCTGCTG CACTGCTTTGGTTTCATCAGCTGTTTTTCCCAACAAATATATGGTGTTGTGTATGGG AATGTAACTTTCCATGTACCAAGCAATGTGCCTTTAAAAGAGGTCCTATGGAAAAAA CAAAAGGATAAAGTTGCAGAACTGGAAAATTCTGAATTCAGAGCTTTCTCATCTTTT AAAAATAGGGTTTATTTAGACACTGTGTCAGGTAGCCTCACTATCTACAACTTAACA TCATCAGATGAAGATGAGTATGAAATGGAATCGCCAAATATTACTGATACCATGAAG TTCTTTCTTTATGTGCTTGAGTCTCTTCCATCTCCCACACTAACTTGTGCATTGACT AATGGAAGCATTGAAGTCCAATGCATGATACCAGAGCATTACAACAGCCATCGAGGA CTTATAATGTACTCATGGGATTGTCCTATGGAGCAATGTAAACGTAACTCAACCAGT ATATATTTTAAGATGGAAAATGATCTTCCACAAAAAATACAGTGTACTCTTAGCAAT CCATTATTTAATACAACATCATCAATCATTTTGACAACCTGTATCCCAAGCAGCGGT CATTCAAGACACAGATATGCACTTATACCCATACCATTAGCAGTAATTACAACATGT ATTGTGCTGTATATGAATGGTATTCTGAAATGTGACAGAAAACCAGACAGAACCAAC TCCAATTGATTGGTAACAGAAGATGAAGACAACAGCATAACTAAATTATTTTAAAAA CTAAAAAGCCATCTGATTTCTCATTTGAGTATTACAATTTTTGAACAACTGTTGGAA ATGTAACTTGAAGCAGCTGCTTTAAGAAGAAATACCCACTAACAAAGAACAAGCATT AGTTTTGGCTGTCATCAACTTATTATATGACTAGGTGCTTGCTTTTTTTGTCAGTAA ATTGTTTTTACTGATGATGTAGATACTTTTGTAAATAAATGTAAATATGTACACAAG TGA(SEQIDNO:165) >NP_001770.1lymphocytefunction-associatedantigen3 isoform1[Homosapiens] MVAGSDAGRALGVLSVVCLLHCFGFISCFSQQIYGVVYGNVTFHVPSNVPLKEVLWK KQKDKVAELENSEFRAFSSFKNRVYLDTVSGSLTIYNLTSSDEDEYEMESPNITDTM KFFLYVLESLPSPTLTCALINGSIEVQCMIPEHYNSHRGLIMYSWDCPMEQCKRNST SIYFKMENDLPQKIQCTLSNPLFNTTSSIILTTCIPSSGHSRHRYALIPIPLAVITT CIVLYMNGILKCDRKPDRINSN(SEQIDNO:166) HumanCD48 >NM_001778.4HomosapiensCD48molecule(CD48), transcriptvariant1,mRNA CTTTTTCTAGCCAGGCTCTCAACTGTCTCCTGCGTTGCTGGGAAGTTCTGGAAGGAA GCATGTGCTCCAGAGGTTGGGATTCGTGTCTGGCTCTGGAATTGCTACTGCTGCCTC TGTCACTCCTGGTGACCAGCATTCAAGGTCACTTGGTACATATGACCGTGGTCTCCG GCAGCAACGTGACTCTGAACATCTCTGAGAGCCTGCCTGAGAACTACAAACAACTAA CCTGGTTTTATACTTTCGACCAGAAGATTGTAGAATGGGATTCCAGAAAATCTAAGT ACTTTGAATCCAAATTTAAAGGCAGGGTCAGACTTGATCCTCAGAGTGGCGCACTGT ACATCTCTAAGGTCCAGAAAGAGGACAACAGCACCTACATCATGAGGGTGTTGAAAA AGACTGGGAATGAGCAAGAATGGAAGATCAAGCTGCAAGTGCTTGACCCTGTACCCA AGCCTGTCATCAAAATTGAGAAGATAGAAGACATGGATGACAACTGTTATCTGAAAC TGTCATGTGTGATACCTGGCGAGTCTGTAAACTACACCTGGTATGGGGACAAAAGGC CCTTCCCAAAGGAGCTCCAGAACAGTGTGCTTGAAACCACCCTTATGCCACATAATT ACTCCAGGTGTTATACTTGCCAAGTCAGCAATTCTGTGAGCAGCAAGAATGGCACGG TCTGCCTCAGTCCACCCTGTACCCTGGCCCGGTCCTTTGGAGTAGAATGGATTGCAA GTTGGCTAGTGGTCACGGTGCCCACCATTCTTGGCCTGTTACTTACCTGAGATGAGC TCTTTTAACTCAAGCGAAACTTCAAGGCCAGAAGATCTTGCCTGTTGGTGATCATGC TCCTCACCAGGACAGAGACTGTATAGGCTGACCAGAAGCATGCTGCTGAATTATCAA CGAGGATTTTCAAGTTAACTTTTAAATACTGGTTATTATTTAATTTTATATCCCTTT GTTGTTTTCTAGTACACAGAGATATAGAGATACACATGCTTTTTTCCCACCCAAAAT TGTGACAACATTATGTGAATGTTTTATTATTTTTTAAAATAAACATTTGATATAATT GTCAATTAACTGAA(SEQIDNO:167) >NP_001769.2CD48antigenisoform1precursor[Homo sapiens] MCSRGWDSCLALELLLLPLSLLVTSIQGHLVHMTVVSGSNVTLNISESLPENYKQLT WFYTFDQKIVEWDSRKSKYFESKFKGRVRLDPQSGALYISKVQKEDNSTYIMRVLKK TGNEQEWKIKLQVLDPVPKPVIKIEKIEDMDDNCYLKLSCVIPGESVNYTWYGDKRP FPKELQNSVLETTLMPHNYSRCYTCQVSNSVSSKNGTVCLSPPCTLARSEGVEWIAS WLVVTVPTILGLLLT(SEQIDNO:168) MouseCD48 >NM_007649.5MusmusculusCD48antigen(Cd48),transcript variant1,mRNA ATACGACTTCCGGTTTTGGGTTTTGCTTCCTGATTGAAGGGCAGGCGCCCTGACTTC TCTTACAGTTGTCTCCAGTGTTCTGGGGAAGCTTCTCTAAGTATTATGTGCTTCATA AAACAGGGATGGTGTCTGGTCCTGGAACTGCTACTGCTGCCCTTGGGAACTGGATTT CAAGGTCATTCAATACCAGATATAAATGCCACCACCGGCAGCAATGTAACCCTGAAA ATCCATAAGGACCCACTTGGACCATATAAACGTATCACCTGGCTTCATACTAAAAAT CAGAAGATTTTAGAGTACAACTATAATAGTACAAAGACAATCTTCGAGTCTGAATTT AAAGGCAGGGTTTATCTTGAAGAAAACAATGGTGCACTTCATATCTCTAATGTCCGG AAAGAGGACAAAGGTACCTACTACATGAGAGTGCTGCGTGAAACTGAGAACGAGTTG AAGATAACCCTGGAAGTATTTGATCCTGTGCCCAAGCCTTCCATAGAAATCAATAAG ACTGAAGCGTCGACTGATTCCTGTCACCTGAGGCTATCGTGTGAGGTAAAGGACCAG CATGTTGACTATACTTGGTATGAGAGCTCGGGACCTTTCCCCAAAAAGAGTCCAGGA TATGTGCTCGATCTCATCGTCACACCACAGAACAAGTCTACATTTTACACCTGCCAA GTCAGCAATCCTGTAAGCAGCAAGAACGACACAGTGTACTTCACTCTACCTTGTGAT CTAGCCAGATCTTCTGGAGTATGTTGGACTGCAACTTGGCTAGTGGTCACAACACTC ATCATTCACAGGATCCTGTTAACCTGACAAGAACTCTTCTCACCCAAGAAGGCAACT TGGAAGCACAGAGTCTTGCCTTCATCCCTAGCAGTGTTCCTAGCCAGCGAAGCAACT CTGGCTCTATTGGACAAAGGAAAATGTGTTACTGAACGTCTGCGAGAGTTTGCATGC ATGCTCTATGAAACAAGCACAGGACCTTGTACAGTGCTCCACCACTGACCTGTGTGC CCAGTCCTTTACAAAGATTTCAAATCAACCTTTTAAAAACTGTGCATAATATCTAAT TTTATATACCCTAGTTGTTTCCCAACATATATTAAAGATAAATGCATTCTTTTTACC AAAATGTGACTATATTATTTTCATGTTTTCATATCTCTTTTTAAAATAAATTCTTTT AAAAAACT(SEQIDNO:169) >NP_031675.1CD48antigenisoform1precursor[Mus musculus] MCFIKQGWCLVLELLLLPLGTGFQGHSIPDINATTGSNVTLKIHKDPLGPYKRITWL HTKNQKILEYNYNSTKTIFESEFKGRVYLEENNGALHISNVRKEDKGTYYMRVLRET ENELKITLEVEDPVPKPSIEINKTEASTDSCHLRLSCEVKDQHVDYTWYESSGPFPK KSPGYVLDLIVTPQNKSTFYTCQVSNPVSSKNDTVYFTLPCDLARSSGVCWTATWLV VTTLIIHRILLT(SEQIDNO:170) HumanCD226 >NM_006566.4HomosapiensCD226molecule(CD226), transcriptvariant1,mRNA GCAGATGGGAAGAAGCGTTAGAGCGAGCAGCACTCACATCTCAAGAACCAGCCTTTC AAACAGTTTCCAGAGATGGATTATCCTACTTTACTTTTGGCTCTTCTTCATGTATAC AGAGCTCTATGTGAAGAGGTGCTTTGGCATACATCAGTTCCCTTTGCCGAGAACATG TCTCTAGAATGTGTGTATCCATCAATGGGCATCTTAACACAGGTGGAGTGGTTCAAG ATCGGGACCCAGCAGGATTCCATAGCCATTTTCAGCCCTACTCATGGCATGGTCATA AGGAAGCCCTATGCTGAGAGGGTTTACTTTTTGAATTCAACGATGGCTTCCAATAAC ATGACTCTTTTCTTTCGGAATGCCTCTGAAGATGATGTTGGCTACTATTCCTGCTCT CTTTACACTTACCCACAGGGAACTTGGCAGAAGGTGATACAGGTGGTTCAGTCAGAT AGTTTTGAGGCAGCTGTGCCATCAAATAGCCACATTGTTTCGGAACCTGGAAAGAAT GTCACACTCACTTGTCAGCCTCAGATGACGTGGCCTGTGCAGGCAGTGAGGTGGGAA AAGATCCAGCCCCGTCAGATCGACCTCTTAACTTACTGCAACTTGGTCCATGGCAGA AATTTCACCTCCAAGTTCCCAAGACAAATAGTGAGCAACTGCAGCCACGGAAGGTGG AGCGTCATCGTCATCCCCGATGTCACAGTCTCAGACTCGGGGCTTTACCGCTGCTAC TTGCAGGCCAGCGCAGGAGAAAACGAAACCTTCGTGATGAGATTGACTGTAGCCGAG GGTAAAACCGATAACCAATATACCCTCTTTGTGGCTGGAGGGACAGTTTTATTGTTG TTGTTTGTTATCTCAATTACCACCATCATTGTCATTTTCCTTAACAGAAGGAGAAGG AGAGAGAGAAGAGATCTATTTACAGAGTCCTGGGATACACAGAAGGCACCCAATAAC TATAGAAGTCCCATCTCTACCAGTCAACCTACCAATCAATCCATGGATGATACAAGA GAGGATATTTATGTCAACTATCCAACCTTCTCTCGCAGACCAAAGACTAGAGTTTAA GCTTATTCTTGACATGAGTGCATTAGTAATGACTCTTATGTACTCATGCATGGATCT TTATGCAATTTTTTTCCACTACCCAAGGTCTACCTTAGATACTAGTTGTCTGAATTG AGTTACTTTGATAGGAAAAATACTTCATTACCTAAAATCATTTTTCATAGAACTGTT TCAGAAAACCTGACTCTAACTGGTTTATATACAAAAGAAAACTTACTGTATCATATA ACAGAATGATCCAGGGGAGATTAAGCTTTGGGCAAGGGCTATTTACCAGGGCTTAAA TGTTGTGTCTAGAATTAAGTATGGGCATAAACTGGCTTCTGAATCCCTTTCCAGAGT GTTGGATCCATTTCCCTGGTCTTGGCCTCACTCTCATGCAGGCTTTCCTCTTGTGTT GGCAAGATGGCTGCCAACTCTTGGCAATTCATACATCCTTGTTTCTGTCTGGTAGAG AGTTTGCTTCTCAAATGGAGCAAACAAATTTGATTATTTTTTCATTGTTAAATAGGC AACATGACCAGAAAGGATGGAATGGCTTAAGTAAACTAAGGGTTCACTTCTAGAGCT GAGAAGCAGGGTCAAAGCACAATACTGGGCAATTCAGAGCATGGTTAGAAGAGGAAA GGGGAGTCTCAAAGCTGGAGAGTTTACCAACAAATATTGACTGCAGTGATTAACCAA GACATTTTTGTTAACTAAAAAGTGAAATATGGGATGGATTCTAGAAATGGGGTATCT CTGTCCATACTTCTAGAATCCACTCTATCAGCATAGTCCAGAAGAATACCTGGCAGT AGAAGAAATGAATATTCAAGAGGAAGATAAATGCGAGAGGGCAATCCTTTACTATTC TCATATTTATTTATCTCTCATTCTGTATAGAATTCTTGCCGCCATCCCAGGTCTAGC CTTAGGAGCAAATGTAGTAGATAGTCGAATAATAAATAACTTAATGTTTTGGACATA TTTTGTCTACTTTTGAGAATTATTTTTAATATGTAAATTCTCTCAAAAGGGTCAGGC ACCTAGTTATTATTTTTTAATGATTATGTGAAAGTTGAATATAATATACCACTAAAA GTGACAGTTGAAAGTGGTGGCATAGGACGGTAGGGTAGAAATTTGGGAGGGAAAAAA GAAATTGGGAGGGTACAGGCAACAGGAGAAAGGAATCAAACCACAGAAAAATACAAA GGGAAACTTCTGCTTCACTATTCAGACAAAGACAGCCCTAATGACATCACCAACAGT CAAAGCAATTAGAGACCATACCTAATATTGTTTAAATTCTAGATGTAGGCTAACAAT GAAAAGTATTTGCCAAACTGAATAAAACTGTCATGGTTACCTTGAAAGGACAATGGT TATTGTTAAATATAGTGATCATTCATGTCTAAAAGATTCATTATTTATCTCTAAAGA TTTCTAAAGACCACCATCTAGAAAAGATTCATTATGAAGGCTGTATTTAAATATCAA AGTTGTGGACTTCATGATAATCTTAAATAAAGCAAATCCAAATTCTCCTGTTGCCTA GACAGATTCTAAGATGTAATTTACACTTTTAAGCTAATTAGTGAGTATTTTATGATT TTAGCCTTAAACACCATGTATGCCAAATAATGCACTTGTTTTGTGAATTACAGAAAT GGTAAGTGCCCACATTTCTGTGAATTATAAAATTTGTGAGTTTCTTTTAACCCTTTT CAGGAGTGAAAAAATAAAAACGACCATTTCCTGGTTGTGCTTAAGTATATGCAAGAA GGGTAAACTCTCATTTTTATTATGTTTGCTTAAAGATCTTTTTATACCTGGATTCAT GAAATGTTTCCACAAATATATTAGTGTAACAAACTTGAAAGGCAGTTTACAAGAAAG CACTCTACTATCAGATCAATCAAAGATTCTGTGAGTGAATTTATTGGTTTGCATGGT GAAGCAAGCTTAGCATCAATTAAAAGGTAAATAATTTCTTTTCTGAATGGTAAAGAC AATCAAAATATTACTTTCTGGAAAACTCCAATAACCAAATTCTCAATGATTAGTGTA TGTGAGCAGGAAAACATTTTTACAGTTGTAGTATGGGGAAATATAAATCCAATTTTA AGAGAGAAAATTATGACTGGGTGTGGAAGGGACAGTATAGTCAGATACCATTGTCAT GGTGGTTTTTACTGGGAACTTCATGAAAGACTTTTGTAGCAAACCACTGCAGTATTG CAAAGCCTCCAGAACATTTGGAACTTGTCTCTTTTTCCTTGTGTGTGTTTGTGTTTT TGGTCTCTCATTCAAAATATTGATGAGAACTATTTACTCTGTCCTTTCTTCTCTATA TATTCTTCCTCTACAGAGTGTAGGGTTTTTTCAGGAATTTGGAGCCATCTGAAGTCC TCCCAAAAATTCTCTGACGTCTTCTGATGCTCCTGTTATACCCTCAGGGGTAATGCT TGTGAAATTCCATTCATTCATTTTCTTTCTCTGGACATCTTTACTTACCAAAGCACT TTCATTGTCATCTTTTTAACATCATTCTTAATTCGTGATAGTTTTGGGACTCTCCCT AGTGTATGTTTCTCCCCCTCTACTCTTTTGCACCTATGATTCTGATTGTTACTAAGA AAGCAGATGAAAAACAGATCCACAGAATAAACGATCAGAATTCCAGTAAATTCTATT TTAAATACAGATACTTTTTACAAGTTGCTGCTTTGGAAGCAAAATGCTTCTTAAGTT TTACATATATATATATATATATACATATATATATACACATATAATTTATATCGATGG ATAATACATTAAGAATCTATGCTTCCTTTGAATGCCATTAATATTTATGTTAAAGTA ACCAATGAAAGGAAATTACTTTGTTATAATAAGATAGGAAGACTTGTTAATGGAGTA CACAGTTTTGTCAGGGAAAGAACACATCTTATTGAACTATGATGACTATGCATTGAC TATATTATTATAAGAGATACCTTCAAACTTTATTTAAAGAACTTTAGGTATAATATG TTGAGAAAATAAAATAGAAATTTCATTTACTTGTAATCATGCTTAAAATGGGAGGCA GGTAGGTGAAGATATAATTTTTAGTAAAAACTCCAATTTATGTTTTAAGTAATTCAG TGTATTACTAAAATACTATATATATAAACTTAAAATACATGGGTTATCAATTTAAAA GACAAAGTAAGTAAAAATACTTTTAGTAGGCATTCGTGGATTGTGAACATCCAAGTT ATATTGGTTTGTATAGAATGGCATTAAGTAAAAATTACAGCTGTATAACAGTAGTTT TCTAAATTGAGAGAGTCCACATTGTAATTAGAGATCACTGTGACCAAAATGCTTCTC CTTGATTTATAATGATGTACTGTATTTTGTACTGCTTATATGAAATTTCAGCAAGAT TGACGATATTATAAAGATGCTTATAAAGTGTAAGTGGAGACGCTAAATTGTGAGTAC AAAGTTTCTTTTTCACAACAGTGATAAGAAAATATCTTTAAAAAATATAAGACAATA TAAACATGTCATCATTAGTTTAGCTACTATTAAAATGTAACATCTAGAAAGTACTGA TCTCCACCTTCAGACTTCTGTATAAGTATATTTTTTCACTGATCTGTTCATTAGAGT TCTTCCAGCCAAGACTCTGGGCTCTTAAAACATGTATCTGAAAACTAAAAACAAGTT AATTTTTTTAAAAGCTTCTCTATTTCTAGTGATTCAATAGGTAGAAAAATAGCTTCT AGAATTAACTGCAATGCTTTCTAAGGAAATTTTATAAATCCTCAAGGTCGGTTTACA CATATTTTTCCAGATTCAGAGCACTAACTATCTTGTAAGATGTAAGAAAAGGTCCAT TTGGAAGTATGAGTAATAAATGTCTGGGATAATTCTGGTTTATTTCGTATTATCCTT GTTAGAATAAGTTATATGGTCAACCTGTTCAGAACACTTTTTCTAGTGTTAGTGTGT ACTTTTGGATTTTTGGTTCTTGTAGGGTATAGAAATATTTTCCTTTGTCTTGTATTC TGTTGTTTTGAATGAATAAAACACAATGTTTCACGATCACTACTTTCATTTGCCATG GAGAAATAGCAGGGAAAAATTTCTACAGAATAAAATTAACTGATGAATTACATGCAG AAAAAATTCAAATCAATGATACATTGTAATTTTTATCTCAATGCAATGTTCTTTGTA TTTTATTTTATTATTATTTTTTTGAGACGGAGTTTCACTTTTGTTGCCCGGGCTGGA GTGCAATGGCACAATCTCGGCTCACCACAACCTCTGCCTCCCGGATTCAAGTGATTC TCCTGCCTCAGCCTCCTGAATAGCTGGGATTACAGGCATATGCCAACATGCCTGGCT AATTTTGTATTTTTAGTGGAGACGGGGTTTCTCCACGTTGGTCAGACTTGTCTTGAA CTCTGGACCTCAGGTGATCCACCTGCCTCAGCCTCCTAAATTGCTGGGATTACAGGC ATGAGCGACCACTCCTGGCCTTGTTCTTTGTATTTTATAAGTGCATGTAGTGCAAAG GGTCAAAGGGCTTTACAGGTTTTTTGTTTGTTTGTTTTTGTTTTTCCCGAAACATAG TAGTCCCTTGCCCTTCCTCATTTTTGTTACCTTGAGACAACAAATTTTACTACTTCT AACTCATTATTTTATTTATGTTCACTTTTCTGAATAGCATGCTTATGACACTAATAC TTTTTTTTTCAATTTTAGACATTCATTATTCATTTAGATGTCTTTCTCTCCCCAAAC TCACCACATAAAATACTCTTCTCATGTCTCTTTCAGAAATATTTGTATTAAAATATG ATTATATCAATATTTGGCATTTATTTCTTATGACCTTGCCAGTACTCTTAGTTAAAC TACATGGTAAAAATGATTTTGCTTTCCCTCCTACATAACTTTTTTTCCACCTAGAGC TAATAATTGTCATTCTGGGGACTGACTTTTTCTGTATTTACCATAAATTGACCTGAA ACTCCCCTGTGATGCAGCAGGAATTCTACCAACGTCAACTTCCTTAGAAAGACTCCA TTAGAAGCTTGACTTGGGGCTAGAAGGAGAGGCACACAACTGCCATCCTGGTGTCTC CCTTCATCCAGAAAAAGGGGGAGGAATACATGAAACCTAGAATCCACTCTAAAACAT TTTCCAGAACAAAAGGACATGTGTTTCCGTGTTGTAAATGTTTAACGAGTGCCCATA ACAAGGAATAATAAGTCTATTATGTTTGCTTTTGTGTCTGTAAAAGTTGGGGGTATT GGTTGTAAGCACGAAAACAGATACTGACTGTTGAAGAAAAAAAAAAATACGAGGTCA GGAGTTTGAGACCAACTTGGCCAATATGGTGAAACCCTGTCTTAGTAAAAATAGAAA AATTAGCCAGGCCTGGTGGCACGCACCTGTAGTCCCAGCTACTTGGGAGGCTGAGGC AGAAGAATCGCTTGAACCCGGGAGGCAGAGGTTGCAGTGAGCCAAGATCGCACCACT GCACTCCACCCTGGGCAACAGAGCGAGACTCCGTCTCAAAAAAAAAAAAAAAAAAAA AAAAAAAAAGTTAAGTATTTGAACATAGGGGTGGCTCATAGAATTCCCAGGACACCC GATGGAGTAGGCTTGCAAAACACAACATGTGGCAACTCCAGTGGGAAACGAGGCAGG AAACACTCGTTTCCTGCAGAAAGCAACAATTTGGGCTTCGATACCCTCCCTAGAACA CAGGGCAGTGAATCTGAGCAGCATCAGTACCCCACGTTCGGATGAGTCCTGAGCCCC TATTTTTATTCACTGACTTATTCCAAAATCAGTGTCTCTTAAATATATCTGGAAGGC AGCAGCTTGTATCTCCCCCTTCAGCTTCCATAGTGGCAGTCAGGGTACAACTTACTT TCCAAACAGAACACACTGCGACATTCCCTCCAGGCTCGTTGAAGAACTTCAACTGAC AAATGTCCCTCCTCGACCAGATGATAGTTTTCTTAAAGGCAGGGTTTAATATACCCT TTTATAAATGTTTCAAGGCCCTGTGTAATACCTGAGTTTATTCCAGATGTAACTAAA TATATCCAAGATTGTTTTAAAATAAATTGCTGAAAAAACAAATAAATACAGTTAGTA TCTATATCAATATTCTCAGTTGGCAGTTTTGCAATAATGGCCGATAGTTCATTTTTA GTAACACTATTGACATTGCATTTGGATATTAGGGTTTACTAATCATCCGCATGTATA CATTGCATATTTTTCTAGACTTTAACTTTATTCAAATCTATTGATTTTTAAACCTGC AACTTATGTCTAGACACAGGTATACCTTTACAAGAACTACCATTTTTTTTGGTAACA TACTACCTCCAAAATTTCAAGTAAGAAGTTGATTTTTGTCCATTTTTAAATGGAAAA CTTGTAATCAAAATGCCACAAAATTATACTGTGTATCATTTGACCTATAGAAACCAA TATTATTACAGGAAGAAAGCAGAGCCAATCTTCTACCTGTGGTCAAATAAGTGGAGG CCCTTTCTAGACTAAGTTCTCATGAGTTTAAAATACCAAGCATAAGTTCTCCAAATT CCTGAAAAGGAAGCCTTGTGTTGTATTGCCCAGCCATATTTGTAAGACATAAAAATA AAACTTGAGAAGAAGCTATGATAACTTACTTTCTTCATTCTTCAAAATTTACATAAT CTCAACTGATTTTATGTTTTTATGAAAATGCATTCTTAAGATATATCCTTATTCAAT CATGTATTCATTACATCCTTTATGCCAGGTATCCAAAAGTACTTACAGTGACTAAGA CCATTATTCTTTGATCAGCTGCCTGAGTAAGACTTTGAGCTCTCCAATATACTCTCA GTGATACTAAGTTTTCTGAGTAACAGCTTTGGATGTGGCTTCAGTTGAGCTGATTTA TCCCACACTTTATTTTTATCGTATAATGGTCCTCAGAAGCAAATTTTGATTTTAGCT CACATAAAAAATGTACAAAGAAATGTAATGGCTCAGTAGCTTCTAGAGATAGAGATT ACTCTTCTAACCTTTCTGTAATTTTGTATGTCTATTTTATAATTCTTTCAATGTCTA ATGAATAGCTATCTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCAGGCTGGAGTGC AGTGGTGCGACCTCGGCTCACCGCAAGCTGCGTCTTCCAGGTTCACGCCATTCTCCT GCCTCAGCCTCCCGAGTAGCTGGGACTTCAGGCGCCCACCACCATGCCCAGCTAATT TTTTTGTATTTTTAGTAGAGACGGGGTTTCACCGTGTTAGCCAGGGTGGTCTCGATC TCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAACGTGCTGGGATTACAGGAGTG AGCCACCGCGCCCGGCCTCCTTAGTTTCTTAAGGTGGAAGCCTAGATTATTGATTTT ATATGTTGTTTTCTTTTCCAATAGTGGCACTTAATGCTATAAATTTCACTTTGTTCC ACAAGTTTTGGTAAGCTCTATTTTTATTTTCATTTAGTCCAAAATATTTTAAAATTT CTTTTGATATTTCTTCTTTGAGCCATGAATTATTTACAATGTGTTGTTTAATCTCTA TATATTTTGGGATTTTTCTACTTTATATCTCTTACAGATTTCTAACTTAATTTCATC ATGTTTTAAAAACATTCTTTGTATAATTTCTATTCTTTTAAATTTTTCAGGTGTATT TTATGGCCCAGAATATGGTCTATCTTGTAGAATGTTTCATGTGATCTTAAGAAGAAT GTTCATTCTGCTGTTGAGTGTAATATTCTACAAATGTCCATTAGATTAAACTGATTG ATACCACCGTTCAGATTATCTATATCCTTTCTGATTTTCCCTCTTCTTGATCTATCA CATACTGACAGATCAAGTGATCAAGTCTCGTTAAAGACTGCAAGTAAAATAGTGGAT TTTTCTATTTCTCCTTGCAGTTTTGTTAGTTTTTGTCTCATGTATCTTGATACTCTT GTTAGTACATATACTTTCAGAATCGTTAGGTTTTCTTGGAGAATTGACCCCTTTACC ACATGTAATGTCCCTTTTATTCTTGATAATCTTTCTTGTTCTGTCTGCTTTTTCTGA TATTAACATAACTTTCAGTTTTTTAAAAAATTAACATTAGCATCTCACATCTTTATC CTTTTAATTTTAAATTATCTAAATATTTATATTTAATGTGCCTTTCTTATAGACAAT GTATAGTTGCGTCTATTTGTAATTTCCCCACTTTTCTTACTTAAAAATGTTGTAGAT ATATAGGAGTTGTATATATTTGGGGGGTACATGTGATGTTTTGATACCTGTATACAA TATGTAATGATCATATTGGGTAATCGTGATATCTGTCACCTCTAACATTCATCTTTT TTGTGTGTTTAAACCCACCACTTCTAATTGGTACATTTAGATTATTCAAATTTAAGT GATTATTGATATAGTTGGATTAATATCTACTATGTTTGTAACTTTTCTATCCTTGCA CTCGTTCTTTCTTTTTTATCCTCCTTTTTCTGTGTTCTCTGATTTTAACTGGGGTTT TTACATGATTTAATTTTCTCTCGTGGCATATCTTTCATTGATCAACCTAGGTTTTTC TCCTTTTCCCCTCTTTTTTTTGGTATTTATTCTATTTAGTGTTATCTGAGCTACCTG AGTTGGTGTCTATCACTAATTTTGGCAAGTTCCCAGACGTTATTACTTCTAACATTC TTTTGCTCCATTCTTTCTTCTTCTTCAATTATTCCATAGTCTTGAATATTCTGGGTT TTTCCCACTCTTTGAATTTTAGTTTGAAAAGTTTCTATTGGCCTAGCTTCAAAGTCA TTCATTCTTCCTTCGGGGTTCCAAGTCAACTGATAATTGCATCAAAGATATCCTTCC TTTCTATTACTATGTTTTTTATTGCTACCATTTCTTTTTTATTCCTTCTTAGTGTTT CCATCTTTCTTCTTACATTATCCATCTGTTGTCTATTTTTTTCATGAGAGCTCTTAA CATATTAATGATAAGTTCCATGTCTGATAATTCTGACACGTGTCATGTCTCTATCTG GTTCCAATGATTGCTTTATCTCTTCAGACCATGACTTTTCTTGCCTTTTGACGTTCT TTGACATTTTTTTTGAATTTTTTGTTGCAAGCCAGATCTGGTGTGTTATGTAATAGG AACAGGTAAATAAGTCTTTAGCTTGCAGACTTATCTTAATCTGACTAACTATTAGAC TGTGTTTAAAGTCTGTTATAACCATAGGTGCTAAATTTCTTCAAATTCCTCTAGTGT CTTTGTTTTGTTTGTTCATGTGTTTTTCCCCTTCTTGAGTTCAGGCTTCCCTAAGTG CTCCTCTTCAGAGAGACTTTCTGTCTTTCAGCTCTTTCCTCTGCAATTCACTGTTAC TATACTGGAGCCCTGTTGGTGTAGTACTAAGCTGTGGGAAAGGAGAGTGCTCTGTAA TCTTACAGTGAAATCTCAGTCTTTTAGTGGGTCTGTGTCTGGGACATTCACAGAGCT TCTCCAGTGGTATTGCTTCCTCATCCTCAACTCTCTTTCCTGGCTGCAGCATTCCCA ATGTATTTCTTTGAAGGCCTGCCCCCTGTTGACTGTTATTTTCCCTCTTTCCTTAAG TGGGACAGGGAGACTTCAGGGGCTGGGATGAGGTTTGGGAATTGTGCTTGGCAGAGT CCTTTCCATCTTTGTTACCAAGAAGGTTCATGGCTTATTTCTCAATGGATGTCCCTC TCTATCTGTTGCCAGAGCCACGAGGAAATTTTTCTTGGATCCTCATAATGAGAACCT TGGAGTTTCCTACTGGAAAAGCCCTTGAATGTGTGGAGTGCCTCAAGAGCACAGCCC CCATGGGTTTCTTGCTCACACCAGTCCACAAACAGATGCCAGCAATTCACCCAACTT ACCATATAAAGGCTCATACTAGTTTATGGCTCCAGTGCTTTGACTCCAGATAAATGG CTATTGGTTGCGTATCTCTCTGGATGTATCTGTATCTCCAGATTTTGGGGTGGCAGT TTGCTCAGGACCTTGGTTCTCTAATAGGTCTAATAAGAAAAGTCATTGATTTTCAGC TTTCCAACTTTCCAGCTTTGTCTTGTTATAAGCATGGCAGCAACATCTTCCATGCCT TAACATGATGACACTAAAGGCAGAAGTCGATCTCCATGTATAAACATTTTAACACAT ATGTTTTTTGTTATCGTGGTTTCTGACCTGTCTCTTTGCCCTGACTTTCTGATACTG CACTAGGGTTCCTGTTGCTGGACTCCATTCCATATGACTTGCTCTCGTCTAGGCTGC TCTTTGGCTCATCTTTATAAATCATGATCCAAAATGAAGCACATATTTATTTTTTAA ATAAATATGAAATGAAGTATAGACATCAAACTGAAGATGAGTAGATCATACTGAGTT TCACTGTCTGTGCTTGGATCAACATCAGGCCTTATACAAATATTCAAGTCCAGAGGC AAAAGGTAATAAGGAAAATTTGTAGCACAAGCCACAAGGAGATAACATGTCAAGTCT ATGCGATTGGAAATAAACTAAAGATGAACTGCTGGGGATGCTCACTCATCACAGAGC TCAGTCTAAAGCACCAGATTTCACAAGCATTTTTTGGGGGAAATTCTGTTAAAATGA AATATGAGTCACATGGTGGTGTTTCACTCATCATATGTGTTCAATATTAATTCATTT TAAGGTTTAGTTGCACAAAAGGTAAATGAGAATTAGAAGACTCCATGGGTAAGAGGA GCCACAGAAGTAAAGCATTGTCAAGGGTTCTATGTCTATATATTTAGATATTAGGCT TCTGAGAAAAAAACACAATAGGAAGGAAGATGAACACAACAGAGGGCAGAAGGTCTA TACGTCCTGAGGCCTTTTATGCAACGTTTGTTTGTGGAATGTTTTTTAAGAATGTGT GAGAGTCATTTTAATGTGAAATAAAGACCTACGTCTACA(SEQIDNO:171) >NP_006557.2CD226antigenisoformaprecursor[Homo sapiens] MDYPTLLLALLHVYRALCEEVLWHTSVPFAENMSLECVYPSMGILTQVEWFKIGTQQ DSIAIFSPTHGMVIRKPYAERVYFLNSTMASNNMTLFFRNASEDDVGYYSCSLYTYP QGTWQKVIQVVQSDSFEAAVPSNSHIVSEPGKNVTLTCQPQMTWPVQAVRWEKIQPR QIDLLTYCNLVHGRNFTSKFPRQIVSNCSHGRWSVIVIPDVTVSDSGLYRCYLQASA GENETFVMRLTVAEGKTDNQYTLFVAGGTVLLLLFVISITTIIVIFLNRRRRRERRD LFTESWDTQKAPNNYRSPISTSQPTNQSMDDTREDIYVNYPTESRRPKTRV(SEQ IDNO:172) MouseCD226 >NM_178687.2MusmusculusCD226antigen(Cd226), transcriptvariant1,mRNA ACACAGAAGACTTCTTGACTTCAGGAGACACTGCTGTATGAAACAGTGCTTGCTATC AGTGGCTGCTGGAAGAGGCTGTGGTGGAAAGAAAACCTCAACTGCAGGCCAGAGTTG GTTCCCCAAAAGAGGCAAACTCCCAGTGCTAGCCAGAGGCTAGGAAGCTCTAAGCAA CCCACTTATCTGCAAGGAGAGTTACGCCCAAAGAGCATCAAGTCCAACCTCCTGAAC TGTTTCCAGAGATGGCTTATGTTACTTGGCTTTTGGCTATTCTTCATGTGCACAAAG CACTGTGTGAAGAGACATTGTGGGACACAACAGTTCGGCTTTCTGAGACTATGACTC TGGAATGTGTATATCCATTGACGCATAACTTAACCCAGGTGGAGTGGACCAAGAACA CTGGCACAAAGACAGTGAGCATAGCAGTTTACAACCCTAACCATAATATGCATATAG AATCTAACTACCTCCATAGAGTACACTTCCTAAACTCAACAGTGGGGTTCCGCAACA TGAGCCTTTCCTTTTACAATGCCTCAGAAGCAGACATTGGCATCTACTCCTGCTTGT TTCATGCTTTCCCAAATGGACCTTGGGAAAAGAAGATAAAAGTAGTCTGGTCAGATA GTTTTGAGATAGCAGCACCCTCGGATAGCTACCTGTCTGCAGAACCTGGACAAGATG TCACACTCACTTGCCAGCTTCCAAGGACTTGGCCAGTGCAACAAGTCATATGGGAAA AAGTCCAGCCCCATCAGGTAGACATCTTAGCTTCCTGTAACCTATCTCAAGAGACAA GATACACTTCAAAGTACCTAAGACAAACAAGGAGCAACTGTAGCCAGGGGAGCATGA AGAGCATCCTCATCATTCCAAATGCCATGGCCGCTGACTCAGGACTTTACAGATGTC GCTCAGAGGCCATTACAGGAAAAAACAAGTCCTTTGTCATAAGGCTGATCATAACTG ATGGTGGAACCAATAAACATTTTATCCTTCCCATCGTTGGAGGGTTAGTTTCACTGT TACTTGTCATCCTAATTATCATCATTTTCATTTTATATAACAGGAAGAGACGGAGAC AGGTGAGAATTCCACTTAAAGAGCCCAGGGATAAACAGAGTAAGGTAGCCACCAACT GCAGAAGTCCTACTTCTCCCATCCAGTCTACAGATGATGAAAAAGAGGACATTTATG TAAACTATCCAACTTTCTCTCGAAGACCAAAACCAAGACTCTAAGCTGCTCTTTTGG CCTGAACACATTAGTGATGACTTCTATGGCATGGAATTTTACCCATGATTTCCTTAC CACTAGGATCTACATTGATAAAAAAAATTGATTAAATTTATTTCATCTCATATATAG AAGTACTTTATTACCTGGAAACATTCTTAATAGAGATTCATTAGAAAACCCAAATCT AATGTTCATGTGTTCAAGGAACCTTCTTCCATTATGTAACAGAACAGTCTAGAGAAG ATTAAGGACCACATGGCTTTCTTGCTCTACTTGAAATTAATTGTGAGCATAAGCTTG TTTCTGGAGTCTTCTTACATTGTTGGTTCTACTTACATACTACTGGTCCAACTCTCA TGCTGTTTCTCTCAGATGTTCCCATGATGGTTGCCAAGGACACTTGATAGAAAGACT ACTGGTTAAACACAATAAACAAAGTTCATTATTCACTTATTAGCAAGAAGGTAGCAT TATCATAAAGGATTAGATGACTTAAGTTAGCTATAGGTTCAAGACCTGGACTAAAGT ATTACTTGGAAATTCTGAGTATTGCTAAAAAGGAGGATGAAAGGGACCTAGAAGTTG AGTTATTACTAAAAACTTTGAGTGCGAAGATATTACTCATTAACCAGATAACAAGTG AATATGCTGTAGCATCAACATAATTCAAAAGAGTAAAGAAATGGCTAGGAATGAGGT AGTTGTGTAATTATTTCTTCTCTTACTAGTTTCAAATAAATTCATCTCTAATTCTAT AGAGAATTCTTGCCTCCCATTCAGGACTGGCCTTCTATACAGTGAGATGGTCCAGTA AGAAATAATTTTTATTAGTGTTTTTTCTATTTTGAGAATTATTTTAATATATATTTT AATATATAAACTTGTGAGTTAAATTTTTTTTTTGCAAAATTAGCACATGAAAAGAGA TTGATGGTTTTAAGTAGTAGAACACAGTAGTGTAGGAATCTGAGAGCAGAGAGTTTG GGAGGGGGTGAAGAGAAAACAACATCACCAAATAGTGATATATAAGAGAAAATCTGT GCTTCAGAGTTTGATCAGGGCCATCTCTCCCAACTCTGCTGGAACTGAGAGAATGCA CCTGATGTTGTCTCCATTTTAGATAGAGAAAAAAAAAACCCGAATATTTATAAAACT AAATAAAACTATAGTTACCTCAAAACTATGGGGATCACTATAACATAGAATAGAATA GAATAGAATAGAATAGAATAGAATAGAATAGAATAG(SEQIDNO:173) >NP_848802.2CD226antigenisoformaprecursor[Mus musculus] MAYVTWLLAILHVHKALCEETLWDTTVRLSETMTLECVYPLTHNLTQVEWTKNTGTK TVSIAVYNPNHNMHIESNYLHRVHFLNSTVGFRNMSLSFYNASEADIGIYSCLFHAF PNGPWEKKIKVVWSDSFEIAAPSDSYLSAEPGQDVTLTCQLPRTWPVQQVIWEKVQP HQVDILASCNLSQETRYTSKYLRQTRSNCSQGSMKSILIIPNAMAADSGLYRCRSEA ITGKNKSFVIRLIITDGGTNKHFILPIVGGLVSLLLVILIIIIFILYNRKRRRQVRI PLKEPRDKQSKVATNCRSPTSPIQSTDDEKEDIYVNYPTFSRRPKPRL(SEQID NO:174) HumanDR3 >NM_003790.3HomosapiensTNFreceptorsuperfamilymember 25(TNFRSF25),transcriptvariant2,mRNA GAAGGCGGAACCACGACGGGCAGAGAGCACGGAGCCGGGAAGCCCCTGGGCGCCCGT CGGAGGGCTATGGAGCAGCGGCCGCGGGGCTGCGCGGCGGTGGCGGCGGCGCTCCTC CTGGTGCTGCTGGGGGCCCGGGCCCAGGGCGGCACTCGTAGCCCCAGGTGTGACTGT GCCGGTGACTTCCACAAGAAGATTGGTCTGTTTTGTTGCAGAGGCTGCCCAGCGGGG CACTACCTGAAGGCCCCTTGCACGGAGCCCTGCGGCAACTCCACCTGCCTTGTGTGT CCCCAAGACACCTTCTTGGCCTGGGAGAACCACCATAATTCTGAATGTGCCCGCTGC CAGGCCTGTGATGAGCAGGCCTCCCAGGTGGCGCTGGAGAACTGTTCAGCAGTGGCC GACACCCGCTGTGGCTGTAAGCCAGGCTGGTTTGTGGAGTGCCAGGTCAGCCAATGT GTCAGCAGTTCACCCTTCTACTGCCAACCATGCCTAGACTGCGGGGCCCTGCACCGC CACACACGGCTACTCTGTTCCCGCAGAGATACTGACTGTGGGACCTGCCTGCCTGGC TTCTATGAACATGGCGATGGCTGCGTGTCCTGCCCCACGAGCACCCTGGGGAGCTGT CCAGAGCGCTGTGCCGCTGTCTGTGGCTGGAGGCAGATGTTCTGGGTCCAGGTGCTC CTGGCTGGCCTTGTGGTCCCCCTCCTGCTTGGGGCCACCCTGACCTACACATACCGC CACTGCTGGCCTCACAAGCCCCTGGTTACTGCAGATGAAGCTGGGATGGAGGCTCTG ACCCCACCACCGGCCACCCATCTGTCACCCTTGGACAGCGCCCACACCCTTCTAGCA CCTCCTGACAGCAGTGAGAAGATCTGCACCGTCCAGTTGGTGGGTAACAGCTGGACC CCTGGCTACCCCGAGACCCAGGAGGCGCTCTGCCCGCAGGTGACATGGTCCTGGGAC CAGTTGCCCAGCAGAGCTCTTGGCCCCGCTGCTGCGCCCACACTCTCGCCAGAGTCC CCAGCCGGCTCGCCAGCCATGATGCTGCAGCCGGGCCCGCAGCTCTACGACGTGATG GACGCGGTCCCAGCGCGGCGCTGGAAGGAGTTCGTGCGCACGCTGGGGCTGCGCGAG GCAGAGATCGAAGCCGTGGAGGTGGAGATCGGCCGCTTCCGAGACCAGCAGTACGAG ATGCTCAAGCGCTGGCGCCAGCAGCAGCCCGCGGGCCTCGGAGCCGTTTACGCGGCC CTGGAGCGCATGGGGCTGGACGGCTGCGTGGAAGACTTGCGCAGCCGCCTGCAGCGC GGCCCGTGACACGGCGCCCACTTGCCACCTAGGCGCTCTGGTGGCCCTTGCAGAAGC CCTAAGTACGGTTACTTATGCGTGTAGACATTTTATGTCACTTATTAAGCCGCTGGC ACGGCCCTGCGTAGCAGCACCAGCCGGCCCCACCCCTGCTCGCCCCTATCGCTCCAG CCAAGGCGAAGAAGCACGAACGAATGTCGAGAGGGGGTGAAGACATTTCTCAACTTC TCGGCCGGAGTTTGGCTGAGATCGCGGTATTAAATCTGTGAAAGAAAACAAAACAAA ACAAAAACGGCTTCTTGGCGTTTCTGCGGGGCTGGGGTGTTAAGTGGACTGGACTTT TCTCGAGGGATTCGAAGGGGACGGGAATCTTGTCACCCCGGGATCTGGCACCCATGG TGGAGTCCAGTGTGGCCTTAGCTCCCAAGCCTGCCCCTCCCGAGTCCACTCTGGCTC AATTACCCCGAGAAGGAGAGAGCAAGTCGCGGCCACAGCGAGTGAGTGAACCGGAGC CCAGATGAGAGCGCTTTAATGGGGCTGCGAGGTGGCGGAGACAGGGTCGGGATGGGG TGCAGCAGTTGGAGACACAGGGTCAGGGCCCCTCATCCTCTATTCACTCCACCGGGG CAGTGAAAGGGTCCCGGCAGCGAGTGGGTC(SEQIDNO:175) >NP_003781.1tumornecrosisfactorreceptorsuperfamily member25isoform2precursor[Homosapiens] MEQRPRGCAAVAAALLLVLLGARAQGGTRSPRCDCAGDFHKKIGLFCCRGCPAGHYL KAPCTEPCGNSTCLVCPQDTFLAWENHHNSECARCQACDEQASQVALENCSAVADTR CGCKPGWFVECQVSQCVSSSPFYCQPCLDCGALHRHTRLLCSRRDTDCGTCLPGFYE HGDGCVSCPTSTLGSCPERCAAVCGWRQMFWVQVLLAGLVVPLLLGATLTYTYRHCW PHKPLVTADEAGMEALTPPPATHLSPLDSAHTLLAPPDSSEKICTVQLVGNSWTPGY PETQEALCPQVTWSWDQLPSRALGPAAAPTLSPESPAGSPAMMLQPGPQLYDVMDAV PARRWKEFVRTLGLREAEIEAVEVEIGRFRDQQYEMLKRWRQQQPAGLGAVYAALER MGLDGCVEDLRSRLQRGP(SEQIDNO:176) MouseDR3 >NM_033042.4Musmusculustumornecrosisfactorreceptor superfamily,member25(Tnfrsf25),transcriptvariant2, mRNA CTGCGTGGAGGGGAAATGGGCCAGAGGCTGCTGGCAGGGGGCCTCCTCTGCTGTACA CAAGCTGGTTTTGTAGACAGTGAGAGGGAAGCTGATCCCAGTCCCCTAACCCTGTTC TGCCCAGGAGCCTGAGAACTGAGCTTACTCGGGCAAATGCTAGGGCTTCAGAAATGG AGGAGCTGCCTAGGAGGGAGAGGTCACCTCCTGGGGCAGCCACACCAGGGTCAACTG CACGTGTTCTCCAGCCTCTGTTCCTACCACTGCTGCTGCTGCTGCTGCTGCTGCTTG GTGGCCAGGGCCAGGGCGGCATGTCTGGCAGGTGTGACTGTGCCAGTGAGTCCCAGA AGAGGTATGGCCCGTTTTGTTGCAGGGGCTGCCCAAAGGGACACTACATGAAGGCCC CCTGCGCAGAACCCTGTGGCAACTCCACCTGCCTTCCCTGTCCCTCGGACACCTTCT TGACCAGAGACAACCACTTTAAGACTGACTGTACCCGCTGCCAAGTCTGTGATGAAG AGGCCCTTCAAGTGACCCTTGAGAACTGCTCGGCAAAGTCGGACACCCACTGTGGCT GCCAGTCAGGCTGGTGTGTTGACTGCTCCACCGAGCCATGTGGGAAAAGCTCACCTT TCTCTTGTGTCCCATGCGGGGCTACAACACCAGTCCATGAGGCTCCAACCCCCCTGT TTTGGGTCCAGGTGCTTCTAGGAGTCGCGTTCCTTTTTGGGGCTATCCTGATCTGTG CATATTGTCGATGGCAGCCTTGTAAGGCCGTGGTCACTGCAGACACAGCTGGGACGG AGACCCTGGCCTCACCACAGACTGCCCATCTCTCAGCCTCAGACAGCGCCCACACCC TCCTGGCACCTCCAAGCAGTACTGGGAAAATCTGTACCACTGTCCAGTTGGTAGGCA ACAACTGGACCCCTGGCTTATCCCAGACTCAGGAGGTGGTCTGCGGACAGGCCTCAC AACCCTGGGATCAGCTGCCAAACAGAACTCTTGGAACTCCTCTGGCATCTCCGCTCT CGCCAGCGCCCCCTGCGGGCTCTCCGGCTGCTGTGCTCCAGCCTGGCCCGCAGCTCT ACGATGTGATGGATGCGGTCCCAGCACGAAGGTGGAAGGAGTTCGTGCGCACGCTGG GGCTGCGGGAAGCGGAAATTGAAGCCGTGGAGGTGGAAATCTGCCGCTTCCGAGACC AGCAGTATGAGATGCTCAAGCGCTGGCGTCAGCAGCAGCCTGCAGGCCTCGGTGCCA TCTATGCGGCTCTGGAGCGCATGGGTCTGGAAGGCTGTGCCGAGGACCTGCGCAGCC GCCTGCAGCGTGGCCCGTGATGGAAGGTCCATCAGCCACTTTGACACCCTAGTGACC CTTGAAGGAGCCTTAAGTATTGTTACTTATGCGTGTAGACATTTTATGTCAATTACT AACCCCCTGCCGTGGTCCTGCGTAGCAGGGCTGGCTGCCTCACTTTTGCTTATCTGC AGCACGGAGCTCCTGCTAAGGGAAGCGTCATGGAGAAATACCAGAAGGGGCCAAGTG ATTGGTTGCTCAGCTGTTAATTAGCCCGAGTTTGGACTTGGTATTAAATTTCGTAAG AAAAGCAGCTGCTTG(SEQIDNO:177) >NP_149031.2tumornecrosisfactorreceptorsuperfamily member25isoform2precursor[Musmusculus] MEELPRRERSPPGAATPGSTARVLQPLFLPLLLLLLLLLGGQGQGGMSGRCDCASES QKRYGPFCCRGCPKGHYMKAPCAEPCGNSTCLPCPSDTFLTRDNHFKTDCTRCQVCD EEALQVTLENCSAKSDTHCGCQSGWCVDCSTEPCGKSSPFSCVPCGATTPVHEAPTP LFWVQVLLGVAFLFGAILICAYCRWQPCKAVVTADTAGTETLASPQTAHLSASDSAH TLLAPPSSTGKICTTVQLVGNNWTPGLSQTQEVVCGQASQPWDQLPNRTLGTPLASP LSPAPPAGSPAAVLQPGPQLYDVMDAVPARRWKEFVRTLGLREAEIEAVEVEICRFR DQQYEMLKRWRQQQPAGLGAIYAALERMGLEGCAEDLRSRLQRGP(SEQIDNO: 178) HumanDcR3 >NM_003823.4HomosapiensTNFreceptorsuperfamilymember 6b(TNFRSF6B),mRNA GGACTTGGGCGGCCCCTCCGCAGGCGGACCGGGGGCAAAGGAGGTGGCATGTCGGTC AGGCACAGCAGGGTCCTGTGTCCGCGCTGAGCCGCGCTCTCCCTGCTCCAGCAAGGA CCATGAGGGCGCTGGAGGGGCCAGGCCTGTCGCTGCTGTGCCTGGTGTTGGCGCTGC CTGCCCTGCTGCCGGTGCCGGCTGTACGCGGAGTGGCAGAAACACCCACCTACCCCT GGCGGGACGCAGAGACAGGGGAGCGGCTGGTGTGCGCCCAGTGCCCCCCAGGCACCT TTGTGCAGCGGCCGTGCCGCCGAGACAGCCCCACGACGTGTGGCCCGTGTCCACCGC GCCACTACACGCAGTTCTGGAACTACCTAGAGCGCTGCCGCTACTGCAACGTCCTCT GCGGGGAGCGTGAGGAGGAGGCACGGGCTTGCCACGCCACCCACAACCGTGCCTGCC GCTGCCGCACCGGCTTCTTCGCGCACGCTGGTTTCTGCTTGGAGCACGCATCGTGTC CACCTGGTGCCGGCGTGATTGCCCCGGGCACCCCCAGCCAGAACACGCAGTGCCAGC CGTGCCCCCCAGGCACCTTCTCAGCCAGCAGCTCCAGCTCAGAGCAGTGCCAGCCCC ACCGCAACTGCACGGCCCTGGGCCTGGCCCTCAATGTGCCAGGCTCTTCCTCCCATG ACACCCTGTGCACCAGCTGCACTGGCTTCCCCCTCAGCACCAGGGTACCAGGAGCTG AGGAGTGTGAGCGTGCCGTCATCGACTTTGTGGCTTTCCAGGACATCTCCATCAAGA GGCTGCAGCGGCTGCTGCAGGCCCTCGAGGCCCCGGAGGGCTGGGGTCCGACACCAA GGGCGGGCCGCGCGGCCTTGCAGCTGAAGCTGCGTCGGCGGCTCACGGAGCTCCTGG GGGCGCAGGACGGGGCGCTGCTGGTGCGGCTGCTGCAGGCGCTGCGCGTGGCCAGGA TGCCCGGGCTGGAGCGGAGCGTCCGTGAGCGCTTCCTCCCTGTGCACTGATCCTGGC CCCCTCTTATTTATTCTACATCCTTGGCACCCCACTTGCACTGAAAGAGGCTTTTTT TTAAATAGAAGAAATGAGGTTTCTTAAAGCTTATTTTTATAAAGCTTTTTCATAAAA (SEQIDNO:179) >NP_003814.1tumornecrosisfactorreceptorsuperfamily member6Bprecursor[Homosapiens] MRALEGPGLSLLCLVLALPALLPVPAVRGVAETPTYPWRDAETGERLVCAQCPPGTF VQRPCRRDSPTTCGPCPPRHYTQFWNYLERCRYCNVLCGEREEEARACHATHNRACR CRTGFFAHAGFCLEHASCPPGAGVIAPGTPSQNTQCQPCPPGTFSASSSSSEQCQPH RNCTALGLALNVPGSSSHDTLCTSCTGFPLSTRVPGAEECERAVIDFVAFQDISIKR LQRLLQALEAPEGWGPTPRAGRAALQLKLRRRLTELLGAQDGALLVRLLQALRVARM PGLERSVRERFLPVH(SEQIDNO:180) HumanFasL >NM_000639.3HomosapiensFasligand(FASLG),transcript variant1,mRNA AGCAGTCAGCAACAGGGTCCCGTCCTTGACACCTCAGCCTCTACAGGACTGAGAAGA AGTAAAACCGTTTGCTGGGGCTGGCCTGACTCACCAGCTGCCATGCAGCAGCCCTTC AATTACCCATATCCCCAGATCTACTGGGTGGACAGCAGTGCCAGCTCTCCCTGGGCC CCTCCAGGCACAGTTCTTCCCTGTCCAACCTCTGTGCCCAGAAGGCCTGGTCAAAGG AGGCCACCACCACCACCGCCACCGCCACCACTACCACCTCCGCCGCCGCCGCCACCA CTGCCTCCACTACCGCTGCCACCCCTGAAGAAGAGAGGGAACCACAGCACAGGCCTG TGTCTCCTTGTGATGTTTTTCATGGTTCTGGTTGCCTTGGTAGGATTGGGCCTGGGG ATGTTTCAGCTCTTCCACCTACAGAAGGAGCTGGCAGAACTCCGAGAGTCTACCAGC CAGATGCACACAGCATCATCTTTGGAGAAGCAAATAGGCCACCCCAGTCCACCCCCT GAAAAAAAGGAGCTGAGGAAAGTGGCCCATTTAACAGGCAAGTCCAACTCAAGGTCC ATGCCTCTGGAATGGGAAGACACCTATGGAATTGTCCTGCTTTCTGGAGTGAAGTAT AAGAAGGGTGGCCTTGTGATCAATGAAACTGGGCTGTACTTTGTATATTCCAAAGTA TACTTCCGGGGTCAATCTTGCAACAACCTGCCCCTGAGCCACAAGGTCTACATGAGG AACTCTAAGTATCCCCAGGATCTGGTGATGATGGAGGGGAAGATGATGAGCTACTGC ACTACTGGGCAGATGTGGGCCCGCAGCAGCTACCTGGGGGCAGTGTTCAATCTTACC AGTGCTGATCATTTATATGTCAACGTATCTGAGCTCTCTCTGGTCAATTTTGAGGAA TCTCAGACGTTTTTCGGCTTATATAAGCTCTAAGAGAAGCACTTTGGGATTCTTTCC ATTATGATTCTTTGTTACAGGCACCGAGAATGTTGTATTCAGTGAGGGTCTTCTTAC ATGCATTTGAGGTCAAGTAAGAAGACATGAACCAAGTGGACCTTGAGACCACAGGGT TCAAAATGTCTGTAGCTCCTCAACTCACCTAATGTTTATGAGCCAGACAAATGGAGG AATATGACGGAAGAACATAGAACTCTGGGCTGCCATGTGAAGAGGGAGAAGCATGAA AAAGCAGCTACCAGGTGTTCTACACTCATCTTAGTGCCTGAGAGTATTTAGGCAGAT TGAAAAGGACACCTTTTAACTCACCTCTCAAGGTGGGCCTTGCTACCTCAAGGGGGA CTGTCTTTCAGATACATGGTTGTGACCTGAGGATTTAAGGGATGGAAAAGGAAGACT AGAGGCTTGCATAATAAGCTAAAGAGGCTGAAAGAGGCCAATGCCCCACTGGCAGCA TCTTCACTTCTAAATGCATATCCTGAGCCATCGGTGAAACTAACAGATAAGCAAGAG AGATGTTTTGGGGACTCATTTCATTCCTAACACAGCATGTGTATTTCCAGTGCAATT GTAGGGGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTATGACTAAAGAGAGAATGT AGATATTGTGAAGTACATATTAGGAAAATATGGGTTGCATTTGGTCAAGATTTTGAA TGCTTCCTGACAATCAACTCTAATAGTGCTTAAAAATCATTGATTGTCAGCTACTAA TGATGTTTTCCTATAATATAATAAATATTTATGTAGATGTGCATTTTTGTGAAATGA AAACATGTAATAAAAAGTATATGTTAGGATACAAATAA(SEQIDNO:181) >NP_000630.1tumornecrosisfactorligandsuperfamily member6isoform1[Homosapiens] MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPPPLPPP PPPPPLPPLPLPPLKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAEL RESTSQMHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLL SGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGK MMSYCTTGQMWARSSYLGAVENLTSADHLYVNVSELSLVNFEESQTFFGLYKL (SEQIDNO:182) MouseFasL >NM_010177.4MusmusculusFasligand(TNFsuperfamily, member6)(Fasl),transcriptvariant1,mRNA TGAGGCTTCTCAGCTTCAGATGCAAGTGAGTGGGTGTCTCACAGAGAAGCAAAGAGA AGAGAACAGGAGAAAGGTGTTTCCCTTGACTGCGGAAACTTTATAAAGAAAACTTAG CTTCTCTGGAGCAGTCAGCGTCAGAGTTCTGTCCTTGACACCTGAGTCTCCTCCACA AGGCTGTGAGAAGGAAACCCTTTCCTGGGGCTGGGTGCCATGCAGCAGCCCATGAAT TACCCATGTCCCCAGATCTTCTGGGTAGACAGCAGTGCCACTTCATCTTGGGCTCCT CCAGGGTCAGTTTTTCCCTGTCCATCTTGTGGGCCTAGAGGGCCGGACCAAAGGAGA CCGCCACCTCCACCACCACCTGTGTCACCACTACCACCGCCATCACAACCACTCCCA CTGCCGCCACTGACCCCTCTAAAGAAGAAGGACCACAACACAAATCTGTGGCTACCG GTGGTATTTTTCATGGTTCTGGTGGCTCTGGTTGGAATGGGATTAGGAATGTATCAG CTCTTCCACCTGCAGAAGGAACTGGCAGAACTCCGTGAGTTCACCAACCAAAGCCTT AAAGTATCATCTTTTGAAAAGCAAATAGCCAACCCCAGTACACCCTCTGAAAAAAAA GAGCCGAGGAGTGTGGCCCATTTAACAGGGAACCCCCACTCAAGGTCCATCCCTCTG GAATGGGAAGACACATATGGAACCGCTCTGATCTCTGGAGTGAAGTATAAGAAAGGT GGCCTTGTGATCAACGAAACTGGGTTGTACTTCGTGTATTCCAAAGTATACTTCCGG GGTCAGTCTTGCAACAACCAGCCCCTAAACCACAAGGTCTATATGAGGAACTCTAAG TATCCTGAGGATCTGGTGCTAATGGAGGAGAAGAGGTTGAACTACTGCACTACTGGA CAGATATGGGCCCACAGCAGCTACCTGGGGGCAGTATTCAATCTTACCAGTGCTGAC CATTTATATGTCAACATATCTCAACTCTCTCTGATCAATTTTGAGGAATCTAAGACC TTTTTCGGCTTGTATAAGCTTTAAAAGAAAAAGCATTTTAAAATGATCTACTATTCT TTATCATGGGCACCAGGAATATTGTCTTGAATGAGAGTCTTCTTAAGACCTATTGAG ATTAATTAAGACTACATGAGCCACAAAGACCTCATGACCGCAAGGTCCAACAGGTCA GCTATCCTTCATTTTCTCGAGGTCCATGGAGTGGTCCTTAATGCCTGCATCATGAGC CAGATGGAAGGAGGTCTGTGACTGAGGGACATAAAGCTTTGGGCTGCTGTGTGACAA TGCAGAGGCACAGAGAAAGAACTGTCTGATGTTAAATGGCCAAGAGAATTTTAACCA TTGAAGAAGACACCTTTACACTCACTTCCAGGGTGGGTCTACTTACTACCTCACAGA GGCCGTTTTTGAGACATAGTTGTGGTATGAATATACAAGGGTGAGAAAGGAGGCTCA TTTGACTGATAAGCTAGAGACTGAAAAAAAGACAGTGTCTCATTGGCACCATCTTTA CTGTTACCTAATGTTTTCTGAGCCGACCTTTGATCCTAACGGAGAAGTAAGAGGGAT GTTTGAGGCACAAATCATTCTCTACATAGCATGCATACCTCCAGTGCAATGATGTCT GTGTGTTTGTATGTATGAGAGCAAACAGATTCTAAGGAGTCATATAAATAAAATATG TACATTATGGAGTACATATTAGAAACCTGTTACATTTGATGCTAGATATCTGAATGT TTCTTGGCAATAAACTCTAATAGTCTTCAAAATCTTTTATTATCAGCTACTGATGCT GTTTTTCTTTAATACAACTAGTATTTATGCTCTGAACATCCTAATGAGGAAAAGACA AATAAAATTATGTTATAGAATACAGAAATGCCTTAAGGACATAGACTTTGGAAA (SEQIDNO:183) >NP_034307.1tumornecrosisfactorligandsuperfamily member6isoform1[Musmusculus] MQQPMNYPCPQIFWVDSSATSSWAPPGSVFPCPSCGPRGPDQRRPPPPPPPVSPLPP PSQPLPLPPLTPLKKKDHNTNLWLPVVFFMVLVALVGMGLGMYQLFHLQKELAELRE FTNQSLKVSSFEKQIANPSTPSEKKEPRSVAHLTGNPHSRSIPLEWEDTYGTALISG VKYKKGGLVINETGLYFVYSKVYFRGQSCNNQPLNHKVYMRNSKYPEDLVLMEEKRL NYCTTGQIWAHSSYLGAVFNLTSADHLYVNISQLSLINFEESKTFFGLYKL(SEQ IDNO:184) HumanTIM-1 >NM_012206.3HomosapienshepatitisAviruscellular (CD365) receptor1(HAVCR1),transcriptvariant1,mRNA GACCAGGAGTCAGTTTGGCGGTTATGTGTGGGGAAGAAGCTGGGAAGTCAGGGGCTG TTTCTGTGGACAGCTTTCCCTGTCCTTTGGAAGGCACAGAGCTCTCAGCTGCAGGGA ACTAACAGAGCTCTGAAGCCGTTATATGTGGTCTTCTCTCATTTCCAGCAGAGCAGG CTCATATGAATCAACCAACTGGGTGAAAAGATAAGTTGCAATCTGAGATTTAAGACT TGATCAGATACCATCTGGTGGAGGGTACCAACCAGCCTGTCTGCTCATTTTCCTTCA GGCTGATCCCATAATGCATCCTCAAGTGGTCATCTTAAGCCTCATCCTACATCTGGC AGATTCTGTAGCTGGTTCTGTAAAGGTTGGTGGAGAGGCAGGTCCATCTGTCACACT ACCCTGCCACTACAGTGGAGCTGTCACATCCATGTGCTGGAATAGAGGCTCATGTTC TCTATTCACATGCCAAAATGGCATTGTCTGGACCAATGGAACCCACGTCACCTATCG GAAGGACACACGCTATAAGCTATTGGGGGACCTTTCAAGAAGGGATGTCTCTTTGAC CATAGAAAATACAGCTGTGTCTGACAGTGGCGTATATTGTTGCCGTGTTGAGCACCG TGGGTGGTTCAATGACATGAAAATCACCGTATCATTGGAGATTGTGCCACCCAAGGT CACGACTACTCCAATTGTCACAACTGTTCCAACCGTCACGACTGTTCGAACGAGCAC CACTGTTCCAACGACAACGACTGTTCCAATGACGACTGTTCCAACGACAACTGTTCC AACAACAATGAGCATTCCAACGACAACGACTGTTCTGACGACAATGACTGTTTCAAC GACAACGAGCGTTCCAACGACAACGAGCATTCCAACAACAACAAGTGTTCCAGTGAC AACAACTGTCTCTACCTTTGTTCCTCCAATGCCTTTGCCCAGGCAGAACCATGAACC AGTAGCCACTTCACCATCTTCACCTCAGCCAGCAGAAACCCACCCTACGACACTGCA GGGAGCAATAAGGAGAGAACCCACCAGCTCACCATTGTACTCTTACACAACAGATGG GAATGACACCGTGACAGAGTCTTCAGATGGCCTTTGGAATAACAATCAAACTCAACT GTTCCTAGAACATAGTCTACTGACGGCCAATACCACTAAAGGAATCTATGCTGGAGT CTGTATTTCTGTCTTGGTGCTTCTTGCTCTTTTGGGTGTCATCATTGCCAAAAAGTA TTTCTTCAAAAAGGAGGTTCAACAACTAAGTGTTTCATTTAGCAGCCTTCAAATTAA AGCTTTGCAAAATGCAGTTGAAAAGGAAGTCCAAGCAGAAGACAATATCTACATTGA GAATAGTCTTTATGCCACGGACTAAGACCCAGTGGTGCTCTTTGAGAGTTTACGCCC ATGAGTGCAGAAGACTGAACAGACATCAGCACATCAGACGTCTTTTAGACCCCAAGA CAATTTTTCTGTTTCAGTTTCATCTGGCATTCCAACATGTCAGTGATACTGGGTAGA GTAACTCTCTCACTCCAAACTGTGTATAGTCAACCTCATCATTAATGTAGTCCTAAT TTTTTATGCTAAAACTGGCTCAATCCTTCTGATCATTGCAGTTTTCTCTCAAATATG AACACTTTATAATTGTATGTTCTTTTTAGACCCCATAAATCCTGTATACATCAAAGA GAA(SEQIDNO:185) >NP_036338.2hepatitisAviruscellularreceptor1 isoformaprecursor[Homosapiens] MHPQVVILSLILHLADSVAGSVKVGGEAGPSVTLPCHYSGAVTSMCWNRGSCSLFTC QNGIVWTNGTHVTYRKDTRYKLLGDLSRRDVSLTIENTAVSDSGVYCCRVEHRGWFN DMKITVSLEIVPPKVTTTPIVTTVPTVTTVRTSTTVPTTTTVPMTTVPTTTVPTTMS IPTTTTVLTTMTVSTTTSVPTTTSIPTTTSVPVTTTVSTFVPPMPLPRQNHEPVATS PSSPQPAETHPTTLQGAIRREPTSSPLYSYTTDGNDTVTESSDGLWNNNQTQLFLEH SLLTANTTKGIYAGVCISVLVLLALLGVIIAKKYFFKKEVQQLSVSFSSLQIKALQN AVEKEVQAEDNIYIENSLYATD(SEQIDNO:186) MouseTIM-1 >NM_134248.2MusmusculushepatitisAviruscellular receptor1(Havcr1),transcriptvariant1,mRNA GTCAGTACCATGAATCAGATTCAAGTCTTCATTTCAGGCCTCATACTGCTTCTCCCA GGCGCTGTGGATTCTTATGTGGAAGTAAAGGGGGTGGTGGGTCACCCTGTCACACTT CCATGTACTTACTCAACATATCGTGGAATCACAACGACATGTTGGGGCCGAGGGCAA TGCCCATCTTCTGCTTGTCAAAATACACTTATTTGGACCAATGGACATCGTGTCACC TATCAGAAGAGCAGTCGGTACAACTTAAAGGGGCATATTTCAGAAGGAGATGTGTCC TTGACGATAGAGAACTCTGTTGAGAGTGACAGTGGTCTGTATTGTTGTCGAGTGGAG ATTCCTGGATGGTTTAATGATCAGAAAGTGACCTTTTCATTGCAAGTTAAACCAGAG ATTCCCACACGTCCTCCAAGAAGACCCACAACTACAAGGCCCACAGCTACAGGAAGA CCCACGACTATTTCAACAAGATCCACACATGTACCAACATCAACCAGAGTCTCTACC TCCACTCCTCCAACATCTACACACACATGGACTCACAAACCAGAACCCACTACATTT TGTCCCCATGAGACAACAGCTGAGGTGACAGGAATCCCATCCCATACTCCTACAGAC TGGAATGGCACTGTGACATCCTCAGGAGATACCTGGAGTAATCACACTGAAGCAATC CCTCCAGGGAAGCCGCAGAAAAACCCTACTAAGGGCTTCTATGTTGGCATCTGCATC GCAGCCCTGCTGCTACTGCTCCTTGTGAGCACCGTGGCTATCACCAGGTACATACTT ATGAAAAGGAAGTCAGCATCTCTAAGCGTGGTTGCCTTCCGTGTCTCTAAGATTGAA GCTTTGCAGAACGCAGCGGTTGTGCATTCCCGAGCTGAAGACAACATCTACATTGTT GAAGATAGACCTTGAGGGGCAGAATGAGTACCAGTGGCCCTCTGAGGGACCTTCTGC CTGAGATTTATAGAGACTGTCACTGATGTCATAGAGTCACACCCATTACAGCGCCAA GGCGATTTTCTGTGTTGGTTCTTCCAGCTGCAGCAGAGAGGGTAACCCTCTACTGTG TATACTCAAAACTCAGATTAACATCATCCTAATTTTGGTATCTGCACCACCTCCGTG TCTCTGCTCACTACAGAGATTCTCTCAAACATGAACGTTTTAGAAGTTTGTGTTTCC CTTAGTCAATGTAATCATTGGTAATACTATTCTATTCTTGGTTACTAAAACCATTAC TAAGAGAGGGATAGGAATTAAAAGTTGGTGTGAGGGGCCTCCTGAATTTAGAAGCAC TTGATTCTGTTTTATCTACTTTCTTGAAATGTTACTTCTACCCTTCCCAATGGGTAA AATCATGGGAGCATGGTGCCCTCATAGATAAATAGAAGAGAGTCTATTGCTGCCAAT ATAGATGGTTATGCTTTCTCATAGCTCTGAAAATATGACACATTTATTATGAGGTTG ATCTTAGGATAAGGATAGGTGTTTTATGTCAGGAGAGGTTATCATGGTGAATATGGA CCAGCAGACAGCAGTGGAGGAAAATAATGAACCAAGGGATTGAGTTCATTAGTGCTA ATTCTACTCCACTCCTGTCTTTATGCTCCTAAACTTACTGACTGAGCTCTGAATTAG GTGCTAGGAGGAGACAATGCAGACATGAAAGGGGAAGGAGCGCCTTCAGGACACAGG CTCTCTGCTGAGAGAAGTCCTATTTGCAGGTGTGATAGAGGTTGGGACAATCTCTGA GTTGTAAATTTCTAATTGTCTTCAGGCCATATTTATAGTTAAATTCATTTCCGAAAG ACATAGCATCTTCCCCAATGGGTCAGTTTGTCAAAATCAATAAAATATTTTGTTTTG CTAAGAATTAAAAAAAAAAAAAAAAAAA(SEQIDNO:187) >NP_599009.2hepatitisAviruscellularreceptor1 homologisoformaprecursor[Musmusculus] MNQIQVFISGLILLLPGAVDSYVEVKGVVGHPVTLPCTYSTYRGITTTCWGRGQCPS SACQNTLIWINGHRVTYQKSSRYNLKGHISEGDVSLTIENSVESDSGLYCCRVEIPG WFNDQKVTFSLQVKPEIPTRPPRRPTTTRPTATGRPTTISTRSTHVPTSTRVSTSTP PTSTHTWTHKPEPTTFCPHETTAEVTGIPSHTPTDWNGTVTSSGDTWSNHTEAIPPG KPQKNPTKGFYVGICIAALLLLLLVSTVAITRYILMKRKSASLSVVAFRVSKIEALQ NAAVVHSRAEDNIYIVEDRP(SEQIDNO:188) HumanPD-1 >NM_005018.3Homosapiensprogrammedcelldeath1 (PDCD1),mRNA GCTCACCTCCGCCTGAGCAGTGGAGAAGGCGGCACTCTGGTGGGGCTGCTCCAGGCA TGCAGATCCCACAGGCGCCCTGGCCAGTCGTCTGGGCGGTGCTACAACTGGGCTGGC GGCCAGGATGGTTCTTAGACTCCCCAGACAGGCCCTGGAACCCCCCCACCTTCTCCC CAGCCCTGCTCGTGGTGACCGAAGGGGACAACGCCACCTTCACCTGCAGCTTCTCCA ACACATCGGAGAGCTTCGTGCTAAACTGGTACCGCATGAGCCCCAGCAACCAGACGG ACAAGCTGGCCGCCTTCCCCGAGGACCGCAGCCAGCCCGGCCAGGACTGCCGCTTCC GTGTCACACAACTGCCCAACGGGCGTGACTTCCACATGAGCGTGGTCAGGGCCCGGC GCAATGACAGCGGCACCTACCTCTGTGGGGCCATCTCCCTGGCCCCCAAGGCGCAGA TCAAAGAGAGCCTGCGGGCAGAGCTCAGGGTGACAGAGAGAAGGGCAGAAGTGCCCA CAGCCCACCCCAGCCCCTCACCCAGGCCAGCCGGCCAGTTCCAAACCCTGGTGGTTG GTGTCGTGGGCGGCCTGCTGGGCAGCCTGGTGCTGCTAGTCTGGGTCCTGGCCGTCA TCTGCTCCCGGGCCGCACGAGGGACAATAGGAGCCAGGCGCACCGGCCAGCCCCTGA AGGAGGACCCCTCAGCCGTGCCTGTGTTCTCTGTGGACTATGGGGAGCTGGATTTCC AGTGGCGAGAGAAGACCCCGGAGCCCCCCGTGCCCTGTGTCCCTGAGCAGACGGAGT ATGCCACCATTGTCTTTCCTAGCGGAATGGGCACCTCATCCCCCGCCCGCAGGGGCT CAGCTGACGGCCCTCGGAGTGCCCAGCCACTGAGGCCTGAGGATGGACACTGCTCTT GGCCCCTCTGACCGGCTTCCTTGGCCACCAGTGTTCTGCAGACCCTCCACCATGAGC CCGGGTCAGCGCATTTCCTCAGGAGAAGCAGGCAGGGTGCAGGCCATTGCAGGCCGT CCAGGGGCTGAGCTGCCTGGGGGCGACCGGGGCTCCAGCCTGCACCTGCACCAGGCA CAGCCCCACCACAGGACTCATGTCTCAATGCCCACAGTGAGCCCAGGCAGCAGGTGT CACCGTCCCCTACAGGGAGGGCCAGATGCAGTCACTGCTTCAGGTCCTGCCAGCACA GAGCTGCCTGCGTCCAGCTCCCTGAATCTCTGCTGCTGCTGCTGCTGCTGCTGCTGC TGCCTGCGGCCCGGGGCTGAAGGCGCCGTGGCCCTGCCTGACGCCCCGGAGCCTCCT GCCTGAACTTGGGGGCTGGTTGGAGATGGCCTTGGAGCAGCCAAGGTGCCCCTGGCA GTGGCATCCCGAAACGCCCTGGACGCAGGGCCCAAGACTGGGCACAGGAGTGGGAGG TACATGGGGCTGGGGACTCCCCAGGAGTTATCTGCTCCCTGCAGGCCTAGAGAAGTT TCAGGGAAGGTCAGAAGAGCTCCTGGCTGTGGTGGGCAGGGCAGGAAACCCCTCCAC CTTTACACATGCCCAGGCAGCACCTCAGGCCCTTTGTGGGGCAGGGAAGCTGAGGCA GTAAGCGGGCAGGCAGAGCTGGAGGCCTTTCAGGCCCAGCCAGCACTCTGGCCTCCT GCCGCCGCATTCCACCCCAGCCCCTCACACCACTCGGGAGAGGGACATCCTACGGTC CCAAGGTCAGGAGGGCAGGGCTGGGGTTGACTCAGGCCCCTCCCAGCTGTGGCCACC TGGGTGTTGGGAGGGCAGAAGTGCAGGCACCTAGGGCCCCCCATGTGCCCACCCTGG GAGCTCTCCTTGGAACCCATTCCTGAAATTATTTAAAGGGGTTGGCCGGGCTCCCAC CAGGGCCTGGGTGGGAAGGTACAGGCGTTCCCCCGGGGCCTAGTACCCCCGCCGTGG CCTATCCACTCCTCACATCCACACACTGCACCCCCACTCCTGGGGCAGGGCCACCAG CATCCAGGCGGCCAGCAGGCACCTGAGTGGCTGGGACAAGGGATCCCCCTTCCCTGT GGTTCTATTATATTATAATTATAATTAAATATGAGAGCATGCTAA(SEQIDNO: 189) >NP_005009.2programmedcelldeathprotein1precursor [Homosapiens] MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFS NTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRAR RNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVV GVVGGLLGSLVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDF QWREKTPEPPVPCVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCS WPL(SEQIDNO:190) MousePD-1 >NM_008798.3Musmusculusprogrammedcelldeath1 (Pdcd1),mRNA TGAGCAGCGGGGAGGAGGAAGAGGAGACTGCTACTGAAGGCGACACTGCCAGGGGCT CTGGGCATGTGGGTCCGGCAGGTACCCTGGTCATTCACTTGGGCTGTGCTGCAGTTG AGCTGGCAATCAGGGTGGCTTCTAGAGGTCCCCAATGGGCCCTGGAGGTCCCTCACC TTCTACCCAGCCTGGCTCACAGTGTCAGAGGGAGCAAATGCCACCTTCACCTGCAGC TTGTCCAACTGGTCGGAGGATCTTATGCTGAACTGGAACCGCCTGAGTCCCAGCAAC CAGACTGAAAAACAGGCCGCCTTCTGTAATGGTTTGAGCCAACCCGTCCAGGATGCC CGCTTCCAGATCATACAGCTGCCCAACAGGCATGACTTCCACATGAACATCCTTGAC ACACGGCGCAATGACAGTGGCATCTACCTCTGTGGGGCCATCTCCCTGCACCCCAAG GCAAAAATCGAGGAGAGCCCTGGAGCAGAGCTCGTGGTAACAGAGAGAATCCTGGAG ACCTCAACAAGATATCCCAGCCCCTCGCCCAAACCAGAAGGCCGGTTTCAAGGCATG GTCATTGGTATCATGAGTGCCCTAGTGGGTATCCCTGTATTGCTGCTGCTGGCCTGG GCCCTAGCTGTCTTCTGCTCAACAAGTATGTCAGAGGCCAGAGGAGCTGGAAGCAAG GACGACACTCTGAAGGAGGAGCCTTCAGCAGCACCTGTCCCTAGTGTGGCCTATGAG GAGCTGGACTTCCAGGGACGAGAGAAGACACCAGAGCTCCCTACCGCCTGTGTGCAC ACAGAATATGCCACCATTGTCTTCACTGAAGGGCTGGGTGCCTCGGCCATGGGACGT AGGGGCTCAGCTGATGGCCTGCAGGGTCCTCGGCCTCCAAGACATGAGGATGGACAT TGTTCTTGGCCTCTTTGACCAGATTCTTCAGCCATTAGCATGCTGCAGACCCTCCAC AGAGAGCACCGGTCCGTCCCTCAGTCAAGAGGAGCATGCAGGCTACAGTTCAGCCAA GGCTCCCAGGGTCTGAGCTAGCTGGAGTGACAGCCCAGCGCCTGCACCAATTCCAGC ACATGCACTGTTGAGTGAGAGCTCACTTCAGGTTTACCACAAGCTGGGAGCAGCAGG CTTCCCGGTTTCCTATTGTCACAAGGTGCAGAGCTGGGGCCTAAGCCTATGTCTCCT GAATCCTACTGTTGGGCACTTCTAGGGACTTGAGACACTATAGCCAATGGCCTCTGT GGGTTCTGTGCCTGGAAATGGAGAGATCTGAGTACAGCCTGCTTTGAATGGCCCTGT GAGGCAACCCCAAAGCAAGGGGGTCCAGGTATACTATGGGCCCAGCACCTAAAGCCA CCCTTGGGAGATGATACTCAGGTGGGAAATTCGTAGACTGGGGGACTGAACCAATCC CAAGATCTGGAAAAGTTTTGATGAAGACTTGAAAAGCTCCTAGCTTCGGGGGTCTGG GAAGCATGAGCACTTACCAGGCAAAAGCTCCGTGAGCGTATCTGCTGTCCTTCTGCA TGCCCAGGTACCTCAGTTTTTTTCAACAGCAAGGAAACTAGGGCAATAAAGGGAACC AGCAGAGCTAGAGCCACCCACACATCCAGGGGGGCACTTGACTCTCCCTACTCCTCC TAGGAACCAAAAGGACAAAGTCCATGTTGACAGCAGGGAAGGAAAGGGGGATATAAC CTTGACGCAAACCAACACTGGGGTGTTAGAATCTCCTCATTCACTCTGTCCTGGAGT TGGGTTCTGGCTCTCCTTCACACCTAGGACTCTGAAATGAGCAAGCACTTCAGACAG TCAGGGTAGCAAGAGTCTAGCTGTCTGGTGGGCACCCAAAATGACCAGGGCTTAAGT CCCTTTCCTTTGGTTTAAGCCCGTTATAATTAAATGGTACCAAAAGCTTTAA(SEQ IDNO:191) >NP_032824.1programmedcelldeathprotein1precursor [Musmusculus] MWVRQVPWSFTWAVLQLSWQSGWLLEVPNGPWRSLTFYPAWLTVSEGANATFTCSLS NWSEDLMLNWNRLSPSNQTEKQAAFCNGLSQPVQDARFQIIQLPNRHDFHMNILDTR RNDSGIYLCGAISLHPKAKIEESPGAELVVTERILETSTRYPSPSPKPEGRFQGMVI GIMSALVGIPVLLLLAWALAVFCSTSMSEARGAGSKDDTLKEEPSAAPVPSVAYEEL DFQGREKTPELPTACVHTEYATIVFTEGLGASAMGRRGSADGLQGPRPPRHEDGHCS WPL(SEQIDNO:191) mScarlet >KY021423.1SyntheticconstructmScarletgene,partial cds,mRNA ATGGTGAGCAAGGGCGAGGCAGTGATCAAGGAGTTCATGCGGTTCAAGGTGCACATG GAGGGCTCCATGAACGGCCACGAGTTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCC TACGAGGGCACCCAGACCGCCAAGCTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTC TCCTGGGACATCCTGTCCCCTCAGTTCATGTACGGCTCCAGGGCCTTCACCAAGCAC CCCGCCGACATCCCCGACTACTATAAGCAGTCCTTCCCCGAGGGCTTCAAGTGGGAG CGCGTGATGAACTTCGAGGACGGCGGCGCCGTGACCGTGACCCAGGACACCTCCCTG GAGGACGGCACCCTGATCTACAAGGTGAAGCTCCGCGGCACCAACTTCCCTCCTGAC GGCCCCGTAATGCAGAAGAAGACAATGGGCTGGGAAGCGTCCACCGAGCGGTTGTAC CCCGAGGACGGCGTGCTGAAGGGCGACATTAAGATGGCCCTGCGCCTGAAGGACGGC GGCCGCTACCTGGCGGACTTCAAGACCACCTACAAGGCCAAGAAGCCCGTGCAGATG CCCGGCGCCTACAACGTCGACCGCAAGTTGGACATCACCTCCCACAACGAGGACTAC ACCGTGGTGGAACAGTACGAACGCTCCGAGGGCCGCCACTCCACCGGCGGCATGGAC GAGCTGTACAAG(SEQIDNO:192) >APD76535.1mScarlet,partial[syntheticconstruct] MVSKGEAVIKEFMRFKVHMEGSMNGHEFEIEGEGEGRPYEGTQTAKLKVTKGGPLPF SWDILSPQFMYGSRAFTKHPADIPDYYKQSFPEGFKWERVMNFEDGGAVTVTQDTSL EDGTLIYKVKLRGTNFPPDGPVMQKKTMGWEASTERLYPEDGVLKGDIKMALRLKDG GRYLADFKTTYKAKKPVQMPGAYNVDRKLDITSHNEDYTVVEQYERSEGRHSTGGMD ELYK(SEQIDNO:193) Nanoluciferase >JQ513379.1NanoLucreportervectorpNL1.1.CMV [Nluc/CMV],completesequence,mRNA GGCCTAACTGGCCTCAATATTGGCCATTAGCCATATTATTCATTGGTTATATAGCAT AAATCAATATTGGCTATTGGCCATTGCATACGTTGTATCTATATCATAATATGTACA TTTATATTGGCTCATGTCCAATATGACCGCCATGTTGGCATTGATTATTGACTAGTT ATTAATAGTAATCAATTACGGGGTCATTAGTTCATAGCCCATATATGGAGTTCCGCG TTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCAT TGACGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGAC GTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATC ATATGCCAAGTCCGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATT ATGCCCAGTACATGACCTTACGGGACTTTCCTACTTGGCAGTACATCTACGTATTAG TCATCGCTATTACCATGGTGATGCGGTTTTGGCAGTACACCAATGGGCGTGGATAGC GGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGT TTTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAATAACCCCGCCCCGTTGA CGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTTTAG TGAACCGTCAGATCACTAGAAGCTTTATTGCGGTAGTTTATCACAGTTAAATTGCTA ACGCAGTCAGTGGGCCTCGGCGGCCAAGCTTGGCAATCCGGTACTGTTGGTAAAGCC ACCATGGTCTTCACACTCGAAGATTTCGTTGGGGACTGGCGACAGACAGCCGGCTAC AACCTGGACCAAGTCCTTGAACAGGGAGGTGTGTCCAGTTTGTTTCAGAATCTCGGG GTGTCCGTAACTCCGATCCAAAGGATTGTCCTGAGCGGTGAAAATGGGCTGAAGATC GACATCCATGTCATCATCCCGTATGAAGGTCTGAGCGGCGACCAAATGGGCCAGATC GAAAAAATTTTTAAGGTGGTGTACCCTGTGGATGATCATCACTTTAAGGTGATCCTG CACTATGGCACACTGGTAATCGACGGGGTTACGCCGAACATGATCGACTATTTCGGA CGGCCGTATGAAGGCATCGCCGTGTTCGACGGCAAAAAGATCACTGTAACAGGGACC CTGTGGAACGGCAACAAAATTATCGACGAGCGCCTGATCAACCCCGACGGCTCCCTG CTGTTCCGAGTAACCATCAACGGAGTGACCGGCTGGCGGCTGTGCGAACGCATTCTG GCGTAATTCTAGAGTCGGGGCGGCCGGCCGCTTCGAGCAGACATGATAAGATACATT GATGAGTTTGGACAAACCACAACTAGAATGCAGTGAAAAAAATGCTTTATTTGTGAA ATTTGTGATGCTATTGCTTTATTTGTAACCATTATAAGCTGCAATAAACAAGTTAAC AACAACAATTGCATTCATTTTATGTTTCAGGTTCAGGGGGAGGTGTGGGAGGTTTTT TAAAGCAAGTAAAACCTCTACAAATGTGGTAAAATCGATAAGGATCCGTCGACCGAT GCCCTTGAGAGCCTTCAACCCAGTCAGCTCCTTCCGGTGGGCGCGGGGCATGACTAT CGTCGCCGCACTTATGACTGTCTTCTTTATCATGCAACTCGTAGGACAGGTGCCGGC AGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGC GAGCGGTATCAGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATA ACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGG CCGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATC GACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTC CCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGATACC TGTCCGCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGT ATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCG TTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTAA GACACGACTTATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGT ATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGCCTAACTACGGCTACACTAGAA GAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTG GTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCA AGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCTTTTCTA CGGGGTCTGACGCTCAGTGGAACGAAAACTCACGTTAAGGGATTTTGGTCATGAGAT TATCAAAAAGGATCTTCACCTAGATCCTTTTAAATTAAAAATGAAGTTTTAAATCAA TCTAAAGTATATATGAGTAAACTTGGTCTGACAGCGGCCGCAAATGCTAAACCACTG CAGTGGTTACCAGTGCTTGATCAGTGAGGCACCGATCTCAGCGATCTGCCTATTTCG TTCGTCCATAGTGGCCTGACTCCCCGTCGTGTAGATCACTACGATTCGTGAGGGCTT ACCATCAGGCCCCAGCGCAGCAATGATGCCGCGAGAGCCGCGTTCACCGGCCCCCGA TTTGTCAGCAATGAACCAGCCAGCAGGGAGGGCCGAGCGAAGAAGTGGTCCTGCTAC TTTGTCCGCCTCCATCCAGTCTATGAGCTGCTGTCGTGATGCTAGAGTAAGAAGTTC GCCAGTGAGTAGTTTCCGAAGAGTTGTGGCCATTGCTACTGGCATCGTGGTATCACG CTCGTCGTTCGGTATGGCTTCGTTCAACTCTGGTTCCCAGCGGTCAAGCCGGGTCAC ATGATCACCCATATTATGAAGAAATGCAGTCAGCTCCTTAGGGCCTCCGATCGTTGT CAGAAGTAAGTTGGCCGCGGTGTTGTCGCTCATGGTAATGGCAGCACTACACAATTC TCTTACCGTCATGCCATCCGTAAGATGCTTTTCCGTGACCGGCGAGTACTCAACCAA GTCGTTTTGTGAGTAGTGTATACGGCGACCAAGCTGCTCTTGCCCGGCGTCTATACG GGACAACACCGCGCCACATAGCAGTACTTTGAAAGTGCTCATCATCGGGAATCGTTC TTCGGGGCGGAAAGACTCAAGGATCTTGCCGCTATTGAGATCCAGTTCGATATAGCC CACTCTTGCACCCAGTTGATCTTCAGCATCTTTTACTTTCACCAGCGTTTCGGGGTG TGCAAAAACAGGCAAGCAAAATGCCGCAAAGAAGGGAATGAGTGCGACACGAAAATG TTGGATGCTCATACTCGTCCTTTTTCAATATTATTGAAGCATTTATCAGGGTTACTA GTACGTCTCTCAAGGATAAGTAAGTAATATTAAGGTACGGGAGGTATTGGACAGGCC GCAATAAAATATCTTTATTTTCATTACATCTGTGTGTTGGTTTTTTGTGTGAATCGA TAGTACTAACATACGCTCTCCATCAAAACAAAACGAAACAAAACAAACTAGCAAAAT AGGCTGTCCCCAGTGCAAGTGCAGGTGCCAGAACATTTCTCT(SEQIDNO: 194) >AFJ15599.1NanoLucluciferase[NanoLucreportervector pNL1.1.CMV[Nluc/CMV]] MVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPIQRIVLSGENGLKID IHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFKVILHYGTLVIDGVTPNMIDYFGR PYEGIAVFDGKKITVTGTLWNGNKIIDERLINPDGSLLFRVTINGVTGWRLCERILA (SEQIDNO:195)
[0115] The polypeptides provided in Table 1 above are involved in a range of biological processes, including but not limited to, suppressing the adaptive arm of the immune system (e.g., PD-L1); cellular adhesion (e.g., nectin), immune activation (e.g., HVEM), and the like. The POI domains can also be used to track, purify, or identify the engineered EVs from native EVs (e.g., mScarlet and nanoluciferase). The genes, transcripts, polypeptides, and variants thereof can be used in any combination from Table 1 to be expressed by an engineered EV provided herein. In some embodiments, the POI domain is the human polypeptide. In some embodiments, the POI domain is a homologue of the human polypeptide (e.g., mouse).
[0116] In some embodiments of any of the aspects, the engineered cell or EV provided herein comprises an exogenous nucleic acid encoding one or more exogenous polypeptide(s) selected from the group consisting of: the polypeptides listed in Table 1.
[0117] In some embodiments of any of the aspects, the POI domain is PD-L1 or a fragment thereof. In some embodiments of any of the aspects, the POI domain is PD-L2 or a fragment thereof. In some embodiments of any of the aspects, the POI domain is FGL1 or a fragment thereof. In some embodiments of any of the aspects, the POI domain is 4-1BBL or a fragment thereof. In some embodiments of any of the aspects, the POI domain is CTLA or a fragment thereof.
[0118] In some embodiments of any of the aspects, the POI domain substantially binds to one or more of a target polypeptide. In some embodiments of any of the aspects, the target polypeptide is a cellular receptor. In some embodiments of any of the aspects, the target polypeptide is an immunosuppressive polypeptide. In some embodiments of any of the aspects, the target polypeptide is an immunostimulatory polypeptide. The engineered exosomes provided herein can be designed to activate, block, or modulate a given target polypeptide with the appropriate POI domain that binds to or modulates the function or expression of the target polypeptide. Non-limiting examples of target polypeptides include those listed in Table 2 (below).
TABLE-US-00002 TABLE 2 Exemplary Target Polypeptides PD-1 VISTA LAG-3 CD44 CD80 BTLA CD112 IL10RA CD86 CD160 CD200R IL10RB CD28 HVEM CD200 Tim-3 ICOS CD2 Galectin 9 TNFRSF25 CD28H SLAM TIM-3 TNFRSF6B CD150 PD-L1 CD58 CD226 CD113 CTLA-4 TIM-1 CD155 CD27 4-1BB (CD137) TIM-4 CD112 CD30 GITR CD40 DR3 LFA-3 (CD58) CD27L CD30L GITRL CD40L CD48 CD244 DcR3 CD28H LFA-3 (CD58) CD98 TNF Receptor TNF receptor Superfamily associated members factor (TRAF) family members Butyrophilin PD-L2 Nectin TIM family family members members B7/CD28 family SLAM family Nectin-like Collagen family members members binding receptors proteins LAIR-1 (CD305)
[0119] The EVs provided herein further comprise at least one fusion protein comprising a vesicle targeting domain. In various embodiments, the vesicle targeting domain provided herein is capable of binding or anchoring the fusion polypeptide provided herein to an extracellular vesicle, e.g., via targeting of the phospholipid bilayer membrane. In various embodiments, the vesicle targeting domain is a GPI domain (i.e., GPI linker, GPI anchor), fatty acetylation site, or prenylation site. One of skill in the art can appreciate that the aforementioned refer to peptide or protein sites, wherein covalent lipid attachment supports embedding of the lipid in a cell membrane (i.e., phospholipid bilayer). Biochemical forces that anchor EV targeting domains to the EV phospholipid bilayer may include, but are not limited to, electrostatic forces, affinity for EVs through protein-protein interactions with natively resident proteins (e.g., CD81, CD63, CD9, ALIX, TSG101. CD98, CD298, MARCKS, PTGFRN, Lactadherin (MFGe8)), association or affinity for negatively or positively curved phospholipids, association or affinity for negatively or positively charged domains of resident membrane associated proteins, etc., or the like.
[0120] Additional non-limiting examples of membrane targeting domains that can be used and their properties are further described in detail, e.g., Alberts B, Johnson A, Lewis J, et al., Molecular Biology of the Cell, 4th edition, New York: Garland Science, 2002. Membrane Proteins, https://www.ncbi.nlm.nih.gov/books/NBK26878/; Marilyn D. Resh, Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochimica et Biophysica Acta (BBA)Molecular Cell Research. Volume 1451, Issue 1, 12 Aug. 1999, Pages 1-16, doi.org/10.1016/S0167-4889(99)00075-0; Ann Apolloni, et. al., H-ras but Not K-ras Traffics to the Plasma Membrane through the Exocytic Pathway, Molecular and Cellular Biology April 2000, 20 (7) 2475-2487, DOI: 10.1128/MCB.20.7.2475-2487.2000; Rosie Dawaliby et. al., Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells, Membrane Biology, VOLUME 291, ISSUE 7, doi.org/10.1074/jbc.M115.706523; R. J. Deschenes, Protein Palmitoylation, Encyclopedia of Biological Chemistry (Second Edition), Academic Press, 2013, Pages 645-647, ISBN 9780123786319, https://doi.org/10.1016/B978-0-12-378630-2.00022-0.; Charuta C. Palsuledesai and Mark D. Distefano, Protein Prenylation: Enzymes, Therapeutics, and Biotechnology Applications, ACS Chemical Biology 2015 10 (1), 51-62, DOI: 10.1021/cb500791f; Hung M E, Leonard J N. Stabilization of exosome-targeting peptides via engineered glycosylation, J Biol Chem, 2015 Mar. 27; 290(13):8166-72, doi: 10.1074/jbc.M114.621383; Udenwobele Daniel Ikenna, et. al., Myristoylation: An Important Protein Modification in the Immune Response, Frontiers in Immunology, Vol:8, 2017, DOI=10.3389/fimmu.2017.00751; Kinoshita Taroh 2020 Biosynthesis and biology of mammalian GPI-anchored proteins Open Biol. 10190290, http://doi.org/10.1098/rsob.190290, the contents of which are incorporated herein by reference in their entireties.
[0121] In some embodiments, the fusion polypeptide comprises one or more, two or more, three or more, four or more, five or more, or six or more vesicle targeting domains on the same polypeptide or nucleic acid construct encoding said polypeptide. For example, the fusion polypeptides provided herein can comprise PD-L1 and Glycosylphosphatidylinositol (GPI).
[0122] In some embodiments, the vesicle targeting domain is a prenylated protein. Prenylated proteins are proteins that have at least one prenylation site. Prenylation occurs when a 15-carbon or 20-carbon, farnesyl or geranylgeranyl isoprenoid, respectively, is covalently bound via a thioether bond to a cysteine at or near the carboxy terminus of a protein. In general, a prenylation site comprises an amino acid sequence CAAX, wherein C represents cysteine, A represents an aliphatic amino acid (glycine, alanine, valine, leucine, or isoleucine), and X represents alanine, methionine, serine, leucine, or glutamine.
[0123] In some embodiments, the vesicle targeting domain is a fatty acylated protein. Fatty acylated proteins are proteins that have been modified post-translationally by covalent attachment of one or more fatty acids, generally with a saturated fatty acid that comprises 14-carbon (e.g., myristic acid) via myristoylation or 16-carbons (e.g., palmitic acid) via palmitoylation. For example, proteins destined to become myristoylated begin with the amino acids Met-Gly-X-X-X followed by a serine or threonine at position 6 and lysine or arginine at position 7 and/or 8 wherein X can be any amino acid. The methionine is removed and a myristate is linked to the glycine via an amide bond. Palmitoylation herein means a posttranslational covalent attachment of fatty acids (e.g., palmitic acid) to cysteine (S-palmitoylation), serine and/or threonine (O-palmitoylation), and to the amino group of lysine (N-palmitoylation) of proteins.
[0124] Palmitoylated proteins may be acylated by attachment of a thioester linkage to a sulfhydryl group of cysteine, or via a palmitate linked to the amino group of an N-terminal cysteine. Palmitoylation sites may be present near the N- or C-terminus of a protein.
[0125] In some embodiments, the vesicle targeting domain is a glycosylphosphatidylinositol (GPI) anchor. A glycosylphosphatidylinositol (GPI) anchor (GPI anchor) or GPI sticky binder are used interchangeably and refer to a means of stably anchoring a protein to an outer leaflet (e.g., exterior layer of a phospholipid bilayer) of a cell membrane. A GPI anchor comprises a glycan, a phosphoethanolamine linker, a phospholipid tail, and may be modified by various glycan sidechains. The glycan core comprises phosphoinositol, glucosamine, and mannose residues wherein said mannose residues may be modified for example with phosphoethanolamine or carbohydrates. The phosphoethanolamine is amide-bonded to the carboxyl terminus of a protein during the process of GPI attachment. In some embodiments, the vesicle targeting domain may have affinity to EV resident proteins, e.g., CD81, CD63, CD9, ALIX, TSG101, CD98, CD298, MARCKS, PTGFRN, Lactadherin (MFGe8)
[0126] Sticky binders can include a sequence for one or more myristoylation and/or palmitoylation (Myr/Palm) sites fused to a transmembrane domain from 4F2 (CD98). For example, the myristoylation sequence from the MARCKS protein may be modified to encode for one or more myristoylation and palmitoylation sites, wherein the modified MARCKS protein sequence is fused to a protein sequence of the transmembrane domain from 4F2 via a covalent peptide bond. A Myr/Palm followed by the 4F2 transmembrane domain can improve loading of the fusion proteins provided herein when compared with 4F2 transmembrane domain alone or Myr/Palm alone.
[0127] Non-limiting examples of vesicle targeting domains that enhance fusion polypeptide structure and function on the extracellular vesicles are provided in Table 3 (below).
TABLE-US-00003 TABLE3 ExosomeTargetingDomain ExosomeTargeting Domain/Sticky NucleicAcidSequence(SEQIDNO:) Binder AminoAcidSequence(SEQIDNO:) HumanCD55(DAF) >NM_000574.5HomosapiensCD55molecule(Cromerblood Glycosylphos group)(CD55),transcriptvariant1,mRNA phatidylinositol CTGCTTACTGCAACTCGCTCCGGCCGCTGGGCGTAGCTGCGACTCGGCGGAGTCCCG (GPI) GCGGCGCGTCCTTGTTCTAACCCGGCGCGCCATGACCGTCGCGCGGCCGAGCGTGCC CGCGGCGCTGCCCCTCCTCGGGGAGCTGCCCCGGCTGCTGCTGCTGGTGCTGTTGTG CCTGCCGGCCGTGTGGGGTGACTGTGGCCTTCCCCCAGATGTACCTAATGCCCAGCC AGCTTTGGAAGGCCGTACAAGTTTTCCCGAGGATACTGTAATAACGTACAAATGTGA AGAAAGCTTTGTGAAAATTCCTGGCGAGAAGGACTCAGTGATCTGCCTTAAGGGCAG TCAATGGTCAGATATTGAAGAGTTCTGCAATCGTAGCTGCGAGGTGCCAACAAGGCT AAATTCTGCATCCCTCAAACAGCCTTATATCACTCAGAATTATTTTCCAGTCGGTAC TGTTGTGGAATATGAGTGCCGTCCAGGTTACAGAAGAGAACCTTCTCTATCACCAAA ACTAACTTGCCTTCAGAATTTAAAATGGTCCACAGCAGTCGAATTTTGTAAAAAGAA ATCATGCCCTAATCCGGGAGAAATACGAAATGGTCAGATTGATGTACCAGGTGGCAT ATTATTTGGTGCAACCATCTCCTTCTCATGTAACACAGGGTACAAATTATTTGGCTC GACTTCTAGTTTTTGTCTTATTTCAGGCAGCTCTGTCCAGTGGAGTGACCCGTTGCC AGAGTGCAGAGAAATTTATTGTCCAGCACCACCACAAATTGACAATGGAATAATTCA AGGGGAACGTGACCATTATGGATATAGACAGTCTGTAACGTATGCATGTAATAAAGG ATTCACCATGATTGGAGAGCACTCTATTTATTGTACTGTGAATAATGATGAAGGAGA GTGGAGTGGCCCACCACCTGAATGCAGAGGAAAATCTCTAACTTCCAAGGTCCCACC AACAGTTCAGAAACCTACCACAGTAAATGTTCCAACTACAGAAGTCTCACCAACTTC TCAGAAAACCACCACAAAAACCACCACACCAAATGCTCAAGCAACACGGAGTACACC TGTTTCCAGGACAACCAAGCATTTTCATGAAACAACCCCAAATAAAGGAAGTGGAAC CACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTT GCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAGCCAAAGAAGAGTTAAGAAGA AAATACACACAAGTATACAGACTGTTCCTAGTTTCTTAGACTTATCTGCATATTGGA TAAAATAAATGCAATTGTGCTCTTCATTTAGGATGCTTTCATTGTCTTTAAGATGTG TTAGGAATGTCAACAGAGCAAGGAGAAAAAAGGCAGTCCTGGAATCACATTCTTAGC ACACCTACACCTCTTGAAAATAGAACAACTTGCAGAATTGAGAGTGATTCCTTTCCT AAAAGTGTAAGAAAGCATAGAGATTTGTTCGTATTTAGAATGGGATCACGAGGAAAA GAGAAGGAAAGTGATTTTTTTCCACAAGATCTGTAATGTTATTTCCACTTATAAAGG AAATAAAAAATGAAAAACATTATTTGGATATCAAAAGCAAATAAAAACCCAATTCAG TCTCTTCTAAGCAAAATTGCTAAAGAGAGATGAACCACATTATAAAGTAATCTTTGG CTGTAAGGCATTTTCATCTTTCCTTCGGGTTGGCAAAATATTTTAAAGGTAAAACAT GCTGGTGAACCAGGGGTGTTGATGGTGATAAGGGAGGAATATAGAATGAAAGACTGA ATCTTCCTTTGTTGCACAAATAGAGTTTGGAAAAAGCCTGTGAAAGGTGTCTTCTTT GACTTAATGTCTTTAAAAGTATCCAGAGATACTACAATATTAACATAAGAAAAGATT ATATATTATTTCTGAATCGAGATGTCCATAGTCAAATTTGTAAATCTTATTCTTTTG TAATATTTATTTATATTTATTTATGACAGTGAACATTCTGATTTTACATGTAAAACA AGAAAAGTTGAAGAAGATATGTGAAGAAAAATGTATTTTTCCTAAATAGAAATAAAT GATCCCATTTTTTGGTATCATGTAGTATGTGAAATTTATTCTTAAACGTGACTACTT TATTTCTAAATAAGAAATTCCCTACCTGCTTCCTACAAGCAGTTCAGAATGCCATGC CTTGGTTGTCCTAGTGTGAATAATTTTCAGCTACTTTAAAATTATATTGTACTTTCT CAAGCATGTCATATCCTTTCCTATTAGAGTATCTATATTACTTGTTACTGATTTACC TGAAGGCAATCTGATTAATTTCTAGGTTTTTACCATATTCTTGTCATCTTGCCAATT ACATTTTAAGTGTTAGACTAGACTAAGATGTACTAGTTGTATAGAATATAACTAGA TTTATTATGGCAATGTTTATTTTGTCATTTTGCTTCATCTGTTTTGTTGTTGAAGTA CTTTAAATTTCATACGTTCATGGCATTTCACTGTAAAGACTTTAATGTGTATTTCTT AAAATAAAACTTTTTTTCCTCCTTAA(SEQIDNO:196) >NP_000565.1complementdecay-acceleratingfactorisoform 1preproprotein[Homosapiens] MTVARPSVPAALPLLGELPRLLLLVLLCLPAVWGDCGLPPDVPNAQPALEGRTSFPE DTVITYKCEESFVKIPGEKDSVICLKGSQWSDIEEFCNRSCEVPTRLNSASLKQPYI TNYFPVGTVVEYECRPGYRREPSLSPKLTCLQNLKWSTAVEFCKKKSCPNPGEIRN GQIDVPGGILFGATISFSCNTGYKLFGSTSSFCLISGSSVQWSDPLPECREIYCPAP PQIDNGIIQGERDHYGYRQSVTYACNKGFTMIGEHSIYCTVNNDEGEWSGPPPECRG KSLTSKVPPTVQKPTTVNVPTTEVSPTSQKTTTKTTTPNAQATRSTPVSRTTKHEHE TTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT(SEQIDNO:197) HumanCD59 >NM_203330.2HomosapiensCD59molecule(CD59blood Glycosylphos- group)(CD59),transcriptvariant1,mRNA phatidylinositol GGGGCCGGGGGGCGGAGCCTTGCGGGCTGGAGCGAAAGAATGCGGGGGCTGAGCGCA (GPI) GAAGCGGCTCGAGGCTGGAAGAGGATCTTGGGCGCCGCCAGTCTCTCTCTGTTGCCC AAGCTGGAGTGCAGTGGCACAGTCTTGGCTCACTGCAACCTCCACCTCCTGGGTGCA AGCGATTCTCGTGTCTCAGCCTCTCAAGTAGCTGGGATTACAGTCTTTAGCACCAGT TGGTGTAGGAGTTGAGACCTACTTCACAGTAGTTCTGTGGACAATCACAATGGGAAT CCAAGGAGGGTCTGTCCTGTTCGGGCTGCTGCTCGTCCTGGCTGTCTTCTGCCATTC AGGTCATAGCCTGCAGTGCTACAACTGTCCTAACCCAACTGCTGACTGCAAAACAGC CGTCAATTGTTCATCTGATTTTGATGCGTGTCTCATTACCAAAGCTGGGTTACAAGT GTATAACAAGTGTTGGAAGTTTGAGCATTGCAATTTCAACGACGTCACAACCCGCTT GAGGGAAAATGAGCTAACGTACTACTGCTGCAAGAAGGACCTGTGTAACTTTAACGA ACAGCTTGAAAATGGTGGGACATCCTTATCAGAGAAAACAGTTCTTCTGCTGGTGAC TCCATTTCTGGCAGCAGCCTGGAGCCTTCATCCCTAAGTCAACACCAGGAGAGCTTC TCCCAAACTCCCCGTTCCTGCGTAGTCCGCTTTCTCTTGCTGCCACATTCTAAAGGC TTGATATTTTCCAAATGGATCCTGTTGGGAAAGAATAAAATTAGCTTGAGCAACCTG GCTAAGATAGAGGGGCTCTGGGAGACTTTGAAGACCAGTCCTGTTTGCAGGGAAGCC CCACTTGAAGGAAGAAGTCTAAGAGTGAAGTAGGTGTGACTTGAACTAGATTGCATG CTTCCTCCTTTGCTCTTGGGAAGACCAGCTTTGCAGTGACAGCTTGAGTGGGTTCTC TGCAGCCCTCAGATTATTTTTCCTCTGGCTCCTTGGATGTAGTCAGTTAGCATCATT AGTACATCTTTGGAGGGTGGGGCAGGAGTATATGAGCATCCTCTCTCACATGGAACG CTTTCATAAACTTCAGGGATCCCGTGTTGCCATGGAGGCATGCCAAATGTTCCATAT GTGGGTGTCAGTCAGGGACAACAAGATCCTTAATGCAGAGCTAGAGGACTTCTGGCA GGGAAGTGGGGAAGTGTTCCAGATAGCAGGGCATGAAAACTTAGAGAGGTACAAGTG GCTGAAAATCGAGTTTTTCCTCTGTCTTTAAATTTTATATGGGCTTTGTTATCTTCC ACTGGAAAAGTGTAATAGCATACATCAATGGTGTGTTAAAGCTATTTCCTTGCCTTT TTTTTATTGGAATGGTAGGATATCTTGGCTTTGCCACACACAGTTACAGAGTGAACA CTCTACTACATGTGACTGGCAGTATTAAGTGTGCTTATTTTAAATGTTACTGGTAGA AAGGCAGTTCAGGTATGTGTGTATATAGTATGAATGCAGTGGGGACACCCTTTGTGG TTACAGTTTGAGACTTCCAAAGGTCATCCTTAATAACAACAGATCTGCAGGGGTATG TTTTACCATCTGCATCCAGCCTCCTGCTAACTCCTAGCTGACTCAGCATAGATTGTA TAAAATACCTTTGTAACGGCTCTTAGCACACTCACAGATGTTTGAGGCTTTCAGAAG CTCTTCTAAAAAATGATACACACCTTTCACAAGGGCAAACTTTTTCCTTTTCCCTGT GTATTCTAGTGAATGAATCTCAAGATTCAGTAGACCTAATGACATTTGTATTTTATG ATCTTGGCTGTATTTAATGGCATAGGCTGACTTTTGCAGATGGAGGAATTTCTTGAT TAATGTTGAAAAAAAACCCTTGATTATACTCTGTTGGACAAACCGAGTGCAATGAAT GATGCTTTTCTGAAAATGAAATATAACAAGTGGGTGAATGTGGTTATGGCCGAAAAG GATATGCAGTATGCTTAATGGTAGCAACTGAAAGAAGACATCCTGAGCAGTGCCAGC TTTCTTCTGTTGATGCCGTTCCCTGAACATAGGAAAATAGAAACTTGCTTATCAAAA CTTAGCATTACCTTGGTGCTCTGTGTTCTCTGTTAGCTCAGTGTCTTTCCTTACATC AATAGGTTTTTTTTTTTTTTTTTGGCCTGAGGAAGTACTGACCATGCCCACAGCCAC CGGCTGAGCAAAGAAGCTCATTTCATGTGAGTTCTAAGGAATGAGAAACAATTTTGA TGAATTTAAGCAGAAAATGAATTTCTGGGAACTTTTTTGGGGGCGGGGGGGTGGGGA ATTCAGCCACACTCCAGAAAGCCAGGAGTCGACAGTTTTGGAAGCCTCTCTCAGGAT TGAGATTCTAGGATGAGATTGGCTTACTGCTATCTTGTGTCATGTACCCACTTTTTG GCCAGACTACACTGGGAAGAAGGTAGTCCTCTAAAGCAAAATCTGAGTGCCACTAAA TGGGGAGATGGGGCTGTTAAGCTGTCCAAATCAACAAGGGTCATATAAATGGCCTTA AACTTTGGGGTTGCTTTCTGCAAAAAGTTGCTGTGACTCATGCCATAGACAAGGTTG AGTGCCTGGACCCAAAGGCAATACTGTAATGTAAAGACATTTATAGTACTAGGCAAA CAGCACCCCAGGTACTCCAGGCCCTCCTGGCTGGAGAGGGCTGTGGCAATAGAAAAT TAGTGCCAACTGCAGTGAGTCAGCCTAGGTTAAATAGAGAGTGTAAGAGTGCTGGAC AGGAACCTCCACCCTCATGTCACATTTCTTCAATGTGACCCTTCTGGCCCCTCTCCT CCTGACAGCGGAACAATGACTGCCCCGATAGGTGAGGCTGGAGGAAGAATCAGTCCT GTCCTTGGCAAGCTCTTCACTATGACAGTAAAGGCTCTCTGCCTGCTGCCAAGGCCT GTGACTTTCTAACCTGGCCTCACGCTGGGTAAGCTTAAGGTAGAGGTGCAGGATTAG CAAGCCCACCTGGCTACCAGGCCGACAGCTACATCCTCCAACTGACCCTGATCAACG AAGAGGGATTCATGTGTCTGTCTCAGTTGGTTCCAAATGAAACCAGGGAGCAGGGGA GTTAGGAATCGAACACCAGTCATGCCTACTGGCTCTCTGCTCGAGAGCCAATACCCT GTGCCCTCCACTCATCTGGATTTACAGGAACTGTCATAGTGTTCAGTATTGGGTGGT GATAAGCCCATTGGATTGTCCCCTTGGGGGGATGAGCTAGGGGTGCAAGGAACACCT GATGAGTAGATAAGTGGAGCTCATGGTATTTCCTGAAAGATGCTAATCTATTTGCCA AACTTGGTCTTGAATGTACTGGGGGCTTCAAGGTATGGGTATATTTTTCTTGTGTCC TTGCAGTTAGCCCCCATGTCTTATGTGTGTCCTGAAAAAATAAGAGCCTGCCCAAGA CTTTGGGCCTCTTGACAGAATTAACCACTTTTATACATCTGAGTTCTCTTGGTAAGT TCTTTAGCAGTGTTCAAAGTCTACTAGCTCGCATTAGTTTCTGTTGCTGCCAACAGA TCTGAACTAATGCTAACAGATCCCCCTGAGGGATTCTTGATGGGCTGAGCAGCTGGC TGGAGCTAGTACTGACTGACATTCATTGTGATGAGGGCAGCTTTCTGGTACAGGATT CTAAGCTCTATGTTTTATATACATTTTCATCTGTACTTGCACCTCACTTTACACAAG AGGAAACTATGCAAAGTTAGCTGGATCGCTCAAGGTCACTTAGGTAAGTTGGCAAGT CCATGCTTCCCACTCAGCTCCTCAGGTCAGCAAGTCTACTTCTCTGCCTATTTTGTA TACTCTCTTTAATATGTGCCTAGCTTTGGAAAGTCTAGAATGGGTCCCTGGTGCCTT TTTACTTTGAAGAAATCAGTTTCTGCCTCTTTTTGGAAAAGAAAACAAAGTGCAATT GTTTTTTACTGGAAAGTTACCCAATAGCATGAGGTGAACAGGACGTAGTTAGGCCTT CCTGTAAACAGAAAATCATATCAAAACACTATCTTCCCATCTGTTTCTCAATGCCTG CTACTTCTTGTAGATATTTCATTTCAGGAGAGCAGCAGTTAAACCCGTGGATTTTGT AGTTAGGAACCTGGGTTCAAACCCTCTTCCACTAATTGGCTATGTCTCTGGACAAGT TTTTTTTTTTTTTTTTTTTTAAACCCTTTCTGAACTTTCACTTTCTATGTCTACCTC AAAGAATTGTTGTGAGGCTTGAGATAATGCATTTGTAAAGGGTCTGCCAGATAGGAA GATGCTAGTTATGGATTTACAAGGTTGTTAAGGCTGTAAGAGTCTAAAACCTACAGT GAATCACAATGCATTTACCCCCACTGACTTGGACATAAGTGAAAACTAGCCAGAAGT CTCTTTTTCAAATTACTTACAGGTTATTCAATATAAAATTTTTGTAATGGATAATCT TATTTATCTAAACTAAAGCTTCCTGTTTATACACACTCCTGTTATTCTGGGATAAGA TAAATGACCACAGTACCTTAATTTCTAGGTGGGTGCCTGTGATGGTTCATTGTAGGT AAGGACATTTTCTCTTTTTCAGCAGCTGTGTAGGTCCAGAGCCTCTGGGAGAGGAGG GGGGTAGCATGCACCCAGCAGGGGACTGAACTGGGAAACTCAAGGTTCTTTTTACTG TGGGGTAGTGAGCTGCCTTTCTGTGATCGGTTTCCCTAGGGATGTTGCTGTTCCCCT CCTTGCTATTCGCAGCTACATACAACGTGGCCAACCCCAGTAGGCTGATCCTATATA TGATCAGTGCTGGTGCTGACTCTCAATAGCCCCACCCAAGCTGGCTATAGGTTTACA GATACATTAATTAGGCAACCTAAAATATTGATGCTGGTGTTGGTGTGACATAATGCT ATGGCCAGAACTGAAACTTAGAGTTATAATTCATGTATTAGGGTTCTCCAGAGGGAC AGAATTAGTAGGATATATGTATATATGAAAGGGAGGTTATTAGGGAGAACTGGCTCC CACAGTTAGAAGGCGAAGTCGCACAATAGGCCGTCTGCAAGCTGGGTTAGAGAGAAG CCAGTAGTGGCTCAGCCTGAGTTCAAAAACCTCAAAACTGGGGAAGCTGACAGTGCA GCCAGCCTTCAGTCTGTGGCCAAAGGCCCAAGAGCCCCTGGCAACCAACCCACTGGT GCAAGTCCTAGATTCCAAAGGCTGAAGAACCTGGAGTCTGATGTCCAAGAGCAGGAA GAGTGGAAGAAAGCCAGAAGACTCAGCAAACAAGGTAGACAGTGTCTACCACCATAG TGGCCATACCAAAGAGGCTACCGATTCCTTCCTGCTACCTGGATCCCTGAAGTTGCC CTGGTCTCTGCACCTTCTAAACCTAGTTCTTAAGAGCTTTCCATTACATGAGCTGTC TCAAAGCCCTCCAATAAATTCTCAGTGTAAGCTTCTGTTGCTTGTGGACAGAAAATT CTGACAGACCTACCCTATAAGTGTTACTGTCAGGATAACATGAGAACGCACAACAGT AAGTGGTCACTAAGTGTTAGCTACGGTTATTTTGCCCAAGGTAGCATGGCTAGTTGA TGCCGGTTGATGGGGCTTAAACCCAGCTCCCTCATCTTCCAGGCCTCTGTACTCCCT ATTCCACTAAACTACCTCTCAGGTTTATTTTTTTAAATTCTTACTCTGCAAGTACAT AGGACCACATTTACCTGGGAAAACAAGAATAAAGGCTGCTCTGCATTTTTTAGAAAC TTTTTTGAAAGGGAGATGGGAATGCCTGCACCCCCAAGTCCAGACCAACACAATGGT TAATTGAGATGAATAATAAAGGAAAGACTGTTCTGGGCTTCCCAGAATAGCTTGGTC CTTAAATTGTGGCACAAACAACCTCCTGTCAGAGCCAGCCTCCTGCCAGGAAGAGGG GTAGGAGACTAGAGGCCGTGTGTGCAGCCTTGCCCTGAAGGCTAGGGTGACAATTTG GAGGCTGTCCAAACACCCTGGCCTCTAGAGCTGGCCTGTCTATTTGAAATGCCGGCT CTGATGCTAATCGGCGACCCTCAGGCAAGTTACTTAACCTTACATGCCTCAGTTTTC TCATCTGGAAAATGAGAACCCTAGGTTTAGGGTTGTTAGAAAAGTTAAATGAGTTAA GACAAGTGCCTGGGACACAGTAGCCTCTTGTGTGTGTTTATCATTATGTCCTCAGCA GGTCGTAGAAGCAGCTTCTCAGGTGTGAGGCTGGCGCGATTATCTGGAGTGGGTTGG GTTTTCTAGGATGGACCCCCTGCTGCATTTTCCTCATTCATCCACCAGGGCTTAATG GGGAATCAAGGAATCCATGTGTAACTGTATAATAACTGTAGCCACACTCCAATGACC ACCTACTAGTTGTCCCTGGCACTGCTTATACATATGTCCATCAAATCAATCCTATGA AGTAGATACTGTCTTCATTTTATAGATCAGAGACAATTGGGGTTCAGAGAGCTGATG TGATTTTCCCAGGGTCACAGAGAGTCCCAGATTCAGGCACAACTCTTGTATTCCAAG ACACAACCACTACATGTCCAAAGGCTGCCCAGAGCCACCGGGCACGGCAAATTGTGA CATATCCCTAAAGAGGCTGAGCACCTGGTCAGGATCTGATGGCTGACAGTGTGTCCA GATGCAGAGCTGGAGTGGGGGAGGGGAAGGGGGGCTCCTTGGGACAGAGAAGGCTTT CTGTGCTTTCTCTGAAGGGAGCAGTCTGAGGACCAAGGGAACCCGGCAAACAGCACC TCAGGTACTCCAGGCCCTCCTGGCTGGAGAGGGCTGTGGCAATGGAAAATTAGTGCC AACTGCAATGAGTCAGCCTCGGTTAAATAGAGAGTGAAGAATGCTGGACAGGAACCT CCACCCTCATGTCACATTTCTTCAGTGTGACCCTTCTGGCCCCTCTCCTCCTGACAG CGGAACAATGACTGCCCCGATAGGTGAGGCTGGAGGAAGAATCAGTCCTGTCCTTGG CAAGCTCTTCACTATGACAGTAAAGGCTCTCTGCCTGCTGCCAAGGCCTGTGACTTT CTAACCTGGCCTCACGCTGGGTAAGCTTAAGGTAGAGGTGCAGGATTAGCAAGCCCA CCTGGCTACCAGGCCGACAGCTACATCTTTCAACTGACCCTGATCAACGAAGAGGGA CTTGTGTCTCTCAGTTGGTTCCAAATGAAACCAGGGAGCAGGGGCGTTAGGAAGCTC CAACAGGATGGTACTTAATGGGGCATTTGAGTGGAGAGGTAGGTGACATAGTGCTTT GGAGCCCAGGGAGGGAAAGGTTCTGCTGAAGTTGAATTCAAGACTGTTCTTTCATCA CAAACTTGAGTTTCCTGGACATTTGTTTGCAGAAACAACCGTAGGGTTTTGCCTTAA CCTCGTGGGTTTATTATTACCTCATAGGGACTTTGCCTCCTGACAGCAGTTTATGGG TGTTCATTGTGGCACTTGAGTTTTCTTGCATACTTGTTAGAGAAACCAAGTTTGTCA TCAACTTCTTATTTAACCCCCTGGCTATAACTTCATGGATTATGTTATAATTAAGCC ATCCAGAGTAAAATCTGTTTAGATTATCTTGGAGTAAGGGGGAAAAAATCTGTAATT TTTTCTCCTCAACTAGATATATACATAAAAAATGATTGTATTGCTTCATTTAAAAAA TATAACGCAAAATCTCTTTTCCTTCTAAAAAAAAAAAAAAAAAA(SEQIDNO: 197) >NP_976075.1CD59glycoproteinpreproprotein[Homosapiens] MGIQGGSVLFGLLLVLAVFCHSGHSLQCYNCPNPTADCKTAVNCSSDFDACLITKAG LQVYNKCWKFEHCNENDVTTRLRENELTYYCCKKDLCNFNEQLENGGTSLSEKTVLL LVTPFLAAAWSLHP(SEQIDNO:198) HumanC1C2from NM_005928.4Homosapiensmilkfatglobule-EGFfactor8 MFGE8 protein(MFGE8),transcriptvariant1,mRNA AGAACCCCGCGGGGTCTGAGCAGCCCAGCGTGCCCATTCCAGCGCCCGCGTCCCCGC AGCATGCCGCGCCCCCGCCTGCTGGCCGCGCTGTGCGGCGCGCTGCTCTGCGCCCCC AGCCTCCTCGTCGCCCTGGATATCTGTTCCAAAAACCCCTGCCACAACGGTGGTTTA TGCGAGGAGATTTCCCAAGAAGTGCGAGGAGATGTCTTCCCCTCGTACACCTGCACG TGCCTTAAGGGCTACGCGGGCAACCACTGTGAGACGAAATGTGTCGAGCCACTGGGC CTGGAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCGTCTGTGCGTGTGACC TTCTTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATG GTCAATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTG CTGCGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGT CATGAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGAT TTCATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAAC GCGGTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTAC CCCACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTG AACGGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATC ACGGCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCC TATGCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGT AACGATCAGTGGCTGCAGGTGGACCTGGGCTCCTCGAAGGAGGTGACAGGCATCATC ACCCAGGGGGCCCGTAACTTTGGCTCTGTCCAGTTTGTGGCATCCTACAAGGTTGCC TACAGTAATGACAGTGCGAACTGGACTGAGTACCAGGACCCCAGGACTGGCAGCAGT AAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTGTTTGAGACG CCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAACCGCATCGCC CTGCGCCTGGAGCTGCTGGGCTGTTAGTGGCCACCTGCCACCCCCAGGTCTTCCTGC TTTCCATGGGCCCGCTGCCTCTTGGCTTCTCAGCCCCTTTAAATCACCATAGGGCTG GGGACTGGGGAAGGGGAGGGTGTTCAGAGGCAGCACCACCACACAGTCACCCCTCCC TCCCTCTTTCCCACCCTCCACCTCTCACGGGCCCTGCCCCAGCCCCTAAGCCCCGTC CCCTAACCCCCAGTCCTCACTGTCCTGTTTTCTTAGGCACTGAGGGATCTGAGTAGG TCTGGGATGGACAGGAAAGGGCAAAGTAGGGCGTGTGGTTTCCCTGCCCCTGTCCGG ACCGCCGATCCCAGGTGCGTGTGTCTCTGTCTCTCCTAGCCCCTCTCTCACACATCA CATTCCCATGGTGGCCTCAAGAAAGGCCCGGAAGCGCCAGGCTGGAGATAACAGCCT CTTGCCCGTCGGCCCTGCGTCGGCCCTGGGGTACCATGTGGCCACAACTGCTGTGGC CCCCTGTCCCCAAGACACTTCCCCTTGTCTCCCTGGTTGCCTCTCTTGCCCCTTGTC CTGAAGCCCAGCGACACAGAAGGGGGTGGGGGGGGTCTATGGGGAGAAAGGGAGCGA GGTCAGAGGAGGGCATGGGTTGGCAGGGTGGGCGTTTGGGGCCCTCTATGCTGGCTT TTCACCCCAGAGGACACAGGCAGCTTCCAAAATATATTTATCTTCTTCACGGGAA (SEQIDNO:199) >NP_005919.2lactadherinisoformapreproprotein[Homo sapiens] MPRPRLLAALCGALLCAPSLLVALDICSKNPCHNGGLCEEISQEVRGDVFPSYTCTC LKGYAGNHCETKCVEPLGLENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMV NAWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDF IHDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELN GCANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGN DQWLQVDLGSSKEVTGIITQGARNFGSVQFVASYKVAYSNDSANWTEYQDPRTGSSK IFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC(SEQIDNO: 200) Human4F2(CD98) >NM_002394.6Homosapienssolutecarrierfamily3member 2(SLC3A2),transcriptvariant3,mRNA GCATTGCGGCTTGGTTTTCTCACCCAGTGCATGTGGCAGGAGCGGTGAGATCACTGC CTCACGGCGATCCTGGACTGACGGTCACGACTGCCTACCCTCTAACCCTGTTCTGAG CTGCCCCTTGCCCACACACCCCAAACCTGTGTGCAGGATCCGCCTCCATGGAGCTAC AGCCTCCTGAAGCCTCGATCGCCGTCGTGTCGATTCCGCGCCAGTTGCCTGGCTCAC ATTCGGAGGCTGGTGTCCAGGGTCTCAGCGCGGGGGACGACTCAGAGTTGGGGTCTC ACTGTGTTGCCCAGACTGGTCTCGAACTCTTGGCCTCAGGTGATCCTCTTCCCTCAG CTTCCCAGAATGCCGAGATGATAGAGACGGGGTCTGACTGTGTTACCCAGGCTGGTC TTCAACTCTTGGCCTCAAGTGATCCTCCTGCCTTAGCTTCCAAGAATGCTGAGGTTA CAGGCACCATGAGCCAGGACACCGAGGTGGATATGAAGGAGGTGGAGCTGAATGAGT TAGAGCCCGAGAAGCAGCCGATGAACGCGGCGTCTGGGGCGGCCATGTCCCTGGCGG GAGCCGAGAAGAATGGTCTGGTGAAGATCAAGGTGGCGGAAGACGAGGCGGAGGCGG CAGCCGCGGCTAAGTTCACGGGCCTGTCCAAGGAGGAGCTGCTGAAGGTGGCAGGCA GCCCCGGCTGGGTACGCACCCGCTGGGCACTGCTGCTGCTCTTCTGGCTCGGCTGGC TCGGCATGCTTGCTGGTGCCGTGGTCATAATCGTGCGAGCGCCGCGTTGTCGCGAGC TACCGGCGCAGAAGTGGTGGCACACGGGCGCCCTCTACCGCATCGGCGACCTTCAGG CCTTCCAGGGCCACGGCGCGGGCAACCTGGCGGGTCTGAAGGGGCGTCTCGATTACC TGAGCTCTCTGAAGGTGAAGGGCCTTGTGCTGGGTCCAATTCACAAGAACCAGAAGG ATGATGTCGCTCAGACTGACTTGCTGCAGATCGACCCCAATTTTGGCTCCAAGGAAG ATTTTGACAGTCTCTTGCAATCGGCTAAAAAAAAGAGCATCCGTGTCATTCTGGACC TTACTCCCAACTACCGGGGTGAGAACTCGTGGTTCTCCACTCAGGTTGACACTGTGG CCACCAAGGTGAAGGATGCTCTGGAGTTTTGGCTGCAAGCTGGCGTGGATGGGTTCC AGGTTCGGGACATAGAGAATCTGAAGGATGCATCCTCATTCTTGGCTGAGTGGCAAA ATATCACCAAGGGCTTCAGTGAAGACAGGCTCTTGATTGCGGGGACTAACTCCTCCG ACCTTCAGCAGATCCTGAGCCTACTCGAATCCAACAAAGACTTGCTGTTGACTAGCT CATACCTGTCTGATTCTGGTTCTACTGGGGAGCATACAAAATCCCTAGTCACACAGT ATTTGAATGCCACTGGCAATCGCTGGTGCAGCTGGAGTTTGTCTCAGGCAAGGCTCC TGACTTCCTTCTTGCCGGCTCAACTTCTCCGACTCTACCAGCTGATGCTCTTCACCC TGCCAGGGACCCCTGTTTTCAGCTACGGGGATGAGATTGGCCTGGATGCAGCTGCCC TTCCTGGACAGCCTATGGAGGCTCCAGTCATGCTGTGGGATGAGTCCAGCTTCCCTG ACATCCCAGGGGCTGTAAGTGCCAACATGACTGTGAAGGGCCAGAGTGAAGACCCTG GCTCCCTCCTTTCCTTGTTCCGGCGGCTGAGTGACCAGCGGAGTAAGGAGCGCTCCC TACTGCATGGGGACTTCCACGCGTTCTCCGCTGGGCCTGGACTCTTCTCCTATATCC GCCACTGGGACCAGAATGAGCGTTTTCTGGTAGTGCTTAACTTTGGGGATGTGGGCC TCTCGGCTGGACTGCAGGCCTCCGACCTGCCTGCCAGCGCCAGCCTGCCAGCCAAGG CTGACCTCCTGCTCAGCACCCAGCCAGGCCGTGAGGAGGGCTCCCCTCTTGAGCTGG AACGCCTGAAACTGGAGCCTCACGAAGGGCTGCTGCTCCGCTTCCCCTACGCGGCCT GACTTCAGCCTGACATGGACCCACTACCCTTCTCCTTTCCTTCCCAGGCCCTTTGGC TTCTGATTTTTCTCTTTTTTAAAAACAAACAAACAAACTGTTGCAGATTATGAGTGA ACCCCCAAATAGGGTGTTTTCTGCCTTCAAATAAAAGTCACCCCTGCATGGTGAA (SEQIDNO:201) >NP_002385.34F2cell-surfaceantigenheavychainisoform c[Homosapiens] MELQPPEASIAVVSIPRQLPGSHSEAGVQGLSAGDDSELGSHCVAQTGLELLASGDP LPSASQNAEMIETGSDCVTQAGLQLLASSDPPALASKNAEVTGTMSQDTEVDMKEVE LNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAAAKFTGLSKEELLK VAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVRAPRCRELPAQKWWHTGALYRIG DLQAFQGHGAGNLAGLKGRLDYLSSLKVKGLVLGPIHKNQKDDVAQTDLLQIDPNFG SKEDFDSLLQSAKKKSIRVILDLTPNYRGENSWESTQVDTVATKVKDALEFWLQAGV DGFQVRDIENLKDASSFLAEWQNITKGFSEDRLLIAGTNSSDLQQILSLLESNKDLL LTSSYLSDSGSTGEHTKSLVTQYLNATGNRWCSWSLSQARLLTSFLPAQLLRLYQLM LFTLPGTPVFSYGDEIGLDAAALPGQPMEAPVMLWDESSFPDIPGAVSANMTVKGQS EDPGSLLSLFRRLSDQRSKERSLLHGDFHAFSAGPGLFSYIRHWDQNERFLVVLNFG DVGLSAGLQASDLPASASLPAKADLLLSTPGREEGSPLELERLKLEPHEGLLLREP YAA(SEQIDNO:202) HumanTFR2 >NM_003227.4Homosapienstransferrinreceptor2(TFR2), transcriptvariant1,mRNA ATCGCTGGGGGACAGCCTGCAGGCTTCAGGAGGGGACACAAGCATGGAGCGGCTTTG GGGTCTATTCCAGAGAGCGCAACAACTGTCCCCAAGATCCTCTCAGACCGTCTACCA GCGTGTGGAAGGCCCCCGGAAAGGGCACCTGGAGGAGGAAGAGGAAGACGGGGAGGA GGGGGCGGAGACATTGGCCCACTTCTGCCCCATGGAGCTGAGGGGCCCTGAGCCCCT GGGCTCTAGACCCAGGCAGCCAAACCTCATTCCCTGGGCGGCAGCAGGACGGAGGGC TGCCCCCTACCTGGTCCTGACGGCCCTGCTGATCTTCACTGGGGCCTTCCTACTGGG CTACGTCGCCTTCCGAGGGTCCTGCCAGGCGTGCGGAGACTCTGTGTTGGTGGTCAG TGAGGATGTCAACTATGAGCCTGACCTGGATTTCCACCAGGGCAGACTCTACTGGAG CGACCTCCAGGCCATGTTCCTGCAGTTCCTGGGGGAGGGGCGCCTGGAGGACACCAT CAGGCAAACCAGCCTTCGGGAACGGGTGGCAGGCTCGGCCGGGATGGCCGCTCTGAC TCAGGACATTCGCGCGGCGCTCTCCCGCCAGAAGCTGGACCACGTGTGGACCGACAC GCACTACGTGGGGCTGCAATTCCCGGATCCGGCTCACCCCAACACCCTGCACTGGGT CGATGAGGCCGGGAAGGTCGGAGAGCAGCTGCCGCTGGAGGACCCTGACGTCTACTG CCCCTACAGCGCCATCGGCAACGTCACGGGAGAGCTGGTGTACGCCCACTACGGGCG GCCCGAAGACCTGCAGGACCTGCGGGCCAGGGGCGTGGATCCAGTGGGCCGCCTGCT GCTGGTGCGCGTGGGGGTGATCAGCTTCGCCCAGAAGGTGACCAATGCTCAGGACTT CGGGGCTCAAGGAGTGCTCATATACCCAGAGCCAGCGGACTTCTCCCAGGACCCACC CAAGCCAAGCCTGTCCAGCCAGCAGGCAGTGTATGGACATGTGCACCTGGGAACTGG AGACCCCTACACACCTGGCTTCCCTTCCTTCAATCAAACCCAGTTCCCTCCAGTTGC ATCATCAGGCCTTCCCAGCATCCCAGCCCAGCCCATCAGTGCAGACATTGCCTCCCG CCTGCTGAGGAAGCTCAAAGGCCCTGTGGCCCCCCAAGAATGGCAGGGGAGCCTCCT AGGCTCCCCTTATCACCTGGGCCCCGGGCCACGACTGCGGCTAGTGGTCAACAATCA CAGGACCTCCACCCCCATCAACAACATCTTCGGCTGCATCGAAGGCCGCTCAGAGCC AGATCACTACGTTGTCATCGGGGCCCAGAGGGATGCATGGGGCCCAGGAGCAGCTAA ATCCGCTGTGGGGACGGCTATACTCCTGGAGCTGGTGCGGACCTTTTCCTCCATGGT GAGCAACGGCTTCCGGCCCCGCAGAAGTCTCCTCTTCATCAGCTGGGACGGTGGTGA CTTTGGAAGCGTGGGCTCCACGGAGTGGCTAGAGGGCTACCTCAGCGTGCTGCACCT CAAAGCCGTAGTGTACGTGAGCCTGGACAACGCAGTGCTGGGGGATGACAAGTTTCA TGCCAAGACCAGCCCCCTTCTGACAAGTCTCATTGAGAGTGTCCTGAAGCAGGTGGA TTCTCCCAACCACAGTGGGCAGACTCTCTATGAACAGGTGGTGTTCACCAATCCCAG CTGGGATGCTGAGGTGATCCGGCCCCTACCCATGGACAGCAGTGCCTATTCCTTCAC GGCCTTTGTGGGAGTCCCTGCCGTCGAGTTCTCCTTTATGGAGGACGACCAGGCCTA CCCATTCCTGCACACAAAGGAGGACACTTATGAGAACCTGCATAAGGTGCTGCAAGG CCGCCTGCCCGCCGTGGCCCAGGCCGTGGCCCAGCTCGCAGGGCAGCTCCTCATCCG GCTCAGCCACGATCGCCTGCTGCCCCTCGACTTCGGCCGCTACGGGGACGTCGTCCT CAGGCACATCGGGAACCTCAACGAGTTCTCTGGGGACCTCAAGGCCCGCGGGCTGAC CCTGCAGTGGGTGTACTCGGCGCGGGGGGACTACATCCGGGCGGCGGAAAAGCTGCG GCAGGAGATCTACAGCTCGGAGGAGAGAGACGAGCGACTGACACGCATGTACAACGT GCGCATAATGCGGGTGGAGTTCTACTTCCTTTCCCAGTACGTGTCGCCAGCCGACTC CCCGTTCCGCCACATCTTCATGGGCCGTGGAGACCACACGCTGGGCGCCCTGCTGGA CCACCTGCGGCTGCTGCGCTCCAACAGCTCCGGGACCCCCGGGGCCACCTCCTCCAC TGGCTTCCAGGAGAGCCGTTTCCGGCGTCAGCTAGCCCTGCTCACCTGGACGCTGCA AGGGGCAGCCAATGCGCTTAGCGGGGATGTCTGGAACATTGATAACAACTTCTGAGG CCCTGGGGATCCTCACATCCCCGTCCCCCAGTCAAGAGCTCCTCTGCTCCTCGCTTG AATGATTCAGGGTCAGGGAGGTGGCTCAGAGTCCACCTCTCATTGCTGATCAATTTC TCATTACCCCTACACATCTCTCCACGGAGCCCAGACCCCAGCACAGATATCCACACA CCCCAGCCCTGCAGTGTAGCTGACCCTAATGTGACGGTCATACTGTCGGTTAATCAG AGAGTAGCATCCCTTCAATCACAGCCCCTTCCCCTTTCTGGGGTCCTCCATACCTAG AGACCACTCTGGGAGGTTTGCTAGGCCCTGGGACCTGGCCAGCTCTGTTAGTGGGAG AGATCGCTGGCACCATAGCCTTATGGCCAACAGGTGGTCTGTGGTGAAAGGGGCGTG GAGTTTCAATATCAATAAACCACCTGATATCAATAA(SEQIDNO:203) >NP_003218.2transferrinreceptorprotein2isoform1 [Homosapiens] MERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELR GPEPLGSRPRQPNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGSCQACGDS VLVVSEDVNYEPDLDFHQGRLYWSDLQAMFLQFLGEGRLEDTIRQTSLRERVAGSAG MAALTQDIRAALSRQKLDHVWTDTHYVGLQFPDPAHPNTLHWVDEAGKVGEQLPLED PDVYCPYSAIGNVTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVT NAQDFGAQGVLIYPEPADESQDPPKPSLSSQQAVYGHVHLGTGDPYTPGFPSENQTQ FPPVASSGLPSIPAQPISADIASRLLRKLKGPVAPQEWQGSLLGSPYHLGPGPRLRL VVNNHRTSTPINNIFGCIEGRSEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRT FSSMVSNGFRPRRSLLFISWDGGDFGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLG DDKFHAKTSPLLTSLIESVLKQVDSPNHSGQTLYEQVVFTNPSWDAEVIRPLPMDSS AYSFTAFVGVPAVEFSFMEDDQAYPFLHTKEDTYENLHKVLQGRLPAVAQAVAQLAG QLLIRLSHDRLLPLDFGRYGDVVLRHIGNLNEFSGDLKARGLTLQWVYSARGDYIRA AEKLRQEIYSSEERDERLTRMYNVRIMRVEFYFLSQYVSPADSPFRHIFMGRGDHTL GALLDHLRLLRSNSSGTPGATSSTGFQESRFRRQLALLTWTLQGAANALSGDVWNID NNF (SEQIDNO:204) HumanADAM10 >NM_001110.4HomosapiensADAMmetallopeptidasedomain10 (ADAM10),transcriptvariant1,mRNA GTTGCCGGCCCCTGAAGTGGAGCGAGAGGGAGGTGCTTCGCCGTTTCTCCTGCCAGG GGAGGTCCCGGCTTCCCGTGGAGGCTCCGGACCAAGCCCCTTCAGCTTCTCCCTCCG GATCGATGTGCTGCTGTTAACCCGTGAGGAGGCGGCGGCGGCGGCAGCGGCAGCGGA AGATGGTGTTGCTGAGAGTGTTAATTCTGCTCCTCTCCTGGGCGGCGGGGATGGGAG GTCAGTATGGGAATCCTTTAAATAAATATATCAGACATTATGAAGGATTATCTTACA ATGTGGATTCATTACACCAAAAACACCAGCGTGCCAAAAGAGCAGTCTCACATGAAG ACCAATTTTTACGTCTAGATTTCCATGCCCATGGAAGACATTTCAACCTACGAATGA AGAGGGACACTTCCCTTTTCAGTGATGAATTTAAAGTAGAAACATCAAATAAAGTAC TTGATTATGATACCTCTCATATTTACACTGGACATATTTATGGTGAAGAAGGAAGTT TTAGCCATGGGTCTGTTATTGATGGAAGATTTGAAGGATTCATCCAGACTCGTGGTG GCACATTTTATGTTGAGCCAGCAGAGAGATATATTAAAGACCGAACTCTGCCATTTC ACTCTGTCATTTATCATGAAGATGATATTAACTATCCCCATAAATACGGTCCTCAGG GGGGCTGTGCAGATCATTCAGTATTTGAAAGAATGAGGAAATACCAGATGACTGGTG TAGAGGAAGTAACACAGATACCTCAAGAAGAACATGCTGCTAATGGTCCAGAACTTC TGAGGAAAAAACGTACAACTTCAGCTGAAAAAAATACTTGTCAGCTTTATATTCAGA CTGATCATTTGTTCTTTAAATATTACGGAACACGAGAAGCTGTGATTGCCCAGATAT CCAGTCATGTTAAAGCGATTGATACAATTTACCAGACCACAGACTTCTCCGGAATCC GTAACATCAGTTTCATGGTGAAACGCATAAGAATCAATACAACTGCTGATGAGAAGG ACCCTACAAATCCTTTCCGTTTCCCAAATATTGGTGTGGAGAAGTTTCTGGAATTGA ATTCTGAGCAGAATCATGATGACTACTGTTTGGCCTATGTCTTCACAGACCGAGATT TTGATGATGGCGTACTTGGTCTGGCTTGGGTTGGAGCACCTTCAGGAAGCTCTGGAG GAATATGTGAAAAAAGTAAACTCTATTCAGATGGTAAGAAGAAGTCCTTAAACACTG GAATTATTACTGTTCAGAACTATGGGTCTCATGTACCTCCCAAAGTCTCTCACATTA CTTTTGCTCACGAAGTTGGACATAACTTTGGATCCCCACATGATTCTGGAACAGAGT GCACACCAGGAGAATCTAAGAATTTGGGTCAAAAAGAAAATGGCAATTACATCATGT ATGCAAGAGCAACATCTGGGGACAAACTTAACAACAATAAATTCTCACTCTGTAGTA TTAGAAATATAAGCCAAGTTCTTGAGAAGAAGAGAAACAACTGTTTTGTTGAATCTG GCCAACCTATTTGTGGAAATGGAATGGTAGAACAAGGTGAAGAATGTGATTGTGGCT ATAGTGACCAGTGTAAAGATGAATGCTGCTTCGATGCAAATCAACCAGAGGGAAGAA AATGCAAACTGAAACCTGGGAAACAGTGCAGTCCAAGTCAAGGTCCTTGTTGTACAG CACAGTGTGCATTCAAGTCAAAGTCTGAGAAGTGTCGGGATGATTCAGACTGTGCAA GGGAAGGAATATGTAATGGCTTCACAGCTCTCTGCCCAGCATCTGACCCTAAACCAA ACTTCACAGACTGTAATAGGCATACACAAGTGTGCATTAATGGGCAATGTGCAGGTT CTATCTGTGAGAAATATGGCTTAGAGGAGTGTACGTGTGCCAGTTCTGATGGCAAAG ATGATAAAGAATTATGCCATGTATGCTGTATGAAGAAAATGGACCCATCAACTTGTG CCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGTGGTCGAACCATCACCCTGC AACCTGGATCCCCTTGCAACGATTTTAGAGGTTACTGTGATGTTTTCATGCGGTGCA GATTAGTAGATGCTGATGGTCCTCTAGCTAGGCTTAAAAAAGCAATTTTTAGTCCAG AGCTCTATGAAAACATTGCTGAATGGATTGTGGCTCATTGGTGGGCAGTATTACTTA TGGGAATTGCTCTGATCATGCTAATGGCTGGATTTATTAAGATATGCAGTGTTCATA CTCCAAGTAGTAATCCAAAGTTGCCTCCTCCTAAACCACTTCCAGGCACTTTAAAGA GGAGGAGACCTCCACAGCCCATTCAGCAACCCCAGCGTCAGCGGCCCCGAGAGAGTT ATCAAATGGGACACATGAGACGCTAACTGCAGCTTTTGCCTTGGTTCTTCCTAGTGC CTACAATGGGAAAACTTCACTCCAAAGAGAAACCTATTAAGTCATCATCTCCAAACT AAACCCTCACAAGTAACAGTTGAAGAAAAAATGGCAAGAGATCATATCCTCAGACCA GGTGGAATTACTTAAATTTTAAAGCCTGAAAATTCCAATTTGGGGGTGGGAGGTGGA AAAGGAACCCAATTTTCTTATGAACAGATATTTTTAACTTAATGGCACAAAGTCTTA GAATATTATTATGTGCCCCGTGTTCCCTGTTCTTCGTTGCTGCATTTTCTTCACTTG CAGGCAAACTTGGCTCTCAATAAACTTTTACCACAAATTGAAATAAATATATTTTTT TCAACTGCCAATCAAGGCTAGGAGGCTCGACCACCTCAACATTGGAGACATCACTTG CCAATGTACATACCTTGTTATATGCAGACATGTATTTCTTACGTACACTGTACTTCT GTGTGCAATTGTAAACAGAAATTGCAATATGGATGTTTCTTTGTATTATAAAATTTT TCCGCTCTTAATTAAAAATTACTGTTTAATTGACATACTCAGGATAACAGAGAATGG TGGTATTCAGTGGTCCAGGATTCTGTAATGCTTTACACAGGCAGTTTTGAAATGAAA ATCAATTTACCTTTCTGTTACGATGGAGTTGGTTTTGATACTCATTTTTTCTTTATC ACATGGCTGCTACGGGCACAAGTGACTATACTGAAGAACACAGTTAAGTGTTGTGCA AACTGGACATAGCAGCACATACTACTTCAGAGTTCATGATGTAGATGTCTGGTTTCT GCTTACGTCTTTTAAACTTTCTAATTCAATTCCATTTTTCAATTAATAGGTGAAATT TTATTCATGCTTTGATAGAAATTATGTCAATGAAATGATTCTTTTTATTTGTAGCCT ACTTATTTGTGTTTTTCATATATCTGAAATATGCTAATTATGTTTTCTGTCTGATAT GGAAAAGAAAAGCTGTGTCTTTATCAAAATATTTAAACGGTTTTTTCAGCATATCAT CACTGATCATTGGTAACCACTAAAGATGAGTAATTTGCTTAAGTAGTAGTTAAAATT GTAGATAGGCCTTCTGACATTTTTTTTCCTAAAATTTTTAACAGCATTGAAGGTGAA ACAGCACAATGTCCCATTCCAAATTTATTTTTGAAACAGATGTAAATAATTGGCATT TTAAAGAGAAAGCAAAAACATTTAATGTATTAACAGGCTTATTGCTATGCAGGAAAT AGAAGGGGCATTACAAAAATTGAAGCTTGTGACATATTTATTGCTTCTGTTTTCCAA CTACATCACTTCAACTAGAAGTAAAGCTATGATTTTCCTGACTTCACATAGGAGGCA AATTTAGAGAAAGTTGTAAAGATTTCTATGTTTTGGGTTTTTTTTTTTCCTTTTTTT TTTTAAGAGTATAAGGTTTACACAATCATTCTCATAATGTGACGCAAGCCAGCAAGG CCAAAAATGCTAGAGAAAATAACGGGATCTCTTCCTTGTAAACTTGTACAGTATGTG GTGACTTTTTCAAAATACAGCTTTTTGTACATGATTTAGAGACAAATTTTGTACATG AAACCCCAGATAGACTATAAATAATTCTAAACAAACAAGTAGGTAGATATGTATGTA ATTGCTTTTAAATCATTTAAATGCCTTTGTTTTTGGACTGTGCAAAGGTTGGAAGTG GGTTTGCATTTCTAAAATGGTGACTTTTATTCTGCAAGAGTTCTTAGTAACTTCTTG AGTGTGGTAGACTTTGGAACATGTAAATTTTTTGCTTGTAATGTTATCCTGTGGTAG GATTTTGGCAGGTACACACACTGCCCTATTTTATTTTGAGTCTAAGTTAAATGTTTT CTGAAAAGAGATACATGCACTGAACTCTTTCCACTGCGAATCAAGATGTGGTAATAT AAAAGGATCAAGACAAATGAGATCTAATACTACTGTCAGTTTTAATGTCCACTGTGT TTTATACAGTATCTTTTTTTGTTCACTTTGGAAATTTTTACTAAAAATTGCAAAAAA TAAAGTATTGTGCAAAGATGTAAGGTTTTTTGAAACTTGAAATGCATTAATAAATAG ACGATTAAATCAACTTGAAGGTTCTATACTCTTTGAACTCTGAGAACTATCACAAGA AGCTTCCCACAAGGCAGTGTTTTCTTACAGTTGTCTCTTCCTACAAAAGTATAGATT ATCTTTATTCTTAATACTTTGGAATCCATGTAGAAAATTTCCAGTTAGATACTCTGC GTACACACAATAAACCTTTTTAAAACACCCAACTAATCTCAACTGCATTACATTGTT TCTAATCAATATTCAGTGCTTGTCTTGGTGGAAGAGGTGAGTCATTTTGAAAACTTA TGGTCTTGTTTTTATGTGTTTTTCAAAGTTTTGAATGCTAAGTACCTCATTTATTTT AAAAAGCCTAGTTTAATGATAAGTTTGTTTAAAATTTTGAGCCATCATTTTTCTCTT CATAGCAAATAAGGAGAGAATTGACATTTCAGTGTTACCTAGAAAAGGAATTGTAAG CCCAGAATAATTCCCTGCATGAGGTAATCTGCTTCAAATTCTTTTTTTAGTCAAGGT TAGCTATAAGTAATACTTGTTAAATGAGTAAATATGTAATACTTTGTGAATTACTTT GTTAATTTAGGAGCATCAAATGTATATTATGTTTAGTTATTTATGAAACTCTCAATA TTGATTGATTTGGGTAATTATAAATTAGTTATTTTTACTTGTAATTGAATGCTTAAA TTCTGTTTACAGTCCGTCCTCTCTCCCTCCATCCCTCCCTCCCCAGTTTTATAAATT CAGGTACCAATTCACAAACAAAATCAGAAATAAAATAAATTTATTGACTGCTTCTGG ATTTAGCATTCCCTGTAGTGTCAAGCAATGTCATGCAGTTTGGGGAAGCATTTATTT AAGGAAATGACAACTTTCTCTGATCAGTCTTGTTTTGTGAGGTGTCTTCAACACTTT ATGCTTTGGGTACTTCGTGTTTGTCACAGTCTTAGGATAGTGAAATCTGATTTGTCC AAGCGGAGCAAACTACTCGACCCTCAGTCCTTGTATTTGTCCCTGTAGTAAGACCTA ATTATTATTATTTCTTAAAGATGGGATTGGTGTCCTTGGCAACTATGAAATTTCGGG GCTTGTGCATGAGAAGGCATTTCTTATTAAGTATTTCTAATTGAAGGTATCAGAGTG TCAAGCATTACAAACCTGGACAGTTCACCTGGAGGAGTACAAGAAGAGATATTCATT ATCCATATTTAAAGGGTCAAGGTTTCCCAAAACCAGGGTGCAAGCCAGATGTAGTTT TAAAGCAGCTGCCAGGGACAGTTCATCTTTAGAGAAGTCACTAAAGTTGTAAGAAAT TTTAGTTTCCCCAAAACCACTTTCAACTTCTTAGAAACTAGAAAGACAATTGGTTTG CCCCACAGAGGACAACTTCAGTTTCAGCATCTCTCATGTTGTGTTCTTGATTAAAAA CAACTTCCATTTGATATACTTTTCCGTTTATTACCAGTTTAGTTTTTTCACTATTGT TTCTGTATTCAACTCTTTATATGATTAGGATAGAAATTTAGCCCTTCTGTTTTATAT TACTATATTGTTTGTGTGTCTTAGATATATACATGTATGTACTATTTTCAGTAGAAA TTCATGTATTTTATAATTGGTAAGTTCTTCAGAGCATCTCTTCTATAAAAAGCAACA GGATGCTAGGTAAAACGGAGCATTGAGCAAAATACTGATTAGTTTTTGCTTTTTCCT GAAATCTACACTAAAGTGATAGGGTGTGGGGTAATCCAACAAGGACAAGGTGAATTG AACAAGAACGAAATCTGGAAGCAGATGAAGGAGTACTATTGATTGGGCAGACCCAGG GAAGTCAAATCCTAAACCAGCAGTGGGAACACAACAGAATGGTGTAGTTTGCACTGG TAAGATTTGGGTACCTGGCAGGGCTGGGTGCGGTGGCTCACACCTGTAATCCCAGCA CTTTGGGAGGCCAAGGCGGGTGGATCACTTGAGGTCAGGAGTTCGAGACCACCCTGG CCAACATGGTGAAACCCCGTCTCTACTAAAAATACAGCTGGGCGTGGTGGCACATGC TTGTAATCCCAGCTACTCGGGAGGCAGAGGCAGGAGATTTGCTTGAACCCGGGAGGC AGAGGCAGGAGATTTGCTTGAACCCAGGAGGCAGAGGCTGCAGTGAGCCGCGATTGC GCCATTGCACTCCAGCCTGGGTGACAGAGCGAGACTCTGTCTCAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAATTTGAGTACCTGGCCTTTGTTAC TTTTTTTCTATGTGTGTGACAAAAACATAATATGCACACTTTTGTAACCCACCTTTC TCATTTAATGGTACATTGATAATGTATATCACATTAACTACTCTAAATATTTCTGTG GATGTATGTTTTTTTTTTTCTTAACCAATTTCCCATTGTTTGGACATGTAGGTTCCA CATTGTTTATTATTTTAAACAATTCTAAAGAATTTTAAACAATTCTTAGGAAAATCC TCAGCCTAATAATGAAATTAATTCCTAAAAGTGGAATTGTTGGGGTAAAGGTTTTTT GAGGGACATTGATAAAAATTATGGTACTGTCTCCCAGATAGATGTACCAAGTTATAC TACCACGATTTAATATATATATATATATATATTAAATCAGAGTCCCATCCTTAGAAA TCCACATATATGCAGCCACATGAATGTATTAGAAACAATAATAGAAGACTCATGCTT AATTCAGTTGATTAGCTTTAGACATAATTCAAATGCAAGTCAAATTGAGTGCCCTAA TTGTGGTCTCTTAAGTACCATTTTTCTTCAAGGGAACCAGACTCCTTTGGATAAATC ACTAATTCCACCTGTAAGAAAGAAATGTACAAGAAGAACCTAGGAAACATTGTTTTG TACCAGATCAGAAAGATTCAGGAGGCACCTTAGAAGTTACCACTGGCCAAGGCTGAG ATAACTTTAGCATCAGCAAGGATAATATCTGCAAGAGATTGAAACTCATAGTATTGT ATTTAACTCTGTGAGTTAATGATGGTAGTGGACAGAATTATAGTTACCTTTGGGATA CGCTTTTAAAGAAATTCCAGGTAATAAGAGAAATGATAGAATTAGGATATCACCATT TTACCCCCCCAACAATTTATGGATCTAGACAATAATCGCCAGTGACTGCTAACCTCA CAAAGTGAGAGCAATCAGATTTTGTGCCTCCTAATGGAAGTACATATACCACCTATG AAGCAGTTCTGCCAAAAGTCACATCTCATCATGATGAAGCCTCCTGATCTAACTACC CCTTCATTAGAAATACAGGGGACAGAGGGACAAATAATATACAAGGGACTCAATCAG CAAAATCCAGACTCTGGAAAACTACAAGACATATGGTCCTGCTTCAACAACAGAAAT GCAAAGAGAAAAGACAACGATGGGTTAAAGGAGACTTAAGAGCTACATCTATCAAGA CAATTTATGGACTTATTTGGATACTGATTTGAACAAACTGTTGAGACCATTGGAAAA ATGTGAAAAGTGGATATTTGATATTAAGGTTTTTAATTATTTTTAGGTGTGATAATG GTATTGTTACATTTTTTAAAGGACCCCTTTTAGAGATGCAAATTGAAACACTTAAAA AATGAAATGATACGATGTATAAGTTTTTGCTTAAAAATAAGGATTGAAGTTGGCTGG TGTGTGTGGATATAGTTGAAACAAGATTGGCTGTGAGTTGATAATTATTGAAGCTGG GTGATGGGCACTTGGGGATTTATTATACTATTTTCTCTACCTGTGTTTATATTTGAA ATTTTTCATAGAAGTTTTAAAATGTGGCCAGTTGTGATGGCTCATACCTGTAATCCC AACACTTTGGGAGGCCAAGGTGGGAGGATCACTTGAGCTCAGGAGTTAGAGACCAGC CTGGGCAAAATAGTGAGACTCCATCTCAAAGAAAAAAAAAAAGTGTTTTAAATGTGA ATCAAATTCCTATAGAAGCTGATTCATTACTGTTTTTATTTTAGCAGTAATTCATGA TAATGACCTGTATTCATAATGATTTTCATAATGATTGTTTTAGTGGAATTAAACTTG AACCAGTCAAGCTAACATAATTATATTCTGCTCCAGTTACAATGAATAATTAATTGA TTTCAACTGCTAGGGTGAACTCTTGAAGCTATCAGTCATCCAGCAATCTTAGCAAGC AGGCCATTGGGTCCCTGTTTGCTCTGTCTCTCTCTCTCTCTCTCACTGTTGAAGGGC TTAGCTAACTACTTAAGTAAAATATTTGTTCTCTGTTAAACATGTCAAGGAGTATGG TCAGCTTATCCACATTAAGCCTGTGTGTCCCACGTTGGAGTAAATGTTAAGTAGCTC ACTACAATAAACTAGATTCTTCTGCCCTCTCTTGTTTAAATGATCATGTTCCCTGGA GGTGGAAATAGATCTTTAAAAAGATATTCTGTAGTTGTTTGTTCTCAGTGTAAAAAA ATGAGAATAATTTGATAAGAGTGTAGGTTGTCTTATATAAAAAGTGGTTCCATTTGC ATGAATTTTAGAAAAATCATTTTGGAAAAATGAAGGCTATGTGGTTATACTGAACAC ATTAAGCAATTTTATTCTTTATTTTAAATGAATATTTTATTATCGTTTTCTTCCCTT GCCCTTTGGGTATGGGAGTTAGCCTTTGTGTTTCTAAATACAACAGGCCGGTTTTTA TAAATTAAGGTGTCAATATATTCTTCATTATTTAGTTTTGTGATTGTGGTTAGTTTT CATTTTTCTTAAGTATCTGCTAGTAGCATCTGTAATTAAGTGAAGTGACCTGTTAAC CATTTTCCTCTTTCTCCTCCTTTCCTCCTCCTTGAAACATATCAGAGCATGTTTGAA ATTCTTTGGCTTTTATGGTATGCATTTGCTGATATGCATTGACCAGTTACCTTACTC ACAGATACTTCTTAGGCACTTGATTGTGCCAGGGCCTTGGCTAGATGATAAGAATAC AGTAGTGAACTTAACAGTTTCCCTGCCCTGGTGAAGCGTATGGTCTTGTAGGTGAGA TAGATATCAGATAATCATGTGAATAAATGTACAATTCCAGCTGTGATACATGCTGAG GAGGAGGTTTTTGGTGATCCAAGAGCTGATCATGCAGAGATAGGACTGAGAAAGGAG GGTGGGACGTTGTCACAGCTGATAATGCAGAGATAGGACTGAGAAAGGAGGGTGGGA CATCAGGAAGGTCAGAGAATTCCTTATGAAAGTGATGCTTGAGTCAAAATATGATGG ATGAAGAGAGTTTAAATAGATTACATAGAATTTTTAATAATGTCGATTGGTTATATA CTGGGCACTGATAGCTGATTTTTCTTTGGGGAAAGGTATGTCAGCCTAGTCATTCAG ATTCCTTTATTTTTTTAAATGTTTTTTCATTTTTTGCTTTGCATTGCATTCATTTGC TGAAGAGCTGGCTTGTACTTTGGCAGGTGTCATACTTGGTTATTCTCCTTAGGATAT TGGCCCAACAATCTGGGAGTTGTGAAAGGCGCTTCGCTTTTCAGACCTGGGCGTCTG TATCATGACTATCATAAATTTAGGATTAAGACACCTAGCCTCCTACCAGGATGAATG AGGTGTCCATGTGACCTGCTGTGCCCTGGAATTTTATACATCTTTCTCTCATAGCAC ACACCATATTACAATATAATCCTGCCTCATCTAAGCCAAACTTTCGAGAGAATCATT TACACTCAGTGGCTACTTCAGCTCCCATTCACTTATCAACCTGCTGCAATTTTTCAC AGCCCCCAAAGGACTGCAGTCTGTGCCTTCAGGGAGCTGAGGGTCTAGCGGAAGGAA AGAAACCAGCAGTTACAGTACAGAGGGGTTTGTGTTGGAAACTCTACAAACACAGGA TGCCCTGGTAGCTCAGAGGAAGTGCATATCGAGCATGGTAGGTAGGTAGTGGGAAGA GCCAAGATGACTTCCCAGAGGAGAAAAGCTGGACCTGAGTTTTGGAGTTTCGGTAAA AGTTTGCTCTAACTAGTCCAAGCTGCTGTCACAAGCTTTTAGAAATGATGTAACCAT GGGGCAGTTGACTGTCGTCATGTTCTTTGCTATTTTCATGACTCTGGATGTGCTTTT CCTATTCCCTGGATTGCCCTTTCCCTCGATTCCTCTGCAGGACTGGGCTTTATTAAT CTCCATTTCCTTGAGCTTGGCTATAGTAGGTGTTCAATAAACATTTGTTTTGTTGTG TGCTTTGTAAATAGGCAATGAAGCTGATTTCACAAGATAGGCACAAAAGTTAGTTTC ATTACAACACATTACCAACAGCTGTATTTTTAACTTTTAACATATCTCATTCTAAAT CCTGTGGCAGCACAACCTCCTTCCGTCATACCTGGAGATAAATTTTCTTTCAAAATC TAATATGCACTGTATTTATAGAATATGAAACATACCGACCATGTTTTGCAAAAATGG GAAAGGCATAACTTAGCTTTGGGGCATGTAAGTAACAACTCCTGATAGGAGAAGAAA TGTATTCAGAAAGCTCAAATTAGAAATAAAATGGGAGACTCTA(SEQIDNO: 205) >NP_001101.1disintegrinandmetalloproteinasedomain- containingprotein10isoform1preproprotein[Homo sapiens] MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHED QFLRLDFHAHGRHENLRMKRDTSLESDEFKVETSNKVLDYDTSHIYTGHIYGEEGSF SHGSVIDGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQG GCADHSVFERMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQT DHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDESGIRNISEMVKRIRINTTADEKD PTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVETDRDEDDGVLGLAWVGAPSGSSGG ICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTEC TPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKENNCFVESG QPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTA QCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGS ICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQ PGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLM GIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESY QMGHMRR(SEQIDNO:206) Transmembrane >NM_001769.4HomosapiensCD9molecule(CD9),transcript domain2or variant1,mRNA transmembrane AGCCGCCTGCATCTGTATCCAGCGCCAGGTCCCGCCAGTCCCAGCTGCGCGCGCCCC domain3from CCAGTCCCGCACCCGTTCGGCCCAGGCTAAGTTAGCCCTCACCATGCCGGTCAAAGG HumanCD9 AGGCACCAAGTGCATCAAATACCTGCTGTTCGGATTTAACTTCATCTTCTGGCTTGC CGGGATTGCTGTCCTTGCCATTGGACTATGGCTCCGATTCGACTCTCAGACCAAGAG CATCTTCGAGCAAGAAACTAATAATAATAATTCCAGCTTCTACACAGGAGTCTATAT TCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGC TGTGCAGGAGTCCCAGTGCATGCTGGGACTGTTCTTCGGCTTCCTCTTGGTGATATT CGCCATTGAAATAGCTGCGGCCATCTGGGGATATTCCCACAAGGATGAGGTGATTAA GGAAGTCCAGGAGTTTTACAAGGACACCTACAACAAGCTGAAAACCAAGGATGAGCC CCAGCGGGAAACGCTGAAAGCCATCCACTATGCGTTGAACTGCTGTGGTTTGGCTGG GGGCGTGGAACAGTTTATCTCAGACATCTGCCCCAAGAAGGACGTACTCGAAACCTT CACCGTGAAGTCCTGTCCTGATGCCATCAAAGAGGTCTTCGACAATAAATTCCACAT CATCGGCGCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGCATGATCTTCAG TATGATCTTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAGAGTCAGCTTAC ATCCCTGAGCAGGAAAGTTTACCCATGAAGATTGGTGGGATTTTTTGTTTGTTTGTT TTGTTTTGTTTGTTGTTTGTTGTTTGTTTTTTTGCCACTAATTTTAGTATTCATTCT GCATTGCTAGATAAAAGCTGAAGTTACTTTATGTTTGTCTTTTAATGCTTCATTCAA TATTGACATTTGTAGTTGAGCGGGGGGTTTGGTTTGCTTTGGTTTATATTTTTTCAG TTGTTTGTTTTTGCTTGTTATATTAAGCAGAAATCCTGCAATGAAAGGTACTATATT TGCTAGACTCTAGACAAGATATTGTACATAAAAGAATTTTTTTGTCTTTAAATAGAT ACAAATGTCTATCAACTTTAATCAAGTTGTAACTTATATTGAAGACAATTTGATACA TAATAAAAAATTATGACAATGTCCTGGA(SEQIDNO:207) >NP_001760.1CD9antigenisoform1[Homosapiens] MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLREDSQTKSIFEQETNNNNSSFY TGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGELLVIFAIEIAAAIWGYSHK DEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIHYALNCCGLAGGVEQFISDICPKKD VLETFTVKSCPDAIKEVEDNKFHIIGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV (SEQIDNO:208) HumanCD298 >NM_001679.4HomosapiensATPaseNa+/K+transporting subunitbeta3(ATP1B3),mRNA AGTCGGCTCGAGTACTCCCCGTAACGAGGAGGTGTTCTCGGCCGTCCCACCCTTCAC TGCCGTCTCCGGGCTGCGCCGCCGGAGCCGGGACGCGCCTCCGCAGCCCTCGCCGCC TCCATCCCCGCGGCCGCAGCTCCTCTCGCCGTCCGCGCGCACACCATGACGAAGAAC GAGAAGAAGTCCCTCAACCAGAGCCTGGCCGAGTGGAAGCTCTTCATCTACAACCCG ACCACCGGAGAATTCCTGGGGCGCACCGCCAAGAGCTGGGGTTTGATCTTGCTCTTC TACCTAGTTTTTTATGGGTTCCTGGCTGCACTCTTCTCATTCACGATGTGGGTTATG CTTCAGACTCTCAACGATGAGGTTCCAAAATACCGTGACCAGATTCCTAGCCCAGGA CTCATGGTTTTTCCAAAACCAGTGACCGCATTGGAATATACATTCAGTAGGTCTGAT CCAACTTCGTATGCAGGGTACATTGAAGACCTTAAGAAGTTTCTAAAACCATATACT TTAGAAGAACAGAAGAACCTCACAGTCTGTCCTGATGGAGCACTTTTTGAACAGAAG GGTCCAGTTTATGTTGCATGTCAGTTTCCTATTTCATTACTTCAAGCATGCAGTGGT ATGAATGATCCTGATTTTGGCTATTCTCAAGGAAACCCTTGTATTCTTGTGAAAATG AACAGAATAATTGGATTAAAGCCTGAAGGAGTGCCAAGGATAGATTGTGTTTCAAAG AATGAAGATATACCAAATGTAGCAGTTTATCCTCATAATGGAATGATAGACTTAAAA TATTTCCCATATTATGGGAAAAAACTGCATGTTGGGTATCTACAGCCATTGGTTGCT GTTCAGGTCAGCTTTGCTCCTAACAACACTGGGAAAGAAGTAACAGTTGAGTGCAAG ATTGATGGATCAGCCAACCTAAAAAGTCAGGATGATCGTGACAAGTTTTTGGGACGA GTTATGTTCAAAATCACAGCACGTGCATAGTATGAGTAGGATATCTCCACAGAGTAA ATGTTGTGTTGTCTGTCTTCATTTTGTAACAGCTGGACCTTCCATTCTAGAATTATG AGACCACCTTGGAGAAAGGTGTGTGGTACATGACATTGGGTTACATCATAACGTGCT TCCAGATCATAGTGTTCAGTGTCCTCTGAAGTAACTGCCTGTTGCCTCTGCTGCCCT TTGAACCAGTGTACAGTCGCCAGATAGGGACCGGTGAACACCTGATTCCAAACATGT AGGATGGGGGTCTTGTCCTCTTTTTATGTGGTTTAATTGCCAAGTGTCTAAAGCTTA ATATGCCGTGCTATGTAAATATTTTATGGATATAACAACTGTCATATTTTGATGTCA ACAGAGTTTTAGGGATAAAATGGTACCCGGCCAACATCAAGTGACTTTATAGCTGCA AGAAATGTGGTATGTGGAGAAGTTCTGTATGTGAGGAAGGAAAAAAAGAAAATAAAA GTGTGTTTGAAAAATATTATCTTGGGTTCTTTGTAAAATTTATTTTTTACATGCTGA ATTAGCCTCGATCTTTTTGATTAAGAGCACAAACTTTTTTTTGTAAAACATGTAAAA AAAAAAACTGGGATTAATTTTTAGTGTTGGAACTGCCTCTTATTTTAGGCTGTAGAT AAAATAGCATTTTTAGGTTAGCCAGTGTGACTATGCACCTAATTTTTTATGAGATTA AATTCATAAGACTTAATTTGTACAATAGTTTGTGAAATATCTTGTTACTGCTTTTAT TTAGCAGACTGTGGACTGTAATAAAGTATATAAATTGTGAAATATAAAAACTTGGAA CTTATTCAAAGCTTCAAAGCAAA(SEQIDNO:209) >NP_001670.1sodium/potassium-transportingATPasesubunit beta-3[Homosapiens] MTKNEKKSLNQSLAEWKLFIYNPTTGEFLGRTAKSWGLILLFYLVFYGFLAALESFT MWVMLQTLNDEVPKYRDQIPSPGLMVFPKPVTALEYTFSRSDPTSYAGYIEDLKKEL KPYTLEEQKNLTVCPDGALFEQKGPVYVACQFPISLLQACSGMNDPDFGYSQGNPCI LVKMNRIIGLKPEGVPRIDCVSKNEDIPNVAVYPHNGMIDLKYFPYYGKKLHVGYLQ PLVAVQVSFAPNNTGKEVTVECKIDGSANLKSQDDRDKFLGRVMFKITARA(SEQ IDNO:210) Lipidaffinitytag >NM_004985.5HomosapiensKRASproto-oncogene,GTPase modifiedfrom (KRAS),transcriptvariantb,mRNA HumanKRAS CTAGGCGGCGGCCGCGGCGGCGGAGGCAGCAGCGGCGGCGGCAGTGGCGGCGGCGAA GGTGGCGGCGGCTCGGCCAGTACTCCCGGCCCCCGCCATTTCGGACTGGGAGCGAGC GCGGCGCAGGCACTGAAGGCGGCGGCGGGGCCAGAGGCTCAGCGGCTCCCAGGTGCG GGAGAGAGGCCTGCTGAAAATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGG CGTAGGCAAGAGTGCCTTGACGATACAGCTAATTCAGAATCATTTTGTGGACGAATA TGATCCAACAATAGAGGATTCCTACAGGAAGCAAGTAGTAATTGATGGAGAAACCTG TCTCTTGGATATTCTCGACACAGCAGGTCAAGAGGAGTACAGTGCAATGAGGGACCA GTACATGAGGACTGGGGAGGGCTTTCTTTGTGTATTTGCCATAAATAATACTAAATC ATTTGAAGATATTCACCATTATAGAGAACAAATTAAAAGAGTTAAGGACTCTGAAGA TGTACCTATGGTCCTAGTAGGAAATAAATGTGATTTGCCTTCTAGAACAGTAGACAC AAAACAGGCTCAGGACTTAGCAAGAAGTTATGGAATTCCTTTTATTGAAACATCAGC AAAGACAAGACAGGGTGTTGATGATGCCTTCTATACATTAGTTCGAGAAATTCGAAA ACATAAAGAAAAGATGAGCAAAGATGGTAAAAAGAAGAAAAAGAAGTCAAAGACAAA GTGTGTAATTATGTAAATACAATTTGTACTTTTTTCTTAAGGCATACTAGTACAAGT GGTAATTTTTGTACATTACACTAAATTATTAGCATTTGTTTTAGCATTACCTAATTT TTTTCCTGCTCCATGCAGACTGTTAGCTTTTACCTTAAATGCTTATTTTAAAATGAC AGTGGAAGTTTTTTTTTCCTCTAAGTGCCAGTATTCCCAGAGTTTTGGTTTTTGAAC TAGCAATGCCTGTGAAAAAGAAACTGAATACCTAAGATTTCTGTCTTGGGGCTTTTG GTGCATGCAGTTGATTACTTCTTATTTTTCTTACCAATTGTGAATGTTGGTGTGAAA CAAATTAATGAAGCTTTTGAATCATCCCTATTCTGTGTTTTATCTAGTCACATAAAT GGATTAATTACTAATTTCAGTTGAGACCTTCTAATTGGTTTTTACTGAAACATTGAG GGAACACAAATTTATGGGCTTCCTGATGATGATTCTTCTAGGCATCATGTCCTATAG TTTGTCATCCCTGATGAATGTAAAGTTACACTGTTCACAAAGGTTTTGTCTCCTTTC CACTGCTATTAGTCATGGTCACTCTCCCCAAAATATTATATTTTTTCTATAAAAAGA AAAAAATGGAAAAAAATTACAAGGCAATGGAAACTATTATAAGGCCATTTCCTTTTC ACATTAGATAAATTACTATAAAGACTCCTAATAGCTTTTCCTGTTAAGGCAGACCCA GTATGAAATGGGGATTATTATAGCAACCATTTTGGGGCTATATTTACATGCTACTAA ATTTTTATAATAATTGAAAAGATTTTAACAAGTATAAAAAATTCTCATAGGAATTAA ATGTAGTCTCCCTGTGTCAGACTGCTCTTTCATAGTATAACTTTAAATCTTTTCTTC AACTTGAGTCTTTGAAGATAGTTTTAATTCTGCTTGTGACATTAAAAGATTATTTGG GCCAGTTATAGCTTATTAGGTGTTGAAGAGACCAAGGTTGCAAGGCCAGGCCCTGTG TGAACCTTTGAGCTTTCATAGAGAGTTTCACAGCATGGACTGTGTCCCCACGGTCAT CCAGTGTTGTCATGCATTGGTTAGTCAAAATGGGGAGGGACTAGGGCAGTTTGGATA GCTCAACAAGATACAATCTCACTCTGTGGTGGTCCTGCTGACAAATCAAGAGCATTG CTTTTGTTTCTTAAGAAAACAAACTCTTTTTTAAAAATTACTTTTAAATATTAACTC AAAAGTTGAGATTTTGGGGTGGTGGTGTGCCAAGACATTAATTTTTTTTTTAAACAA TGAAGTGAAAAAGTTTTACAATCTCTAGGTTTGGCTAGTTCTCTTAACACTGGTTAA ATTAACATTGCATAAACACTTTTCAAGTCTGATCCATATTTAATAATGCTTTAAAAT AAAAATAAAAACAATCCTTTTGATAAATTTAAAATGTTACTTATTTTAAAATAAATG AAGTGAGATGGCATGGTGAGGTGAAAGTATCACTGGACTAGGAAGAAGGTGACTTAG GTTCTAGATAGGTGTCTTTTAGGACTCTGATTTTGAGGACATCACTTACTATCCATT TCTTCATGTTAAAAGAAGTCATCTCAAACTCTTAGTTTTTTTTTTTTACAACTATGT AATTTATATTCCATTTACATAAGGATACACTTATTTGTCAAGCTCAGCACAATCTGT AAATTTTTAACCTATGTTACACCATCTTCAGTGCCAGTCTTGGGCAAAATTGTGCAA GAGGTGAAGTTTATATTTGAATATCCATTCTCGTTTTAGGACTCTTCTTCCATATTA GTGTCATCTTGCCTCCCTACCTTCCACATGCCCCATGACTTGATGCAGTTTTAATAC TTGTAATTCCCCTAACCATAAGATTTACTGCTGCTGTGGATATCTCCATGAAGTTTT CCCACTGAGTCACATCAGAAATGCCCTACATCTTATTTCCTCAGGGCTCAAGAGAAT CTGACAGATACCATAAAGGGATTTGACCTAATCACTAATTTTCAGGTGGTGGCTGAT GCTTTGAACATCTCTTTGCTGCCCAATCCATTAGCGACAGTAGGATTTTTCAAACCT GGTATGAATAGACAGAACCCTATCCAGTGGAAGGAGAATTTAATAAAGATAGTGCTG AAAGAATTCCTTAGGTAATCTATAACTAGGACTACTCCTGGTAACAGTAATACATTC CATTGTTTTAGTAACCAGAAATCTTCATGCAATGAAAAATACTTTAATTCATGAAGC TTACTTTTTTTTTTTGGTGTCAGAGTCTCGCTCTTGTCACCCAGGCTGGAATGCAGT GGCGCCATCTCAGCTCACTGCAACCTCCATCTCCCAGGTTCAAGCGATTCTCGTGCC TCGGCCTCCTGAGTAGCTGGGATTACAGGCGTGTGCCACTACACTCAACTAATTTTT GTATTTTTAGGAGAGACGGGGTTTCACCCTGTTGGCCAGGCTGGTCTCGAACTCCTG ACCTCAAGTGATTCACCCACCTTGGCCTCATAAACCTGTTTTGCAGAACTCATTTAT TCAGCAAATATTTATTGAGTGCCTACCAGATGCCAGTCACCACACAAGGCACTGGGT ATATGGTATCCCCAAACAAGAGACATAATCCCGGTCCTTAGGTAGTGCTAGTGTGGT CTGTAATATCTTACTAAGGCCTTTGGTATACGACCCAGAGATAACACGATGCGTATT TTAGTTTTGCAAAGAAGGGGTTTGGTCTCTGTGCCAGCTCTATAATTGTTTTGCTAC GATTCCACTGAAACTCTTCGATCAAGCTACTTTATGTAAATCACTTCATTGTTTTAA AGGAATAAACTTGATTATATTGTTTTTTTATTTGGCATAACTGTGATTCTTTTAGGA CAATTACTGTACACATTAAGGTGTATGTCAGATATTCATATTGACCCAAATGTGTAA TATTCCAGTTTTCTCTGCATAAGTAATTAAAATATACTTAAAAATTAATAGTTTTAT CTGGGTACAAATAAACAGGTGCCTGAACTAGTTCACAGACAAGGAAACTTCTATGTA AAAATCACTATGATTTCTGAATTGCTATGTGAAACTACAGATCTTTGGAACACTGTT TAGGTAGGGTGTTAAGACTTACACAGTACCTCGTTTCTACACAGAGAAAGAAATGGC CATACTTCAGGAACTGCAGTGCTTATGAGGGGATATTTAGGCCTCTTGAATTTTTGA TGTAGATGGGCATTTTTTTAAGGTAGTGGTTAATTACCTTTATGTGAACTTTGAATG GTTTAACAAAAGATTTGTTTTTGTAGAGATTTTAAAGGGGGAGAATTCTAGAAATAA ATGTTACCTAATTATTACAGCCTTAAAGACAAAAATCCTTGTTGAAGTTTTTTTAAA AAAAGCTAAATTACATAGACTTAGGCATTAACATGTTTGTGGAAGAATATAGCAGAC GTATATTGTATCATTTGAGTGAATGTTCCCAAGTAGGCATTCTAGGCTCTATTTAAC TGAGTCACACTGCATAGGAATTTAGAACCTAACTTTTATAGGTTATCAAAACTGTTG TCACCATTGCACAATTTTGTCCTAATATATACATAGAAACTTTGTGGGGCATGTTAA GTTACAGTTTGCACAAGTTCATCTCATTTGTATTCCATTGATTTTTTTTTTCTTCTA AACATTTTTTCTTCAAACAGTATATAACTTTTTTTAGGGGATTTTTTTTTAGACAGC AAAAACTATCTGAAGATTTCCATTTGTCAAAAAGTAATGATTTCTTGATAATTGTGT AGTAATGTTTTTTAGAACCCAGCAGTTACCTTAAAGCTGAATTTATATTTAGTAACT TCTGTGTTAATACTGGATAGCATGAATTCTGCATTGAGAAACTGAATAGCTGTCATA AAATGAAACTTTCTTTCTAAAGAAAGATACTCACATGAGTTCTTGAAGAATAGTCAT AACTAGATTAAGATCTGTGTTTTAGTTTAATAGTTTGAAGTGCCTGTTTGGGATAAT GATAGGTAATTTAGATGAATTTAGGGGAAAAAAAAGTTATCTGCAGATATGTTGAGG GCCCATCTCTCCCCCCACACCCCCACAGAGCTAACTGGGTTACAGTGTTTTATCCGA AAGTTTCCAATTCCACTGTCTTGTGTTTTCATGTTGAAAATACTTTTGCATTTTTCC TTTGAGTGCCAATTTCTTACTAGTACTATTTCTTAATGTAACATGTTTACCTGGAAT GTATTTTAACTATTTTTGTATAGTGTAAACTGAAACATGCACATTTTGTACATTGTG CTTTCTTTTGTGGGACATATGCAGTGTGATCCAGTTGTTTTCCATCATTTGGTTGCG CTGACCTAGGAATGTTGGTCATATCAAACATTAAAAATGACCACTCTTTTAATTGAA ATTAACTTTTAAATGTTTATAGGAGTATGTGCTGTGAAGTGATCTAAAATTTGTAAT ATTTTTGTCATGAACTGTACTACTCCTAATTATTGTAATGTAATAAAAATAGTTACA GTGAC(SEQIDNO:211) >NP_004976.2GTPaseKRasisoformb[Homosapiens] MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILD TAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLV GNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEKMS KDGKKKKKKSKTKCVIM(SEQIDNO:212) >Lipidaffinitytagnucleotidesequence AAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATG(SEQIDNO:213) >Lipidaffinitytagpeptidesequence KKKKKKKKTKCVIM(SEQIDNO:214) Myr/Palmtag >NM_002356.7Homosapiensmyristoylatedalaninerich modifiedfrom proteinkinaseCsubstrate(MARCKS),mRNA HumanMARCKS GCACTTGGGCGTTGGACCCCGCATCTTATTAGCAACCAGGGAGATTTCTCCATTTTC CTCTTGTCTACAGTGCGGCTACAAATCTGGGATTTTTTTATTACTTCTTTTTTTTTC GAACTACACTTGGGCTCCTTTTTTTGTGCTCGACTTTTCCACCCTTTTTCCCTCCCT CCTGTGCTGCTGCTTTTTGATCTCTTCGACTAAAATTTTTTTATCCGGAGTGTATTT AATCGGTTCTGTTCTGTCCTCTCCACCACCCCCACCCCCCTCCCTCCGGTGTGTGTG CCGCTGCCGCTGTTGCCGCCGCCGCTGCTGCTGCTGCTCGCCCCGTCGTTACACCAA CCCGAGGCTCTTTGTTTCCCCTCTTGGATCTGTTGAGTTTCTTTGTTGAAGAAGCCA GCATGGGTGCCCAGTTCTCCAAGACCGCAGCGAAGGGAGAAGCCGCCGCGGAGAGGC CTGGGGAGGCGGCTGTGGCCTCGTCGCCTTCCAAAGCGAACGGACAGGAGAATGGCC ACGTGAAGGTAAACGGCGACGCTTCGCCCGCGGCCGCCGAGTCGGGCGCCAAGGAGG AGCTGCAGGCCAACGGCAGCGCCCCGGCCGCCGACAAGGAGGAGCCCGCGGCCGCCG GGAGCGGGGCGGCGTCGCCCTCCGCGGCCGAGAAAGGTGAGCCGGCCGCCGCCGCTG CCCCCGAGGCCGGGGCCAGCCCGGTAGAGAAGGAGGCCCCCGCGGAAGGCGAGGCTG CCGAGCCCGGCTCGCCCACGGCCGCGGAGGGAGAGGCCGCGTCGGCCGCCTCCTCGA CTTCTTCGCCCAAGGCCGAGGACGGGGCCACGCCCTCGCCCAGCAACGAGACCCCGA AAAAAAAAAAGAAGCGCTTTTCCTTCAAGAAGTCTTTCAAGCTGAGCGGCTTCTCCT TCAAGAAGAACAAGAAGGAGGCTGGAGAAGGCGGTGAGGCTGAGGCGCCCGCTGCCG AAGGCGGCAAGGACGAGGCCGCCGGGGGCGCAGCTGCGGCCGCCGCCGAGGCGGGCG CGGCCTCCGGGGAGCAGGCAGCGGCGCCGGGCGAGGAGGCGGCAGCGGGCGAGGAGG GGGCGGCGGGTGGCGACCCGCAGGAGGCCAAGCCCCAGGAGGCCGCTGTCGCGCCAG AGAAGCCGCCCGCCAGCGACGAGACCAAGGCCGCCGAGGAGCCCAGCAAGGTGGAGG AGAAAAAGGCCGAGGAGGCCGGGGCCAGCGCCGCCGCCTGCGAGGCCCCCTCCGCCG CCGGGCCCGGCGCGCCCCCGGAGCAGGAGGCAGCCCCCGCGGAGGAGCCCGCGGCCG CCGCAGCCTCGTCAGCCTGCGCAGCCCCCTCACAGGAGGCCCAGCCCGAGTGCAGTC CAGAAGCCCCCCCAGCGGAGGCGGCAGAGTAAAAGAGCAAGCTTTTGTGAGATAATC GAAGAACTTTTCTCCCCCGTTTGTTTGTTGGAGTGGTGCCAGGTACTGGTTTTGGAG AACTTGTCTACAACCAGGGATTGATTTTAAAGATGTCTTTTTTTATTTTACTTTTTT TTAAGCACCAAATTTTGTTGTTTTTTTTTTTTCTCCCCTCCCCACAGATCCCATCTC AAATCATTCTGTTAACCACCATTCCAACAGGTCGAGGAGAGCTTAAACACCTTCTTC CTCTGCCTTGTTTCTCTTTTATTTTTTATTTTTTCGCATCAGTATTAATGTTTTTGC ATACTTTGCATCTTTATTCAAAAGTGTAAACTTTCTTTGTCAATCTATGGACATGCC CATATATGAAGGAGATGGGTGGGTCAAAAAGGGATATCAAATGAAGTGATGGGGTCA CAATGGGGAAATTGAAGTGGTGCATAACATTGCCAAAATAGTGTGCCACTAGAAATG GTGTAAAGGCTGTCTTTTTTTTTTTTTTAAAAGAAAAGTTATTACCATGTATTTTGT GAGGCAGGTTTACAACACTACAAGTCTTGAGTTAAGAAGGAAAGAGGAAAAAAGAAA AAACACCAATACCCAGATTTAAAAAAAAAAAAACGATCATAGTCTTAGGAGTTCATT TAAACCATAGGAACTTTTCACTTATCTCATGTTAGCTGTACCAGTCAGTGATTAAGT AGAACTACAAGTTGTATAGGCTTTATTGTTTATTGCTGGTTTATGACCTTAATAAAG TGTAATTATGTATTACCAGCAGGGTGTTTTTAACTGTGACTATTGTATAAAAACAAA TCTTGATATCCAGAAGCACATGAAGTTTGCAACTTTCCACCCTGCCCATTTTTGTAA AACTGCAGTCATCTTGGACCTTTTAAAACACAAATTTTAAACTCAACCAAGCTGTGA TAAGTGGAATGGTTACTGTTTATACTGTGGTATGTTTTTGATTACAGCAGATAATGC TTTCTTTTCCAGTCGTCTTTGAGAATAAAGGAAAAAAAATCTTCAGATGCAATGGTT TTGTGTAGCATCTTGTCTATCATGTTTTGTAAATACTGGAGAAGCTTTGACCAATTT GACTTAGAGATGGAATGTAACTTTGCTTACAAAAATTGCTATTAAACTCCTGCTTAA GGTGTTCTAATTTTCTGTGAGCACACTAAAAGCGAAAAATAAATGTGAATAAAATGT ACAAATTTGTTGTGTTTTTTTATGTTCTAATAATACTGAGACTTCTAGGTCTTAGGT TAATTTTTAGGAAGATCTTGCATGCCATCAGGAGTAAATTTTATTGTGGTTCTTAAT CTGAAGTTTTCAAGCTCTGAAATTCATAATCCGCAGTGTCAGATTACGTAGAGGAAG ATCTTACAACATTTCCATGTCAAATCTGTTACCATTTATTGGCATTTAGTTTTCATT TAAGAATTGAACATAATTATTTTTATTGTAGCTATATAGCATGTCAGATTAAATCAT TTACAACAAAAGGGGTGTGAACCTAAGACTATTTAAATGTCTTATGAGAAAATTTCA TAAAGCCATTCTCTTGTCATTCAGGTCCAGAAACAAATTTTAAACTGAGTGAGAGTC TATAGAATCCATACTGCAGATGGGTCATGAAATGTGACCAAATGTGTTTCAAAAATT GATGGTGTATTACCTGCTATTGTAATTGCTTAGTGCTTGGCTAATTTCCAAATTATT GCATAATATGTTCTACCTTAAGAAAACAGGTTTATGTAACAAAGTAATGGTGTTGAA TGGATGATGTCAGTTCATGGGCCTTTAGCATAGTTTTAAGCATCCTTTTTTTTTTTT TTTTTTGAAAGTGTGTTAGCATCTTGTTACTCAAAGGATAAGACAGACAATAATACT TCACTGAATCTTAATAATCTTTACTAGTTTACCTCCTCTGCTCTTTGCCACCCGATA ACTGGATATCTTTTCCTTCAAAGGACCCTAAACTGATTGAAATTTAAGATATGTATC AAAAACATTATTTCATTTAATGCACATCTGTTTTGCTGTTTTTGAGCAGTGTGCAGT TTAGGGTTCATGATAAATCATTGAACCACATGTGTAACAACTGAATGCCAAATCTTA AACTCATTAGAAAAATAACAAATTAGGTTTTGACACGCATTCTTAATTGGAATAATG GATCAAAAATAGTGGTTCATGACCTTACCAAACACCCTTGCTACTAATAAAATCAAA TAACACTTAGAAGGGTATGTATTTTTAGTTAGGGTTTCTTGATCTTGGAGGATGTTT GAAAGTTAAAAATTGAATTTGGTAACCAAAGGACTGATTTATGGGTCTTTCCTATCT TAACCAACGTTTTCTTAGTTACCTAGATGGCCAAGTACAGTGCCTGGTATGTAGTAA GACTCAGTAAAAAAGTGGATTTTTAAAAATAACTCCCAAAGTGAATAGTCAAAAATC CTGTTAGCAAACTGTTATATATTGCTAAGTTTGTTCTTTTAACAGCTGGAATTTATT AAGATGCATTATTTTGATTTTATTCACTGCCTAAAACACTTTGGGTGGTATTGATGG AGTTGGTGGATTTTCCTCCAAGTGATTAAATGAAATTTGACGTATCTTTTCATCCAA AGTTTTGTACATCATGTTTTCTAACGGAAAAAAATGTTAATATGGCTTTTTTGTATT ACTAAAAATAGCTTTGAGATTAAGGAAAAATAAATAACTCTTGTACAGTTCAGTATT GTCTATTAAATCTGTATTGGCAGTATGTATAATGGCATTTGCTGTGGTTACAAAATA CTTCCTCTGGGTTATAATAATCATTTGATCCAATTCCTATTGCTTGTAAAATAAAGT TTTACCAGTTGATATAATCAA(SEQIDNO:215) >NP_002347.5myristoylatedalanine-richC-kinase substrate[Homosapiens] MGAQFSKTAAKGEAAAERPGEAAVASSPSKANGQENGHVKVNGDASPAAAESGAKEE LQANGSAPAADKEEPAAAGSGAASPSAAEKGEPAAAAAPEAGASPVEKEAPAEGEAA EPGSPTAAEGEAASAASSTSSPKAEDGATPSPSNETPKKKKKRFSFKKSFKLSGFSF KKNKKEAGEGGEAEAPAAEGGKDEAAGGAAAAAAEAGAASGEQAAAPGEEAAAGEEG AAGGDPQEAKPQEAAVAPEKPPASDETKAAEEPSKVEEKKAEEAGASAAACEAPSAA GPGAPPEQEAAPAEEPAAAAASSACAAPSQEAQPECSPEAPPAEAAE(SEQID NO:216) >Myr/PalmtagmodifiedfromHumanMARCKS,nucleotide sequence ATGGGTTGCTGTTTCTCCAAGACC(SEQIDNO:217) >Myr/PalmtagmodifiedfromHumanMARCKS,peptide sequence MGCCFSKT(SEQIDNO:218)
[0128] In some embodiments of any of the aspects provided herein, the fusion polypeptide further comprises a peptide linker. The linker may be flexible, rigid, or cleavable. Further, the linker can be linked directly or via another linker (e.g., a peptide of one, two, three, four, five, six, seven, eight, nine, ten or more amino acids) to the fusion polypeptides described herein. Linkers can be configured according to a specific need, e.g., based on at least one of the following characteristics. In some embodiments of any of the aspects, linkers can be configured to have a sufficient length and flexibility such that it can allow for a cleavage at a target site. In some embodiments of any of the aspects, linkers can be configured to allow multimerization of the fusion polypeptides provided herein. In some embodiments of any of the aspects, linkers can be configured to facilitate expression and purification of the fusion proteins or engineered extracellular vesicles provided herein.
[0129] In some embodiments of any of the aspects, a linker can be configured to have any length in a form of a peptide, peptidomimetic, an aptamer, a protein, a nucleic acid (e.g., DNA or RNA), or any combinations thereof. For example, in one embodiment, the linker may be a polypeptide linker such as Gly-Ser-Ser-Gly or a variation thereof as known by one of ordinary skill in the art. In another embodiment the linker may be a protein sequence for a self-cleavable peptide. For example, 2A sequences such as P2A, E2A, F2A, and T2A code for self-cleavable peptides by inducing ribosomal slippage on the mRNA at the 2A site which prevents peptide bond formation. The slippage will result in two separate peptides after translation. This allows the expression of two separate proteins from one promoter region. Any combination of the proteins described herein may be expressed with a self-cleavable peptide as known by one of ordinary skill in the art.
[0130] In some embodiments of any of the aspects, the polypeptide linker is a non-cleavable linker. In some embodiments of any of the aspects, a linker can be a chemical linker of any length.
[0131] In some embodiments of any of the aspects, the linker is an Fc linker. An exemplary nucleic acid sequence encoding an Fc polypeptide is:
TABLE-US-00004 >KY053479.1SyntheticconstructFc-adiponectingene,completecds (SEQIDNO:219) ATGTACAGGATGCAACTCCTGTCTTGCATTGCACTAAGTCTTGCACTTGTCACGAACTCGATATCGGCCA TGGTTAGATCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGT CTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTG GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATG CCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCA CCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAG AAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGG AGATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGA GTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCC TTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCG TGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAGCCAGCGG AAGTGGCGGAGGAGGCGGTCCTGGAGAAGGTGCCTATGTATACCGCTCAGCATTCAGTGTGGGATTGGAG ACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCTTCTACAATCAGCAAAACCACTATG ATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTACTTTGCCTACCACATCACAGTCTA TATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATGCTCTTCACCTATGATCAGTACCAG GAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGGAGGTGGGCGACCAAGTCTGGCTCC AGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGACAATGACTCCACCTTCACAGGCTT TCTTCTCTACCATGACACCAACTCTAGAAAGCTTCCTGGAGAAGGTGCCTATGTATACCGCTCAGCATTC AGTGTGGGATTGGAGACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCTTCTACAATC AGCAAAACCACTATGATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTACTTTGCCTA CCACATCACAGTCTATATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATGCTCTTCACC TATGATCAGTACCAGGAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGGAGGTGGGCG ACCAAGTCTGGCTCCAGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGACAATGACTC CACCTTCACAGGCTTTCTTCTCTACCATGACACCAACACTAGTCCTGGAGAAGGTGCCTATGTATACCGC TCAGCATTCAGTGTGGGATTGGAGACTTACGTTACTATCCCCAACATGCCCATTCGCTTTACCAAGATCT TCTACAATCAGCAAAACCACTATGATGGCTCCACTGGTAAATTCCACTGCAACATTCCTGGGCTGTACTA CTTTGCCTACCACATCACAGTCTATATGAAGGATGTGAAGGTCAGCCTCTTCAAGAAGGACAAGGCTATG CTCTTCACCTATGATCAGTACCAGGAAAATAATGTGGACCAGGCCTCCGGCTCTGTGCTCCTGCATCTGG AGGTGGGCGACCAAGTCTGGCTCCAGGTGTATGGGGAAGGAGAGCGTAATGGACTCTATGCTGATAATGA CAATGACTCCACCTTCACAGGCTTTCTTCTCTACCATGACACCAACTAA.
[0132] The amino acid sequence of the Fc linker is:
TABLE-US-00005 >FcTranslation (SEQIDNO:220) DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHE ALHNHYTQKSLSLSPGK.
[0133] In some embodiments of any of the aspects, the linker is a P2A peptide linker. P2A is a self-cleaving peptide sequence allowing for expression of two proteins from one promoter. In some embodiments, the P2A linker is encoded by the nucleic acid sequence: GCTACTAACTTCAGCCTGCTGAAGCAG (SEQ ID NO: 221). The amino acid sequence of P2A is ATNFSLKQAGDVENPGP (SEQ ID NO: 222).
[0134] In some embodiments of any of the aspects, the linker is provides a multimerization (e.g., dimerization) domain wherein one fusion polypeptide may connect with another fusion polypeptide at each fusion polypeptide's respective multimerization domain. Multimerization of multiple fusion polypeptides will provide multiple fusion polypeptides within close proximity to one another to one or more a target receptor on the target cell, wherein the multiple fusion peptides will enhance receptor clustering on the target cell. Clustering receptors on a target cell will result in enhanced signal transduction. Without receptor clustering a signal may be weaker or not occur all together. For example, Fc domain sequences presented herein dimerize resulting in two fusion polypeptides connected by a covalent bond via the two Fc domains on their respective fusion polypeptide. One preferred embodiment of an Fc domain is from IgG4, herein labeled 4Fc. In other embodiments Fc may be from IgG1, herein labeled Fc. In certain embodiments Fc from other immunoglobulin, (e.g., IgG2, IgG3, etc.) may be used.
[0135] Additional non-limiting examples of linkers that can be used and their properties are further described in detail, e.g., in Chen X, Zaro J L, Shen W C. Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev. 2013; 65(10):1357-1369. doi: 10.1016/j.addr.2012.09.039; O'Shea E K, Lumb K J, Kim P S. Peptide Velcro: design of a heterodimeric coiled coil. Curr Biol. 1993 Oct. 1; 3(10):658-67. doi: 10.1016/0960-9822(93)90063-t. PMID: 15335856; and Miller K M, Arndt K M, Alber T. Protein fusions to coiled-coil domains. Methods Enzymol. 2000; 328:261-82. doi: 10.1016/s0076-6879(00)28402-4. PMID: 11075350, the contents of which are incorporated herein by reference in their entireties.
[0136] The engineered extracellular vesicle compositions provided herein can comprise variations in the configuration of the POI domain, linkers, and/or vesicle targeting domain. The specific combination and localization of these domains can enhance fusion polypeptide anchoring, function, or therapeutic effect, e.g., modulating inflammation.
[0137] Thus, in one aspect, provided herein is an engineered extracellular vesicle comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain, wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle.
[0138] In some embodiments, the POI domain or a fragment thereof is a N-terminal domain of the fusion polypeptide. In some embodiments, the vesicle targeting domain or a fragment thereof is a C-terminal domain of the fusion polypeptide.
[0139] In another aspect, provided herein is an engineered extracellular vesicle comprising: at least one fusion polypeptide comprising: (i) at least one protein of interest (POI) domain or a fragment thereof; and (ii) at least one vesicle targeting domain, wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle, and wherein the vesicle targeting domain is a transmembrane domain relative to a lipid membrane of the extracellular vesicle.
[0140] In some embodiments, the POI domain or a fragment thereof is a C-terminal domain of the fusion polypeptide. In some embodiments, the vesicle targeting domain or a fragment thereof is a N-terminal domain of the fusion polypeptide. In some embodiments, the vesicle targeting domain is in a luminal position relative to the lipid membrane of the extracellular vesicle.
[0141] In some embodiments, the linker is in an exterior position relative to the lipid membrane of the extracellular vesicle. In some embodiments, the linker is a transmembrane linker. In some embodiments, the linker is in a luminal position relative to the lipid membrane of the extracellular vesicle.
[0142] The engineered extracellular vesicle compositions provided herein can comprise one or more of the following fusion polypeptide sequences in Table 4. The vector maps depicting the sequences below are shown in the working examples in
TABLE-US-00006 TABLE4 FullLengthConstructs Fusion NucleicAcidSequence(SEQIDNO:) Polypeptide AminoAcidSequence(SEQIDNO:) hCTLA4-Fc-GPI >Artificialsequence;hCTLA4-Fc-GPI,DNA ATGGCTTGCCTTGGATTTCAGCGGCACAAGGCTCAGCTGAACCTGGCTACCAGGACC TGGCCCTGCACTCTCCTGTTTTTTCTTCTCTTCATCCCTGTCTTCTGCAAAGCAATG CACGTGGCCCAGCCTGCTGTGGTACTGGCCAGCAGCCGAGGCATCGCCAGCTTTGTG TGTGAGTATGCATCTCCAGGCAAAGCCACTGAGGTCCGGGTGACAGTGCTTCGGCAG GCTGACAGCCAGGTGACTGAAGTCTGTGCGGCAACCTACATGATGGGGAATGAGTTG ACCTTCCTAGATGATTCCATCTGCACGGGCACCTCCAGTGGAAATCAAGTGAACCTC ACTATCCAAGGACTGAGGGCCATGGACACGGGACTCTACATCTGCAAGGTGGAGCTC ATGTACCCACCGCCATACTACCTGGGCATAGGCAACGGAACCCAGATTTATGTAATT GATCCAGAACCGTGCCCAGATTCTGACATCGATGACAAAACTCACACATGCCCACCG TGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCC AAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTG AGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCAT AATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGC GTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTC TCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAG CCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAAC CAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAG TGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGAC TCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAG CAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACG CAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACC ACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTG CTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:223) >Artificialsequence;hCTLA4-Fc-GPI,AminoAcid MACLGFQRHKAQLNLATRTWPCTLLFFLLFIPVFCKAMHVAQPAVVLASSRGIASFV CEYASPGKATEVRVTVLRQADSQVTEVCAATYMMGNELTFLDDSICTGTSSGNQVNL TIQGLRAMDTGLYICKVELMYPPPYYLGIGNGTQIYVIDPEPCPDSDIDDKTHTCPP CPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVH NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ PREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLD SDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGT TSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:224) hPDL1-GPI >Artificialsequence;hPDL1-GPI,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGCCAAATAAAGGAAGTGGAACCACTTCA GGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGG ACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:225) >AminoAcidSequence;hPDL1-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:226) hPDL1-C1C2 >ArtificialSequence;hPDL1-C1C2,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGTCGAGCCACTGGGCATGGAG AATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTG GGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAAT GCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGG AGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAG TACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATC CATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTG CATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACG AGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGA TGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCC TCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCA CGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGAT CAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTG TTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAAC CGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG (SEQIDNO:227) >ArtificialSequence,hPDL1-C1C2,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVN AWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFI HDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNG CANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNENAWVAGSYGND QWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQIDNO:228) hPDL1-Fc-GPI >ArtificialSequence;hPDL1-Fc-GPI,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGG CAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTAC ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGA ACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGT TTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:229) >ArtificialSequence;hPDL1-Fc-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLIGTLVTMGLLT (SEQIDNO:230) hPDL2-C1C2 >ArtificialSequence;hPDL2-C1C2,DNA ATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCT TTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTG ACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCC AGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTG GAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGG GACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTAC CTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTT CCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAA GTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTC AGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTT CAAAGTCAGATGGAACCCAGGACCCATCCAACTATCGATGTCGAGCCACTGGGCATG GAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTC TTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTC AATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTG CGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCAT GAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTC ATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCG GTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCC ACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAAC GGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACG GCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTAT GCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAAC GATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAAC TTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCAC AACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG (SEQIDNO:231) >ArtificialSequence;hPDL2-C1C2,AminoAcid MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITA SLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKY LTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPE GLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTIDVEPLGM ENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLL RRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNA VHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQIT ASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKN LFETPILARYVRILPVAWHNRIALRLELLGC (SEQIDNO:232) hPDL2-Fc-GPI >ArtificialSequence;hPDL2-Fc-GPI,DNA ATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCT TTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTG ACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCC AGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTG GAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGG GACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTAC CTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTT CCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAA GTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTC AGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTT CAAAGTCAGATGGAACCCAGGACCCATCCAACTATCGATGACAAAACTCACACATGC CCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCA AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGT GGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACA GGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:233) >ArtificialSequence;hPDL2-Fc-GPI,AminoAcid MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITA SLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKY LTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPE GLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTIDDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVESCSVMHEALHNHYTQKSLSLSPGKIDPNKGS GTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:234) 4F2-h41BBL >ArtificialSequence;4F2-41BBL,DNA ATGAGCCAGGACACCGAGGTGGATATGAAGGAGGTGGAGCTGAATGAGTTAGAGCCC GAGAAGCAGCCGATGAACGCGGCGTCTGGGGCGGCCATGTCCCTGGCGGGAGCCGAG AAGAATGGTCTGGTGAAGATCAAGGTGGCGGAAGACGAGGCGGAGGCGGCAGCCGCG GCTAAGTTCACGGGCCTGTCCAAGGAGGAGCTGCTGAAGGTGGCAGGCAGCCCCGGC TGGGTACGCACCCGCTGGGCACTGCTGCTGCTCTTCTGGCTCGGCTGGCTCGGCATG CTTGCTGGTGCCGTGGTCATAATCGTGGCCTGCCCCTGGGCCGTGTCCGGGGCTCGC GCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCC GACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCC CAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCA GGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTG GCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCC GGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCT GCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCT CGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGC CTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAG GGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCT TCACCGAGGTCGGAATAA (SEQIDNO:235) >ArtificialSequence;4F2-h41BBL,AminoAcid MSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIKVAEDEAEAAAA AKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVIIVACPWAVSGAR ASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLA GVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSA AGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQ GATVLGLFRVTPEIPAGLPSPRSE (SEQIDNO:236) hPDL1-4Fc-GPI >ArtificialSequence;hPDL1-4Fc-GPI,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGGAGTCCAAATATGGTCCCCCATGCCCA TCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTC AGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAG GTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG CAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC ACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAACCAAATAAAGGAAGTGGAACCACT TCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTT GGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:237) >ArtificialSequence;hPDL1-4Fc-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVELFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCK VSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHY TQKSLSLSPGKPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:238) hPDL1-GPI-P2A- >ArtificialSequence;hPDL1-GPI-P2A-hFGL1-GPI,DNA hFGL1-GPI ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGCCAAATAAAGGAAGTGGAACCACTTCA GGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGG ACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTG AAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCTATGGCAAAGGTGTTCAGTTTC ATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAAATTTCGGCGCTCGAGGACTGT GCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGCCTGCTTGAGACCCGGGTCAAA CAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAGAATGAAGTCCAGTTCCTTGAT AAAGGAGATGAGAATACTGTCATTGATCTTGGAAGCAAGAGGCAGTATGCAGATTGT TCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGATTTTACAAAATCAAACCTCTC CAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATGTCCGATGGAGGAGGATGGACT GTAATTCAGAGACGATCTGATGGCAGTGAAAACTTTAACAGAGGATGGAAAGACTAT GAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGTGAATATTGGCTGGGCAATAAA AATCTTCACTTCTTGACCACTCAAGAAGACTACACTTTAAAAATCGACCTTGCAGAT TTTGAAAAAAATAGCCGTTATGCACAATATAAGAATTTCAAAGTTGGAGATGAAAAG AATTTCTACGAGTTGAATATTGGGGAATATTCTGGAACAGCTGGAGATTCCCTTGCG GGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGTCACCAAAGAATGAAATTCAGC ACGTGGGACAGAGATCATGACAACTATGAAGGGAACTGCGCAGAAGAAGATCAGTCT GGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTGAATGGTGTATACTACAGCGGC CCCTACACGGCTAAAACAGACAATGGGATTGTCTGGTACACCTGGCATGGGTGGTGG TATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCAAATGATTTTATTCCAAATGTA ATTCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCAC ACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACT TAG (SEQIDNO:239) >ArtificialSequence;hPDL1-GPI-P2A-hFGL1-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNESLL KQAGDVEENPGPMAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVK QQQVKIKQLLQENEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPL QSPAEFSVYCDMSDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNK NLHFLTTQEDYTLKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLA GNFHPEVQWWASHQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSG PYTAKTDNGIVWYTWHGWWYSLKSVVMKIRPNDFIPNVIPNKGSGTTSGTTRLLSGH TCFTLTGLLGTLVTMGLLT (SEQIDNO:240) Myr-mScarlet >ArtificialSequence;Myr-mScarlet,DNA ATGGGTTGCTGTTTCTCCAAGACCGGCTCGAGCGGCGTGAGCAAGGGCGAGGCAGTG ATCAAGGAGTTCATGCGGTTCAAGGTGCACATGGAGGGCTCCATGAACGGCCACGAG TTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCCTACGAGGGCACCCAGACCGCCAAG CTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTCTCCTGGGACATCCTGTCCCCTCAG TTCATGTACGGCTCCAGGGCCTTCACCAAGCACCCCGCCGACATCCCCGACTACTAT AAGCAGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGC GGCGCCGTGACCGTGACCCAGGACACCTCCCTGGAGGACGGCACCCTGATCTACAAG GTGAAGCTCCGCGGCACCAACTTCCCTCCTGACGGCCCCGTAATGCAGAAGAAGACA ATGGGCTGGGAAGCGTCCACCGAGCGGTTGTACCCCGAGGACGGCGTGCTGAAGGGC GACATTAAGATGGCCCTGCGCCTGAAGGACGGCGGCCGCTACCTGGCGGACTTCAAG ACCACCTACAAGGCCAAGAAGCCCGTGCAGATGCCCGGCGCCTACAACGTCGACCGC AAGTTGGACATCACCTCCCACAACGAGGACTACACCGTGGTGGAACAGTACGAACGC TCCGAGGGCCGCCACTCCACCGGCGGCATGGACGAGCTGTACAAG (SEQIDNO:241) >ArtificialSequence;Myr-mScarlet,AminoAcid MGCCFSKTGSSGVSKGEAVIKEFMRFKVHMEGSMNGHEFEIEGEGEGRPYEGTQTAK LKVTKGGPLPFSWDILSPQFMYGSRAFTKHPADIPDYYKQSFPEGFKWERVMNFEDG GAVTVTQDTSLEDGTLIYKVKLRGTNFPPDGPVMQKKTMGWEASTERLYPEDGVLKG DIKMALRLKDGGRYLADFKTTYKAKKPVQMPGAYNVDRKLDITSHNEDYTVVEQYER SEGRHSTGGMDELYK (SEQIDNO:242) Myr-NanoLuc >ArtificialSequence;Myr-NanoLuc,DNA Luciferase ATGGGTTGCTGTTTCTCCAAGACCGGCTCGAGCGGCGTCTTCACACTCGAAGATTTC GTTGGGGACTGGCGACAGACAGCCGGCTACAACCTGGACCAAGTCCTTGAACAGGGA GGTGTGTCCAGTTTGTTTCAGAATCTCGGGGTGTCCGTAACTCCGATCCAAAGGATT GTCCTGAGCGGTGAAAATGGGCTGAAGATCGACATCCATGTCATCATCCCGTATGAA GGTCTGAGCGGCGACCAAATGGGCCAGATCGAAAAAATTTTTAAGGTGGTGTACCCT GTGGATGATCATCACTTTAAGGTGATCCTGCACTATGGCACACTGGTAATCGACGGG GTTACGCCGAACATGATCGACTATTTCGGACGGCCGTATGAAGGCATCGCCGTGTTC GACGGCAAAAAGATCACTGTAACAGGGACCCTGTGGAACGGCAACAAAATTATCGAC GAGCGCCTGATCAACCCCGACGGCTCCCTGCTGTTCCGAGTAACCATCAACGGAGTG ACCGGCTGGCGGCTGTGCGAACGCATTCTGGCGTAA (SEQIDNO:243) >ArtificialSequence;Myr-NanoLuc,AminoAcid MGCCFSKTGSSGVFTLEDFVGDWRQTAGYNLDQVLEQGGVSSLFQNLGVSVTPIQRI VLSGENGLKIDIHVIIPYEGLSGDQMGQIEKIFKVVYPVDDHHFKVILHYGTLVIDG VTPNMIDYFGRPYEGIAVEDGKKITVTGTLWNGNKIIDERLINPDGSLLERVTINGV TGWRLCERILA (SEQIDNO:244) hSecPDL1-GPI >ArtificialSequence;hSecPDL1-GPI,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGT AATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCCCAAAT AAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTC ACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:245) >ArtificialSequence;hSecPDL1-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPG NILNVSIKICLTLSPSTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:246) Tfr2-h41BBL >ArtificialSequence;Tfr2-h41BBL,DNA ATGGAGCGGCTTTGGGGTCTATTCCAGAGAGCGCAACAACTGTCCCCAAGATCCTCT CAGACCGTCTACCAGCGTGTGGAAGGCCCCCGGAAAGGGCACCTGGAGGAGGAAGAG GAAGACGGGGAGGAGGGGGCGGAGACATTGGCCCACTTCTGCCCCATGGAGCTGAGG GGCCCTGAGCCCCTGGGCTCTAGACCCAGGCAGCCAAACCTCATTCCCTGGGCGGCA GCAGGACGGAGGGCTGCCCCCTACCTGGTCCTGACGGCCCTGCTGATCTTCACTGGG GCCTTCCTACTGGGCTACGTCGCCTTCCGAGGGTCCGCCTGCCCCTGGGCCGTGTCC GGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGTCCCGAG CTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTTGCGCAG CTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCA GGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAG CTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGC GTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAGCCACTG CGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCCGCCTCC TCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTGAGTGCC GGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCAG CTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCC GGACTCCCTTCACCGAGGTCGGAATAA (SEQIDNO:247) >ArtificialSequence;Tfr2-h41BBL,AminoAcid MERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELR GPEPLGSRPRQPNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGSACPWAVS GARASPGSAASPRLRGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPG LAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLR SAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQL TQGATVLGLFRVTPEIPAGLPSPRSE (SEQIDNO:248) CD9tm3-h41BBL >ArtificialSequence;CD9tm3-h41BBL,DNA ATGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCATGCTGGGACTGTTCTTCGGC TTCCTCTTGGTGATATTCGCCATTGAAATAGCTGCGGCCATCTGGGGATATTCCCAC AAGGATGAGGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCG GCCAGCCCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTC TTGGACCTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATC GATGGGCCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGG GGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTAC TATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCC GTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTG GCTTTGACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGT TTCCAGGGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCAC ACTGAGGCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGA CTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA (SEQIDNO:249) >ArtificialSequence;CD9tm3-h41BBL,AminoAcid MGCCGAVQESQCMLGLFFGELLVIFAIEIAAAIWGYSHKDEACPWAVSGARASPGSA ASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTG GLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAAL ALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLG LFRVTPEIPAGLPSPRSE (SEQIDNO:250) Myr/Palm-4F2- >ArtificialSequence;Myr/Palm-4F2-h41BBL,DNA h41BBL ATGGGTTGCTGTTTCTCCAAGACCGGCTCGAGCGGCAGCCAGGACACCGAGGTGGAT ATGAAGGAGGTGGAGCTGAATGAGTTAGAGCCCGAGAAGCAGCCGATGAACGCGGCG TCTGGGGCGGCCATGTCCCTGGCGGGAGCCGAGAAGAATGGTCTGGTGAAGATCAAG GTGGCGGAAGACGAGGCGGAGGCGGCAGCCGCGGCTAAGTTCACGGGCCTGTCCAAG GAGGAGCTGCTGAAGGTGGCAGGCAGCCCCGGCTGGGTACGCACCCGCTGGGCACTG CTGCTGCTCTTCTGGCTCGGCTGGCTCGGCATGCTTGCTGGTGCCGTGGTCATAATC GTGGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGC CCGAGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGAC CTGCGGCAGGGCATGTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGG CCCCTGAGCTGGTACAGTGACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTG AGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTC TTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCA CTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTG ACCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAG GGCCGCTTGCTGCACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAG GCCAGGGCACGCCATGCCTGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTC CGGGTGACCCCCGAAATCCCAGCCGGACTCCCTTCACCGAGGTCGGAATAA (SEQIDNO:251) >ArtificialSequence;Myr/Palm-4F2-h41BBL,AminoAcid MGCCFSKTGSSGSQDTEVDMKEVELNELEPEKQPMNAASGAAMSLAGAEKNGLVKIK VAEDEAEAAAAAKFTGLSKEELLKVAGSPGWVRTRWALLLLFWLGWLGMLAGAVVII VACPWAVSGARASPGSAASPRLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDG PLSWYSDPGLAGVSLTGGLSYKEDTKELVVAKAGVYYVFFQLELRRVVAGEGSGSVS LALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLLHLSAGQRLGVHLHTE ARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE (SEQIDNO:252) Myr/Palm-Link- >ArtificialSequence;Myr/Palm-Link-41BBL,DNA 41BBL(41BBL ATGGGTTGCTGTTTCTCCAAGACCGGCTCGAGCGGCTGGGCCCTGGTCGCGGGGCTG transmembrane CTGCTGCTGCTGCTGCTCGCTGCCGCCTGCGCCGTCTTCCTCGCCTGCCCCTGGGCC domain GTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCGAGACTCCGCGAGGGT included) CCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCATGTTT GCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGT GACCCAGGCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACG AAGGAGCTGGTGGTGGCCAAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTG CGGCGCGTGGTGGCCGGCGAGGGCTCAGGCTCCGTTTCACTTGCGCTGCACCTGCAG CCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGACCGTGGACCTGCCACCC GCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTGCACCTG AGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCC TGGCAGCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATC CCAGCCGGACTCCCTTCACCGAGGTCGGAATAA (SEQIDNO:253) >ArtificialSequence;Myr/Palm-Link-41BBL,AminoAcid MGCCFSKTGSSGWALVAGLLLLLLLAAACAVFLACPWAVSGARASPGSAASPRLREG PELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDT KELVVAKAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPP ASSEARNSAFGFQGRLLHLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEI PAGLPSPRSE (SEQIDNO:254) hPDL1-Link-GPI >ArtificialSequence;hPDL1-Link-GPI,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGGCTCGAGCGGC CCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACG TGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:255) >ArtificialSequence;hPDL1-Link-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELGSSG PNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:256) hSecPDL1- >ArtificialSequence;hSecPDL1-CD9tm2,DNA CD9tm2 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGT AATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCTTCTAC ACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTG GGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCTAG (SEQIDNO:257) >ArtificialSequence;hSecPDL1-CD9tm2,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPG NILNVSIKICLTLSPSTFYTGVYILIGAGALMMLVGFLGCCGAVQESQC (SEQIDNO:258) hSecPDL1- >ArtificialSequence;hSecPDL1-CD9tm2-KRAS,DNA CD9tm2- ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modifiedKRAS ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGT AATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCTTCTAC ACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTG GGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCAAAAAGAAGAAAAAGAAGTCAAAG ACAAAGTGTGTAATTATGTAA (SEQIDNO:259) >ArtificialSequence;hSecPDL1-CD9tm2-KRAS,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPG NILNVSIKICLTLSPSTFYTGVYILIGAGALMMLVGELGCCGAVQESQCKKKKKKSK TKCVIM (SEQIDNO:260) hSecPDL1- >ArtificialSequence;hSecPDL1-CD9tm4,DNA CD9tm4 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGT AATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCATCGGC GCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGCATGATCTTCAGTATGATC TTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAG (SEQIDNO:261) >ArtificialSequence;hSecPDL1-CD9tm4,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPG NILNVSIKICLTLSPSTIGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV (SEQIDNO:262) hSecPDL1-CD81 >ArtificialSequence;hSecPDL1-CD81,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGGT AATATTCTGAATGTGTCCATTAAAATATGTCTAACACTGTCCCCTAGCACCCTGTAC CTCATCGGCATTGCTGCCATCGTGGTCGCTGTGATCATGATCTTCGAGATGATCCTG AGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA (SEQIDNO:263) >ArtificialSequence;hSecPDL1-CD81,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPG NILNVSIKICLTLSPSTLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY (SEQIDNO:264) hCD200-Fc-GPI >ArtificialSequence;hCD200-Fc-GPI,DNA ATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTT TGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGAT GAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAG GAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTC ACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAAC ATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAG GATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGA ACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCT GAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTC TGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAAT GGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGG AAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACC GTCAACAAAGGCATCGATGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAA CTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATG ATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCT GAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAG CCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTG CACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTC CCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAG GTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACCAGGTCAGCCTGACC TGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTC TTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTC TCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCC CTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACC CGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTA ACCATGGGCTTGCTGACTTAG (SEQIDNO:265) >ArtificialSequence;hCD200-Fc-GPI,AminoAcid MERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQ EALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITFWNITLE DEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVF WKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQT VNKGIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDP EVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNG QPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLS LSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:266) hFGL1-GPI >ArtificialSequence;hFGL1-GPI,DNA ATGGCAAAGGTGTTCAGTTTCATCCTTGTTACCACCGCTCTGACAATGGGCAGGGAA ATTTCGGCGCTCGAGGACTGTGCCCAGGAGCAGATGCGGCTCAGAGCCCAGGTGCGC CTGCTTGAGACCCGGGTCAAACAGCAACAGGTCAAGATCAAGCAGCTTTTGCAGGAG AATGAAGTCCAGTTCCTTGATAAAGGAGATGAGAATACTGTCATTGATCTTGGAAGC AAGAGGCAGTATGCAGATTGTTCAGAGATTTTCAATGATGGGTATAAGCTCAGTGGA TTTTACAAAATCAAACCTCTCCAGAGCCCAGCAGAATTTTCTGTTTATTGTGACATG TCCGATGGAGGAGGATGGACTGTAATTCAGAGACGATCTGATGGCAGTGAAAACTTT AACAGAGGATGGAAAGACTATGAAAATGGCTTTGGAAATTTTGTCCAAAAACATGGT GAATATTGGCTGGGCAATAAAAATCTTCACTTCTTGACCACTCAAGAAGACTACACT TTAAAAATCGACCTTGCAGATTTTGAAAAAAATAGCCGTTATGCACAATATAAGAAT TTCAAAGTTGGAGATGAAAAGAATTTCTACGAGTTGAATATTGGGGAATATTCTGGA ACAGCTGGAGATTCCCTTGCGGGGAATTTTCATCCTGAGGTGCAGTGGTGGGCTAGT CACCAAAGAATGAAATTCAGCACGTGGGACAGAGATCATGACAACTATGAAGGGAAC TGCGCAGAAGAAGATCAGTCTGGCTGGTGGTTTAACAGGTGTCACTCTGCAAACCTG AATGGTGTATACTACAGCGGCCCCTACACGGCTAAAACAGACAATGGGATTGTCTGG TACACCTGGCATGGGTGGTGGTATTCTCTGAAATCTGTGGTTATGAAAATTAGGCCA AATGATTTTATTCCAAATGTAATTCCAAATAAAGGAAGTGGAACCACTTCAGGTACT ACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTA GTAACCATGGGCTTGCTGACTTAG (SEQIDNO:267) >ArtificialSequence;hFGL1-GPI,AminoAcid MAKVFSFILVTTALTMGREISALEDCAQEQMRLRAQVRLLETRVKQQQVKIKQLLQE NEVQFLDKGDENTVIDLGSKRQYADCSEIFNDGYKLSGFYKIKPLQSPAEFSVYCDM SDGGGWTVIQRRSDGSENFNRGWKDYENGFGNFVQKHGEYWLGNKNLHFLTTQEDYT LKIDLADFEKNSRYAQYKNFKVGDEKNFYELNIGEYSGTAGDSLAGNFHPEVQWWAS HQRMKFSTWDRDHDNYEGNCAEEDQSGWWFNRCHSANLNGVYYSGPYTAKTDNGIVW YTWHGWWYSLKSVVMKIRPNDFIPNVIPNKGSGTTSGTTRLLSGHTCFTLTGLLGTL VTMGLLT (SEQIDNO:268) hGa19-Fc-GPI >ArtificialSequence;hGal9-Fc-GPI,DNA ATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGG ACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTC AGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGAC ATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACG AGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAG GGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTG AACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACC ATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTCCAGAACCCCCGCACA GTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTCTCCCAGCCTGTCTGTTTCCCA CCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGCGTGTGGCCTGCCAACCCGGCT CCCATTACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCT ACTCCCGCCATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATC ACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTC CTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTC CACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAAC TCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAG AGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGT CAGCACCTGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTG GAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAGACAATCGATGACAAAACTCAC ACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTC CCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTG GTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGC GTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTAC CGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTAC AAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAA GCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAG ATGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGAC ATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCT CCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAG AGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCAC AACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAA GGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACG TTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:269) >ArtificialSequence;hGal9-Fc-GPI,AminoAcid MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGND IAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMV NGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFP PRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFI TTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDN SWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRL EVGGDIQLTHVQTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEY KCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:270) hCD200-GPI >ArtificialSequence;hCD200-GPI,DNA ATGGAGAGGCTGGTGATCAGGATGCCCTTCTCTCATCTGTCTACCTACAGCCTGGTT TGGGTCATGGCAGCAGTGGTGCTGTGCACAGCACAAGTGCAAGTGGTGACCCAGGAT GAAAGAGAGCAGCTGTACACACCTGCTTCCTTAAAATGCTCTCTGCAAAATGCCCAG GAAGCCCTCATTGTGACATGGCAGAAAAAGAAAGCTGTAAGCCCAGAAAACATGGTC ACCTTCAGCGAGAACCATGGGGTGGTGATCCAGCCTGCCTATAAGGACAAGATAAAC ATTACCCAGCTGGGACTCCAAAACTCAACCATCACCTTCTGGAATATCACCCTGGAG GATGAAGGGTGTTACATGTGTCTCTTCAATACCTTTGGTTTTGGGAAGATCTCAGGA ACGGCCTGCCTCACCGTCTATGTACAGCCCATAGTATCCCTTCACTACAAATTCTCT GAAGACCACCTAAATATCACTTGCTCTGCCACTGCCCGCCCAGCCCCCATGGTCTTC TGGAAGGTCCCTCGGTCAGGGATTGAAAATAGTACAGTGACTCTGTCTCACCCAAAT GGGACCACGTCTGTTACCAGCATCCTCCATATCAAAGACCCTAAGAATCAGGTGGGG AAGGAGGTGATCTGCCAGGTGCTGCACCTGGGGACTGTGACCGACTTTAAGCAAACC GTCAACAAAGGCCCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTA TCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGC TTGCTGACTTAG (SEQIDNO:271) >ArtificialSequence;hCD200-GPI,AminoAcid MERLVIRMPFSHLSTYSLVWVMAAVVLCTAQVQVVTQDEREQLYTPASLKCSLQNAQ EALIVTWQKKKAVSPENMVTFSENHGVVIQPAYKDKINITQLGLQNSTITEWNITLE DEGCYMCLFNTFGFGKISGTACLTVYVQPIVSLHYKFSEDHLNITCSATARPAPMVF WKVPRSGIENSTVTLSHPNGTTSVTSILHIKDPKNQVGKEVICQVLHLGTVTDFKQT VNKGPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:272) hGal9-GPI >ArtificialSequence;hGal9-GPI,DNA ATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGG ACTATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTC AGCTCCAGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGAC ATTGCCTTCCACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACG AGGCAGAACGGAAGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAG GGGATGCCCTTTGACCTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTG AACGGGATCCTCTTCGTGCAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACC ATCTCCGTCAATGGCTCTGTGCAGCTGTCCTACATCAGCTTCCAGAACCCCCGCACA GTCCCTGTTCAGCCTGCCTTCTCCACGGTGCCGTTCTCCCAGCCTGTCTGTTTCCCA CCCAGGCCCAGGGGGCGCAGACAAAAACCTCCCGGCGTGTGGCCTGCCAACCCGGCT CCCATTACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCT ACTCCCGCCATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATC ACCACCATTCTGGGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTC CTGCCCAGTGCTCAGAGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTC CACCTGAACCCCCGTTTTGATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAAC TCCTGGGGGTCTGAGGAGCGAAGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAG AGCTTCTCAGTGTGGATCTTGTGTGAAGCTCACTGCCTCAAGGTGGCCGTGGATGGT CAGCACCTGTTTGAATACTACCATCGCCTGAGGAACCTGCCCACCATCAACAGACTG GAAGTGGGGGGCGACATCCAGCTGACCCATGTGCAGACACCAAATAAAGGAAGTGGA ACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGT TTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:273) >ArtificialSequence;hGal9-GPI,AminoAcid MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGND IAFHFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMV NGILFVQYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFP PRPRGRRQKPPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFI TTILGGLYPSKSILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDN SWGSEERSLPRKMPFVRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRL EVGGDIQLTHVQTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:274) hHVEM-GPI >ArtificialSequence;hHVEM-GPI,DNA ATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGAC GTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCT CTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGC AGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAA CCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAG TGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACA GAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGAC CACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAG GGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCT CCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACG AAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTACCAAATAAAGGAAGTGGAACC ACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTG CTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:275) >ArtificialSequence;hHVEM-GPI,AminoAcid MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKC SPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRT ENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFS PNGTLEECQHQTKCSWLVTKAGAGTSSSHWVPNKGSGTTSGTTRLLSGHTCFTLTGL LGTLVTMGLLT (SEQIDNO:276) hPDL2-GPI >ArtificialSequence;hPDL2-GPI,DNA ATGATCTTCCTCCTGCTAATGTTGAGCCTGGAATTGCAGCTTCACCAGATAGCAGCT TTATTCACAGTGACAGTCCCTAAGGAACTGTACATAATAGAGCATGGCAGCAATGTG ACCCTGGAATGCAACTTTGACACTGGAAGTCATGTGAACCTTGGAGCAATAACAGCC AGTTTGCAAAAGGTGGAAAATGATACATCCCCACACCGTGAAAGAGCCACTTTGCTG GAGGAGCAGCTGCCCCTAGGGAAGGCCTCGTTCCACATACCTCAAGTCCAAGTGAGG GACGAAGGACAGTACCAATGCATAATCATCTATGGGGTCGCCTGGGACTACAAGTAC CTGACTCTGAAAGTCAAAGCTTCCTACAGGAAAATAAACACTCACATCCTAAAGGTT CCAGAAACAGATGAGGTAGAGCTCACCTGCCAGGCTACAGGTTATCCTCTGGCAGAA GTATCCTGGCCAAACGTCAGCGTTCCTGCCAACACCAGCCACTCCAGGACCCCTGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTAAAGCCACCCCCTGGCAGAAACTTC AGCTGTGTGTTCTGGAATACTCACGTGAGGGAACTTACTTTGGCCAGCATTGACCTT CAAAGTCAGATGGAACCCAGGACCCATCCAACTCCAAATAAAGGAAGTGGAACCACT TCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTT GGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:277) >ArtificialSequence;hPDL2-GPI,AminoAcid MIFLLLMLSLELQLHQIAALFTVTVPKELYIIEHGSNVTLECNFDTGSHVNLGAITA SLQKVENDTSPHRERATLLEEQLPLGKASFHIPQVQVRDEGQYQCIIIYGVAWDYKY LTLKVKASYRKINTHILKVPETDEVELTCQATGYPLAEVSWPNVSVPANTSHSRTPE GLYQVTSVLRLKPPPGRNFSCVFWNTHVRELTLASIDLQSQMEPRTHPTPNKGSGTT SGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:278) hTSG6-GPI >ArtificialSequence;hTSG6-GPI,DNA ATGATCATCTTAATTTACTTATTTCTCTTGCTATGGGAAGACACTCAAGGATGGGGA TTCAAGGATGGAATTTTTCATAACTCCATATGGCTTGAACGAGCAGCCGGTGTGTAC CACAGAGAAGCACGGTCTGGCAAATACAAGCTCACCTACGCAGAAGCTAAGGCGGTG TGTGAATTTGAAGGCGGCCATCTCGCAACTTACAAGCAGCTAGAGGCAGCCAGAAAA ATTGGATTTCATGTCTGTGCTGCTGGATGGATGGCTAAGGGCAGAGTTGGATACCCC ATTGTGAAGCCAGGGCCCAACTGTGGATTTGGAAAAACTGGCATTATTGATTATGGA ATCCGTCTCAATAGGAGTGAAAGATGGGATGCCTATTGCTACAACCCACACGCAAAG GAGTGTGGTGGCGTCTTTACAGATCCAAAGCAAATTTTTAAATCTCCAGGCTTCCCA AATGAGTACGAAGATAACCAAATCTGCTACTGGCACATTAGACTCAAGTATGGTCAG CGTATTCACCTGAGTTTTTTAGATTTTGACCTTGAAGATGACCCAGGTTGCTTGGCT GATTATGTTGAAATATATGACAGTTACGATGATGTCCATGGCTTTGTGGGAAGATAC TGTGGAGATGAGCTTCCAGATGACATCATCAGTACAGGAAATGTCATGACCTTGAAG TTTCTAAGTGATGCTTCAGTGACAGCTGGAGGTTTCCAAATCAAATATGTTGCAATG GATCCTGTATCCAAATCCAGTCAAGGAAAAAATACAAGTACTACTTCTACTGGAAAT AAAAACTTTTTAGCTGGAAGATTTAGCCACTTAATCGATCCAAATAAAGGAAGTGGA ACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGT TTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:279) >ArtificialSequence;hTSG6-GPI,AminoAcid MIILIYLFLLLWEDTQGWGFKDGIFHNSIWLERAAGVYHREARSGKYKLTYAEAKAV CEFEGGHLATYKQLEAARKIGFHVCAAGWMAKGRVGYPIVKPGPNCGFGKTGIIDYG IRLNRSERWDAYCYNPHAKECGGVFTDPKQIFKSPGFPNEYEDNQICYWHIRLKYGQ RIHLSFLDFDLEDDPGCLADYVEIYDSYDDVHGFVGRYCGDELPDDIISTGNVMTLK FLSDASVTAGGFQIKYVAMDPVSKSSQGKNTSTTSTGNKNFLAGRFSHLIDPNKGSG TTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:280) hHVEM-Fc-GPI >ArtificialSequence;hHVEM-Fc-GPI,DNA ATGGAGCCTCCTGGAGACTGGGGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGAC GTCTTGAGGCTGGTGCTGTATCTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCT CTGCCGTCCTGCAAGGAGGACGAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGC AGTCCAGGTTATCGTGTGAAGGAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAA CCCTGCCCTCCAGGCACCTACATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAG TGCCAAATGTGTGACCCAGCCATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACA GAGAACGCCGTGTGTGGCTGCAGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGAC CACTGCGCCGCGTGCCGCGCTTACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAG GGAGGCACCGAGAGTCAGGACACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCT CCCAATGGGACCCTGGAGGAATGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACG AAGGCCGGAGCTGGGACCAGCAGCTCCCACTGGGTAATCGATGACAAAACTCACACA TGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCC CCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTG GTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTG GAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGT GTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAG TGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCC AAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATG ACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATC GCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCC GTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGC AGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAAC CACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGA AGTGGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTG ACAGGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:281) >ArtificialSequence;hHVEM-Fc-GPI,AminoAcid MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSECCPKC SPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPAMGLRASRNCSRT ENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQDTLCQNCPPGTFS PNGTLEECQHQTKCSWLVTKAGAGTSSSHWVIDDKTHTCPPCPAPELLGGPSVELFP PKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTL TGLLGTLVTMGLLT (SEQIDNO:282) hPDL1-GPI-P2A- >ArtificialSequence;hPDL1-GPI-P2A-hHVEM-GPI,DNA hHVEM-GPI ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGCCAAATAAAGGAAGTGGAACCACTTCA GGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGG ACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTG AAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCTATGGAGCCTCCTGGAGACTGG GGGCCTCCTCCCTGGAGATCCACCCCCAAAACCGACGTCTTGAGGCTGGTGCTGTAT CTCACCTTCCTGGGAGCCCCCTGCTACGCCCCAGCTCTGCCGTCCTGCAAGGAGGAC GAGTACCCAGTGGGCTCCGAGTGCTGCCCCAAGTGCAGTCCAGGTTATCGTGTGAAG GAGGCCTGCGGGGAGCTGACGGGCACAGTGTGTGAACCCTGCCCTCCAGGCACCTAC ATTGCCCACCTCAATGGCCTAAGCAAGTGTCTGCAGTGCCAAATGTGTGACCCAGCC ATGGGCCTGCGCGCGAGCCGGAACTGCTCCAGGACAGAGAACGCCGTGTGTGGCTGC AGCCCAGGCCACTTCTGCATCGTCCAGGACGGGGACCACTGCGCCGCGTGCCGCGCT TACGCCACCTCCAGCCCGGGCCAGAGGGTGCAGAAGGGAGGCACCGAGAGTCAGGAC ACCCTGTGTCAGAACTGCCCCCCGGGGACCTTCTCTCCCAATGGGACCCTGGAGGAA TGTCAGCACCAGACCAAGTGCAGCTGGCTGGTGACGAAGGCCGGAGCTGGGACCAGC AGCTCCCACTGGGTACCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTT CTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATG GGCTTGCTGACTTAG (SEQIDNO:283) >ArtificialSequence;hPDL1-GPI-P2A-hHVEM-GPI,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNESLL KQAGDVEENPGPMEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKED EYPVGSECCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCDPA MGLRASRNCSRTENAVCGCSPGHFCIVQDGDHCAACRAYATSSPGQRVQKGGTESQD TLCQNCPPGTFSPNGTLEECQHQTKCSWLVTKAGAGTSSSHWVPNKGSGTTSGTTRL LSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:284) mCTLA4-Fc-GPI >ArtificialSequence;mCTLA4-Fc-GPI,DNA ATGGCTTGTCTTGGACTCCGGAGGTACAAAGCTCAACTGCAGCTGCCTTCTAGGACT TGGCCTTTTGTAGCCCTGCTCACTCTTCTTTTCATCCCAGTCTTCTCTGAAGCCATA CAGGTGACCCAACCTTCAGTGGTGTTGGCTAGCAGCCATGGTGTCGCCAGCTTTCCA TGTGAATATTCACCATCACACAACACTGATGAGGTCCGGGTGACTGTGCTGCGGCAG ACAAATGACCAAATGACTGAGGTCTGTGCCACGACATTCACAGAGAAGAATACAGTG GGCTTCCTAGATTACCCCTTCTGCAGTGGTACCTTTAATGAAAGCAGAGTGAACCTC ACCATCCAAGGACTGAGAGCTGTTGACACGGGACTGTACCTCTGCAAGGTGGAACTC ATGTACCCACCGCCATACTTTGTGGGCATGGGCAACGGGACGCAGATTTATGTCATT GATCCAGAACCATGCCCGGATTCTGAATCGATGACAAAACTCACACATGCCCACCGT GCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCA AGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGA GCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATA ATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCG TCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCT CCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGC CCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAGAACC AGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGT GGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACT CCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGC AGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTACACGC AGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGAACCA CTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGC TTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:285) >ArtificialSequence;mCTLA4-Fc-GPI,AminoAcid MACLGLRRYKAQLQLPSRTWPFVALLTLLFIPVFSEAIQVTQPSVVLASSHGVASFP CEYSPSHNTDEVRVTVLRQTNDQMTEVCATTFTEKNTVGFLDYPFCSGTFNESRVNL TIQGLRAVDTGLYLCKVELMYPPPYFVGMGNGTQIYVIDPEPCPDSD IDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKF NWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG KIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:286) mPDL1-C1C2 >ArtificialSequence;mPDL1-C1C2,DNA ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTATCGATGTCGAGCCACTGGGCATGGAG AATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTCTTG GGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTCAAT GCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTGCGG AGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCATGAG TACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTCATC CATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCGGTG CATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCCACG AGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAACGGA TGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACGGCC TCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTATGCA CGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAACGAT CAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAACTTG TTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCACAAC CGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG (SEQIDNO:287) >ArtificialSequence;mPDL1-C1C2,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWINSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTIDVEPLGMENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVN AWTPSSNDDNPWIQVNLLRRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFI HDVNKKHKEFVGNWNKNAVHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNG CANPLGLKNNSIPDKQITASSSYKTWGLHLFSWNPSYARLDKQGNENAWVAGSYGND QWLQIFPGNWDNHSHKKNLFETPILARYVRILPVAWHNRIALRLELLGC (SEQIDNO:288) mPDL1-Fc-GPI >ArtificialSequence;mPDL1-Fc-GPI,DNA ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTATCGATGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGG CAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTAC ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGTGGA ACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGT TTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:289) >ArtificialSequence;mPDL1-Fc-GPI,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGKIDPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:290) mPDL1-GPI >ArtificialSequence;mPDL1-GPI,DNA ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTCCAAATAAAGGAAGTGGAACCACTTCA GGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGG ACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:291) >ArtificialSequence;mPDL1-GPI,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWINSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:292) mPDL2-C1C2 >ArtificialSequence;mPDL2-C1C2,DNA ATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCT TTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTG AGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCC AGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTG GAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGA GATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTAC CTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTT CCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAA GTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTC AGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCT CTGAGTCGGATGGAACCCAAAGTCCCCAGAACGATCGATGTCGAGCCACTGGGCATG GAGAATGGGAACATTGCCAACTCACAGATCGCCGCCTCATCTGTGCGTGTGACCTTC TTGGGTTTGCAGCATTGGGTCCCGGAGCTGGCCCGCCTGAACCGCGCAGGCATGGTC AATGCCTGGACACCCAGCAGCAATGACGATAACCCCTGGATCCAGGTGAACCTGCTG CGGAGGATGTGGGTAACAGGTGTGGTGACGCAGGGTGCCAGCCGCTTGGCCAGTCAT GAGTACCTGAAGGCCTTCAAGGTGGCCTACAGCCTTAATGGACACGAATTCGATTTC ATCCATGATGTTAATAAAAAACACAAGGAGTTTGTGGGTAACTGGAACAAAAACGCG GTGCATGTCAACCTGTTTGAGACCCCTGTGGAGGCTCAGTACGTGAGATTGTACCCC ACGAGCTGCCACACGGCCTGCACTCTGCGCTTTGAGCTACTGGGCTGTGAGCTGAAC GGATGCGCCAATCCCCTGGGCCTGAAGAATAACAGCATCCCTGACAAGCAGATCACG GCCTCCAGCAGCTACAAGACCTGGGGCTTGCATCTCTTCAGCTGGAACCCCTCCTAT GCACGGCTGGACAAGCAGGGCAACTTCAACGCCTGGGTTGCGGGGAGCTACGGTAAC GATCAGTGGCTGCAGATCTTCCCTGGCAACTGGGACAACCACTCCCACAAGAAGAAC TTGTTTGAGACGCCCATCCTGGCTCGCTATGTGCGCATCCTGCCTGTAGCCTGGCAC AACCGCATCGCCCTGCGCCTGGAGCTGCTGGGCTGTTAG (SEQIDNO:293) >ArtificialSequence;mPDL2-C1C2,AminoAcid MLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRA SLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKY LTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPE GLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTIDVEPLGM ENGNIANSQIAASSVRVTFLGLQHWVPELARLNRAGMVNAWTPSSNDDNPWIQVNLL RRMWVTGVVTQGASRLASHEYLKAFKVAYSLNGHEFDFIHDVNKKHKEFVGNWNKNA VHVNLFETPVEAQYVRLYPTSCHTACTLRFELLGCELNGCANPLGLKNNSIPDKQIT ASSSYKTWGLHLFSWNPSYARLDKQGNFNAWVAGSYGNDQWLQIFPGNWDNHSHKKN LFETPILARYVRILPVAWHNRIALRLELLGC (SEQIDNO:294) mPDL2-Fc-GPI >ArtificialSequence;mPDL2-Fc-GPI,DNA ATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCT TTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTG AGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCC AGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTG GAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGA GATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTAC CTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTT CCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAA GTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTC AGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCT CTGAGTCGGATGGAACCCAAAGTCCCCAGAACGATCGATGACAAAACTCACACATGC CCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCA AAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTG GACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAG GTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTG GTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGC AAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAA GGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACC AAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCC GTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTG CTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGG TGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCAC TACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATCCAAATAAAGGAAGT GGAACCACTTCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACA GGTTTGCTTGGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:295) >ArtificialSequence;mPDL2-Fc-GPI,AminoAcid MLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRA SLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKY LTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPE GLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTIDDKTHTC PPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKENWYVDGVE VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKIDPNKGS GTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:296) mPDL1-mFc-GPI >ArtificialSequence;mPDL1-mFc-GPI,DNA ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTGGTTGTAAGCCTTGCATATGTACAGTC CCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATT ACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAG GTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCC CGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCAC CAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCT GCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTG TACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGC ATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAG CCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTC GTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACC TGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAACCAAATAAAGGAAGTGGAACCACTTCAGGTACTACCCGTCTTCTA TCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACGCTAGTAACCATGGGC TTGCTGACTTAG (SEQIDNO:297) >ArtificialSequence;mPDL1-mFc-GPI,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPE VQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFP APIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQ PAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:298) mPDL2-GPI >ArtificialSequence;mPDL2-GPI,DNA ATGCTGCTCCTGCTGCCGATACTGAACCTGAGCTTACAACTTCATCCTGTAGCAGCT TTATTCACCGTGACAGCCCCTAAAGAAGTGTACACCGTAGACGTCGGCAGCAGTGTG AGCCTGGAGTGCGATTTTGACCGCAGAGAATGCACTGAACTGGAAGGGATAAGAGCC AGTTTGCAGAAGGTAGAAAATGATACGTCTCTGCAAAGTGAAAGAGCCACCCTGCTG GAGGAGCAGCTGCCCCTGGGAAAGGCTTTGTTCCACATCCCTAGTGTCCAAGTGAGA GATTCCGGGCAGTACCGTTGCCTGGTCATCTGCGGGGCCGCCTGGGACTACAAGTAC CTGACGGTGAAAGTCAAAGCTTCTTACATGAGGATAGACACTAGGATCCTGGAGGTT CCAGGTACAGGGGAGGTGCAGCTTACCTGCCAGGCTAGAGGTTATCCCCTAGCAGAA GTGTCCTGGCAAAATGTCAGTGTTCCTGCCAACACCAGCCACATCAGGACCCCCGAA GGCCTCTACCAGGTCACCAGTGTTCTGCGCCTCAAGCCTCAGCCTAGCAGAAACTTC AGCTGCATGTTCTGGAATGCTCACATGAAGGAGCTGACTTCAGCCATCATTGACCCT CTGAGTCGGATGGAACCCAAAGTCCCCAGAACGCCAAATAAAGGAAGTGGAACCACT TCAGGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTT GGGACGCTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:299) >ArtificialSequence;mPDL2-GPI,AminoAcid MLLLLPILNLSLQLHPVAALFTVTAPKEVYTVDVGSSVSLECDFDRRECTELEGIRA SLQKVENDTSLQSERATLLEEQLPLGKALFHIPSVQVRDSGQYRCLVICGAAWDYKY LTVKVKASYMRIDTRILEVPGTGEVQLTCQARGYPLAEVSWQNVSVPANTSHIRTPE GLYQVTSVLRLKPQPSRNFSCMFWNAHMKELTSAIIDPLSRMEPKVPRTPNKGSGTT SGTTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:300) mPDL1-GPI-P2A- >ArtificialSequence;mPDL1-GPI-P2A-mHVEM-GPI,DNA mHVEM-GPI ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTCCAAATAAAGGAAGTGGAACCACTTCA GGTACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGG ACGCTAGTAACCATGGGCTTGCTGACTGGAAGCGGAGCTACTAACTTCAGCCTGCTG AAGCAGGCTGGCGACGTGGAGGAGAACCCTGGACCTATGGAACCTCTCCCAGGATGG GGGTCGGCACCCTGGAGCCAGGCCCCTACAGACAACACCTTCAGGCTGGTGCCTTGT GTCTTCCTTTTGAACTTGCTGCAGCGCATCTCTGCCCAGCCCTCATGCAGACAGGAG GAGTTCCTTGTGGGAGACGAGTGCTGCCCCATGTGCAACCCAGGTTACCATGTGAAG CAGGTCTGCAGTGAGCATACAGGCACAGTGTGTGCCCCCTGTCCCCCACAGACATAT ACCGCCCATGCAAATGGCCTGAGCAAGTGTCTGCCCTGCGGAGTCTGTGATCCAGAC ATGGGCCTGCTGACCTGGCAGGAGTGCTCCAGCTGGAAGGACACTGTGTGCAGATGC ATCCCAGGCTACTTCTGTGAGAACCAGGATGGGAGCCACTGTTCCACATGCTTGCAG CACACCACCTGCCCTCCAGGGCAGAGGGTAGAGAAGAGAGGGACTCACGACCAGGAC ACTGTATGTGCTGACTGCCTAACAGGGACCTTCTCACTTGGAGGGACTCAGGAGGAA TGCCTGCCCTGGACCAACTGCAGTGCATTTCAACAGGAAGTAAGACGTGGGACCAAC AGCACAGACACCACCTGCTCCTCCCAGCCAAATAAAGGAAGTGGAACCACTTCAGGT ACTACCCGTCTTCTATCTGGGCACACGTGTTTCACGTTGACAGGTTTGCTTGGGACG CTAGTAACCATGGGCTTGCTGACTTAG (SEQIDNO:301) >ArtificialSequence;mPDL1-GPI-P2A-mHVEM-GPI,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTPNKGSGTTSGTTRLLSGHTCFTLTGLLGTLVTMGLLTGSGATNFSLL KQAGDVEENPGPMEPLPGWGSAPWSQAPTDNTFRLVPCVFLLNLLQRISAQPSCRQE EFLVGDECCPMCNPGYHVKQVCSEHTGTVCAPCPPQTYTAHANGLSKCLPCGVCDPD MGLLTWQECSSWKDTVCRCIPGYFCENQDGSHCSTCLQHTTCPPGQRVEKRGTHDQD TVCADCLTGTFSLGGTQEECLPWTNCSAFQQEVRRGINSTDTTCSSQPNKGSGTTSG TTRLLSGHTCFTLTGLLGTLVTMGLLT (SEQIDNO:302) hPDL1-ADAM10 >ArtificialSequence;hPDL1-ADAM10,DNA ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGTGTGGAAATGGAATGGTAGAACAAGGT GAAGAATGTGATTGTGGCTATAGTGACCAGTGTAAAGATGAATGCTGCTTCGATGCA AATCAACCAGAGGGAAGAAAATGCAAACTGAAACCTGGGAAACAGTGCAGTCCAAGT CAAGGTCCTTGTTGTACAGCACAGTGTGCATTCAAGTCAAAGTCTGAGAAGTGTCGG GATGATTCAGACTGTGCAAGGGAAGGAATATGTAATGGCTTCACAGCTCTCTGCCCA GCATCTGACCCTAAACCAAACTTCACAGACTGTAATAGGCATACACAAGTGTGCATT AATGGGCAATGTGCAGGTTCTATCTGTGAGAAATATGGCTTAGAGGAGTGTACGTGT GCCAGTTCTGATGGCAAAGATGATAAAGAATTATGCCATGTATGCTGTATGAAGAAA ATGGACCCATCAACTTGTGCCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGT GGTCGAACCATCACCCTGCAACCTGGATCCCCTTGCAACGATTTTAGAGGTTACTGT GATGTTTTCATGCGGTGCAGATTAGTAGATGCTGATGGTCCTCTAGCTAGGCTTAAA AAAGCAATTTTTAGTCCAGAGCTCTATGAAAACATTGCTGAATGGATTGTGGCTCAT TGGTGGGCAGTATTACTTATGGGAATTGCTCTGATCATGCTAATGGCTGGATTTATT AAGATATGCAGTGTTCATACTCCAAGTAGTAATCCAAAGTTGCCTCCTCCTAAACCA CTTCCAGGCACTTTAAAGAGGAGGAGACCTCCACAGCCCATTCAGCAACCCCAGCGT CAGCGGCCCCGAGAGAGTTATCAAATGGGACACATGAGACGCTAA (SEQIDNO:303) >ArtificialSequence;hPDL1-ADAM10,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERCGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPS QGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNETDCNRHTQVCI NGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHES GRTITLQPGSPCNDERGYCDVEMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAH WWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQR QRPRESYQMGHMRR (SEQIDNO:304) hPDL1-4Fc- >ArtificialSequence;hPDL1-4Fc-CD9tm2,DNA CD9tm2 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGGAGTCCAAATATGGTCCCCCATGCCCA TCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTC AGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAG GTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG CAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC ACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAATTCTACACAGGAGTCTATATTCTG ATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTG CAGGAGTCCCAGTGC (SEQIDNO:305) >ArtificialSequence;hPDL1-4Fc-CD9tm2,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLENVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCK VSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVESCSVMHEALHNHY TQKSLSLSPGKFYTGVYILIGAGALMMLVGELGCCGAVQESQCVIM (SEQIDNO:306) hPDL1-4Fc- >ArtificialSequence;hPDL1-4Fc-CD9tm2-KRAS,DNA CD9tm2- ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modifiedKRas ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGGAGTCCAAATATGGTCCCCCATGCCCA TCATGCCCAGCACCTGAGTTCCTGGGGGGACCATCAGTCTTCCTGTTCCCCCCAAAA CCCAAGGACACTCTCATGATCTCCCGGACCCCTGAGGTCACGTGCGTGGTGGTGGAC GTGAGCCAGGAAGACCCCGAGGTCCAGTTCAACTGGTACGTGGATGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTTCAACAGCACGTACCGTGTGGTC AGGGTCCTCACCGTCCTGCACCAGGACTGGCTGAACGGTAAGGAGTACAAGTGCAAG GTCTCCAACAAAGGCCTCCCGTCCTCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAGCCACAGGTGTACACCCTGCCCCCATCCCAGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTACCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGGACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAGGCTAACCGTGGACAAGAGCAGGTGG CAGGAGGGGAATGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTAC ACACAGAAGAGCCTCTCCCTGTCTCCGGGTAAATTCTACACAGGAGTCTATATTCTG ATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTG CAGGAGTCCCAGTGCAAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATG TAA (SEQIDNO:307) >ArtificialSequence;hPDL1-4Fc-CD9tm2-KRAS,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVRVLTVLHQDWLNGKEYKCK VSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPEDNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVESCSVMHEALHNHY TQKSLSLSPGKFYTGVYILIGAGALMMLVGELGCCGAVQESQCKKKKKKKKTKCVIM (SEQIDNO:308) hPDL1-Fc- >ArtificialSequence;hPDL1-Fc-CD9tm2,DNA CD9tm2 ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGG CAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTAC ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATTTCTACACAGGAGTCTAT ATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGG GCTGTGCAGGAGTCCCAGTGCGTAATTATGTAA (SEQIDNO:309) >ArtificialSequence;hPDL1-Fc-CD9tm2,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWINGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGKIDFYTGVYILIGAGALMMLVGELGCCGAVQESQCVIM (SEQIDNO:310) hPDL1-Fc- >ArtificialSequence;hPDL1-Fc-CD9tm2-KRAS,DNA CD9tm2- ATGAGGATATTTGCTGTCTTTATATTCATGACCTACTGGCATTTGCTGAACGCATTT modifiedKRAS ACTGTCACGGTTCCCAAGGACCTATATGTGGTAGAGTATGGTAGCAATATGACAATT GAATGCAAATTCCCAGTAGAAAAACAATTAGACCTGGCTGCACTAATTGTCTATTGG GAAATGGAGGATAAGAACATTATTCAATTTGTGCATGGAGAGGAAGACCTGAAGGTT CAGCATAGTAGCTACAGACAGAGGGCCCGGCTGTTGAAGGACCAGCTCTCCCTGGGA AATGCTGCACTTCAGATCACAGATGTGAAATTGCAGGATGCAGGGGTGTACCGCTGC ATGATCAGCTATGGTGGTGCCGACTACAAGCGAATTACTGTGAAAGTCAATGCCCCA TACAACAAAATCAACCAAAGAATTTTGGTTGTGGATCCAGTCACCTCTGAACATGAA CTGACATGTCAGGCTGAGGGCTACCCCAAGGCCGAAGTCATCTGGACAAGCAGTGAC CATCAAGTCCTGAGTGGTAAGACCACCACCACCAATTCCAAGAGAGAGGAGAAGCTT TTCAATGTGACCAGCACACTGAGAATCAACACAACAACTAATGAGATTTTCTACTGC ACTTTTAGGAGATTAGATCCTGAGGAAAACCATACAGCTGAATTGGTCATCCCAGAA CTACCTCTGGCACATCCTCCAAATGAAAGGATCGATGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAA CCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGAC GTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTG CATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTC AGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAG GTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGG CAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGAGGAGATGACCAAG AACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTG GAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTG GACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGG CAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCACGAGGCTCTGCACAACCACTAC ACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAAATCGATTTCTACACAGGAGTCTAT ATTCTGATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGG GCTGTGCAGGAGTCCCAGTGCAAAAAGAAGAAAAAGAAGAAGAAGACAAAGTGTGTA ATTATGTAA (SEQIDNO:311) >ArtificialSequence;hPDL1-Fc-CD9tm2-KRAS,AminoAcid MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYW EMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRC MISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSD HQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPE LPLAHPPNERIDDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSHEDPEVKENWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPGKIDFYTGVYILIGAGALMMLVGFLGCCGAVQESQCKKKKKKKKTKCV IM (SEQIDNO:312) mPDL1-mFc- >ArtificialSequence;mPDL1-mFc-CD9tm2,DNA CD9tm2 ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTGGTTGTAAGCCTTGCATATGTACAGTC CCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATT ACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAG GTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCC CGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCAC CAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCT GCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTG TACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGC ATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAG CCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTC GTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACC TGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAATTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATG ATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCGTAATT ATGTAA (SEQIDNO:313) >ArtificialSequence;mPDL1-mFc-CD9tm2,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWINSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPE VQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFP APIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQ PAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKFYTGVYILIGAGALMMLVGFLGCCGAVQESQCVIM (SEQIDNO:314) mPDL1-mFc- >ArtificialSequence;mPDL1-mFc-CD9tm2-KRAS,DNA CD9tm2- ATGAGGATATTTGCTGGCATTATATTCACAGCCTGCTGTCACTTGCTACGGGCGTTT modifiedKRAS ACTATCACGGCTCCAAAGGACTTGTACGTGGTGGAGTATGGCAGCAACGTCACGATG GAGTGCAGATTCCCTGTAGAACGGGAGCTGGACCTGCTTGCGTTAGTGGTGTACTGG GAAAAGGAAGATGAGCAAGTGATTCAGTTTGTGGCAGGAGAGGAGGACCTTAAGCCT CAGCACAGCAACTTCAGGGGGAGAGCCTCGCTGCCAAAGGACCAGCTTTTGAAGGGA AATGCTGCCCTTCAGATCACAGACGTCAAGCTGCAGGACGCAGGCGTTTACTGCTGC ATAATCAGCTACGGTGGTGCGGACTACAAGCGAATCACGCTGAAAGTCAATGCCCCA TACCGCAAAATCAACCAGAGAATTTCCGTGGATCCAGCCACTTCTGAGCATGAACTA ATATGTCAGGCCGAGGGTTATCCAGAAGCTGAGGTAATCTGGACAAACAGTGACCAC CAACCCGTGAGTGGGAAGAGAAGTGTCACCACTTCCCGGACAGAGGGGATGCTTCTC AATGTGACCAGCAGTCTGAGGGTCAACGCCACAGCGAATGATGTTTTCTACTGTACG TTTTGGAGATCACAGCCAGGGCAAAACCACACAGCGGAGCTGATCATCCCAGAACTG CCTGCAACACATCCTCCACAGAACAGGACTGGTTGTAAGCCTTGCATATGTACAGTC CCAGAAGTATCATCTGTCTTCATCTTCCCCCCAAAGCCCAAGGATGTGCTCACCATT ACTCTGACTCCTAAGGTCACGTGTGTTGTGGTAGACATCAGCAAGGATGATCCCGAG GTCCAGTTCAGCTGGTTTGTAGATGATGTGGAGGTGCACACAGCTCAGACGCAACCC CGGGAGGAGCAGTTCAACAGCACTTTCCGCTCAGTCAGTGAACTTCCCATCATGCAC CAGGACTGGCTCAATGGCAAGGAGTTCAAATGCAGGGTCAACAGTGCAGCTTTCCCT GCCCCCATCGAGAAAACCATCTCCAAAACCAAAGGCAGACCGAAGGCTCCACAGGTG TACACCATTCCACCTCCCAAGGAGCAGATGGCCAAGGATAAAGTCAGTCTGACCTGC ATGATAACAGACTTCTTCCCTGAAGACATTACTGTGGAGTGGCAGTGGAATGGGCAG CCAGCGGAGAACTACAAGAACACTCAGCCCATCATGGACACAGATGGCTCTTACTTC GTCTACAGCAAGCTCAATGTGCAGAAGAGCAACTGGGAGGCAGGAAATACTTTCACC TGCTCTGTGTTACATGAGGGCCTGCACAACCACCATACTGAGAAGAGCCTCTCCCAC TCTCCTGGTAAATTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTCATG ATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCAAAAAG AAGAAAAAGAAGAAGAAGACAAAGTGTGTAATTATGTAA (SEQIDNO:315) >ArtificialSequence;mPDL1-mFc-CD9tm2-KRAS,AminoAcid MRIFAGIIFTACCHLLRAFTITAPKDLYVVEYGSNVTMECRFPVERELDLLALVVYW EKEDEQVIQFVAGEEDLKPQHSNFRGRASLPKDQLLKGNAALQITDVKLQDAGVYCC IISYGGADYKRITLKVNAPYRKINQRISVDPATSEHELICQAEGYPEAEVIWTNSDH QPVSGKRSVTTSRTEGMLLNVTSSLRVNATANDVFYCTFWRSQPGQNHTAELIIPEL PATHPPQNRTGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVVVDISKDDPE VQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLNGKEFKCRVNSAAFP APIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCMITDFFPEDITVEWQWNGQ PAENYKNTQPIMDTDGSYFVYSKLNVQKSNWEAGNTFTCSVLHEGLHNHHTEKSLSH SPGKFYTGVYILIGAGALMMLVGFLGCCGAVQESQCKKKKKKKKTKCVIM (SEQIDNO:316)
[0143] In some embodiments of any of the aspects, the fusion polypeptides provided herein comprise two or more POI domains. The specific combinations of POI domains can be used to regulate inflammatory immune responses. Non-limiting examples of additive and synergistic combinations of POIs that can modulate inflammatory signaling pathways are provided in Table 5 (below).
TABLE-US-00007 TABLE 5 Exemplary POI combinations and combined targets for modulating inflammation. COMBINED PUTATIVE ADDITIVE or POIs (LIGANDS) TARGETS SYNERGISTIC MOA PD-L1 or PD-L2 PD-1 Differential use of Shp HVEM BTLA phosphatases. BTLA inhibits both TCR and CD28 phosphorylation (via Shp1) while PD-1 inhibits CD28 phosphorylation (via Shp2). PD-L1 or PD-L2 PD-1 LAG-3 exerts differential FGL1 LAG-3 inhibitory impacts on various types of lymphocytes and shows synergy with PD-1 to inhibit immune responses. PD-L1 or PD-L2 PD-1 PD-1 and Tim-3 have non- CEACAM-1 or TIM-3 redundant downstream signaling GAL9 mechanisms. PD-L1 or PD-L2 PD-1 Differential use of Shp CD155 TIGIT phosphatases. Non-redundantly regulate T cell responses. PD-L1 or PD-L2 PD-1 PD-1 and VISTA non- VSIG3 VISTA redundantly regulate T cell responses. VISTA contains cytosolic SH3 binding domains for adapter proteins. CEACAM-1 or GAL9 TIM-3 TIGIT and TIM-3 have non- CD155 TIGIT redundant downstream signaling mechanisms. PD-L1 or PD-L2 PD-1 PD-1, LAG-3 and TIM-3 have FGL1 LAG-3 non-redundant downstream CEACAM-1 or GAL9 TIM-3 signaling mechanisms.
Methods of Preparing Extracellular Vesicle Compositions
[0144] In another aspect, provided herein is a method of preparing an engineered extracellular vesicle provided herein. Generally, the method comprises providing a population of cells expressing a vector construct encoding one or more sticky binder (vesicle targeting domain) and one or more signaling domains (POI domain).
[0145] The EVs provided herein can be isolated and purified form any biological source, e.g., cells. The cells that produce the engineered EVs provided herein can be from any viable non-human source or organism. Usually the organism is an animal, vertebrate, or mammal. In some embodiments, the cell described herein is from a human. The cells described herein can be from any tissue isolated from an organism by methods known in the art. The scientific literature provides guidance for one of ordinary skill in the art to isolate, prepare, and culture cells as necessary for use in the compositions and methods described herein. One of skill in the art can appreciate that the cell source of the EVs may alter the cellular protein expression and the native or endogenous cargo within the EV. It is contemplated herein that this can be leveraged for therapeutic effect depending on the disease or disorder being treated.
[0146] In some embodiments, the population of cells has been altered by exposure to environmental conditions (e.g., hypoxia), small molecule addition, presence/absence of exogenous factors (e.g., growth factors, cytokines) at the time, or substantially contemporaneous with, isolating the plurality of artificial synapses in a manner altering the regulatory state of the cell. In various embodiments, the cells are HEK 293 cells, MSCs, PER.C, fibrosarcoma HT-1080 or HuH7 cell lines.
[0147] The method comprises providing a population of cells and culturing the cells in serum-free or un-concentrated conditioned medium. This includes, for example, artificial synapses secreted into media as conditioned by a population of cells in culture, further including cell lines capable of serial passaging. In certain embodiments, the cells in culture are grown to 10, 20, 30, 40, 50, 60, 70, 80, 90, or 90% or more confluency when artificial synapses (engineered EVs) are isolated.
[0148] The methods provided herein further comprise contacting the cells provided herein with a nucleic acid vector encoding the at least one fusion polypeptide provided herein. The vector can be added to the cell culture medium of the cells by methods known in the art and discussed further below.
[0149] A vector is a nucleic acid construct designed for delivery to a host cell or for transfer of genetic material between different host cells. As used herein, a vector can be viral or non-viral. The term vector encompasses any genetic element that is capable of replication when associated with the proper control elements and that can transfer genetic material to cells. A vector can include, but is not limited to, a cloning vector, an expression vector, a plasmid, phage, transposon, cosmid, artificial chromosome, virus, virion, etc. In some embodiments of any of the aspects, the vector is selected from the group consisting of: a plasmid, a cosmid and a viral vector.
[0150] Expression refers to the cellular processes involved in producing RNA and proteins and as appropriate, secreting proteins, including where applicable, but not limited to, for example, transcription, transcript processing, translation and protein folding, modification and processing. Expression products include RNA transcribed from a gene, and polypeptides obtained by translation of mRNA transcribed from a gene.
[0151] In some embodiments, a vector is capable of driving expression of one or more sequences in a mammalian cell; i.e., the vector is a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMIBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are typically provided by one or more regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, simian virus 40, and others disclosed herein and known in the art. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.
[0152] In some embodiments, the recombinant expression vector is capable of directing expression of the exogenous fusion polypeptide nucleic acid sequence preferentially in a particular cell type (e.g., via tissue-specific regulatory elements).
[0153] Tissue-specific and inducible regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. hnmunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the -fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).
[0154] In some embodiments, the at least one nucleic acid sequence described herein is delivered to the cell described herein via an integrating vector. Integrating vectors have their delivered genetic material (or a copy of it) permanently incorporated into a host cell chromosome. Non-integrating vectors remain episomal which means the nucleic acid contained therein is never integrated into a host cell chromosome. Examples of integrating vectors include retroviral vectors, lentiviral vectors, hybrid adenoviral vectors, and herpes simplex viral vectors.
[0155] In some embodiments, the at least one nucleic acid sequence described herein is delivered to the cell described herein via a non-integrative vector. Non-integrative vectors include non-integrative viral vectors. Non-integrative viral vectors eliminate one of the primary risks posed by integrative retroviruses, as they do not incorporate their genome into the host DNA. One example is the Epstein Barr oriP/Nuclear Antigen-1 (EBNA1) vector, which is capable of limited self-replication and known to function in mammalian cells. Containing two elements from Epstein-Barr virus, oriP and EBNA1, binding of the EBNA1 protein to the virus replicon region oriP maintains a relatively long-term episomal presence of plasmids in mammalian cells. This particular feature of the oriP/EBNA1 vector makes it ideal for generation of integration-free host cells. Other non-integrative viral vectors include adenoviral vectors and the adeno-associated viral (AAV) vectors.
[0156] Another non-integrative viral vector is RNA Sendai viral vector, which can produce protein without entering the nucleus of an infected cell. The F-deficient Sendai virus vector remains in the cytoplasm of infected cells for a few passages, but is diluted out quickly and completely lost after several passages (e.g., 10 passages). This permits a self-limiting transient expression of a chosen heterologous gene or genes in a target cell. This aspect can be helpful, e.g., for the transient introduction of reprogramming factors, among other uses. As noted above, in some embodiments, the nucleic acid sequence described herein is expressed in the cells from a viral vector.
[0157] A viral vector includes a nucleic acid vector construct that includes at least one element of viral origin and has the capacity to be packaged into a viral vector particle. The viral vector can contain a nucleic acid encoding a polypeptide described herein in place of non-essential viral genes. The vector and/or particle can be utilized for the purpose of transferring nucleic acids into cells either in vitro or in vivo.
[0158] The nucleic acids described herein can be delivered using any transfection reagent or other physical means that facilitates entry of nucleic acids into a cell. Methods of non-viral delivery of nucleic acids include lipofection, nucleofection, microinjection, electroporation, biolistics, virosomes, liposomes, immunoliposomes, polycation or lipid:nucleic acid conjugates, naked DNA, artificial virions, and agent-enhanced uptake of DNA. Lipofection is described in e.g., U.S. Pat. Nos. 5,049,386, 4,946,787; and 4,897,355) and lipofection reagents are sold commercially (e.g., Transfectam and Lipofectin) Cationic and neutral lipids that are suitable for efficient receptor-recognition lipofection of polynucleotides include those of Felgner, WO 91/17424; WO 91/16024. Delivery can be to cells (e.g., in vitro or ex vivo administration) or target tissues (e.g., in vivo administration).
[0159] The preparation of lipid:nucleic acid complexes, including targeted liposomes such as immunolipid complexes, is well known to one of skill in the art (see, e.g., Crystal, Science 270:404-410 (1995); Blaese et al., Cancer Gene Ther. 2:291-297 (1995); Behr et al., Bioconjugate Chem. 5:382-389 (1994); Remy et al., Bioconjugate Chem. 5:647-654 (1994); Gao et al., Gene Therapy 2:710-722 (1995); Ahmad et al., Cancer Res. 52:4817-4820 (1992); U.S. Pat. Nos. 4,186,183, 4,217,344, 4,235,871, 4,261,975, 4,485,054, 4,501,728, 4,774,085, 4,837,028, and 4,946,787).
[0160] An agent that increases cellular uptake is a molecule that facilitates transport of a molecule, e.g., nucleic acid, or peptide or polypeptide, or other molecule that does not otherwise efficiently transit the cell membrane across a lipid membrane. For example, a nucleic acid can be conjugated to a lipophilic compound (e.g., cholesterol, tocopherol, etc.), a cell penetrating peptide (CPP) (e.g., penetratin, TAT, Syn1B, etc.), or a polyamine (e.g., spermine). Further examples of agents that increase cellular uptake are disclosed, for example, in Winkler (2013). Oligonucleotide conjugates for therapeutic applications. Ther. Deliv. 4(7); 791-809. The one or more nucleic acid sequences encoding the fusion polypeptides provided herein can be delivered to the cell by any method discussed above or known in the art.
[0161] In some embodiments of any of the aspects, the vectors provided herein comprise a nucleic acid modification by methods known in the art. In some embodiments, the cell can be genetically manipulated to express one or more vectors, each encoding one or more vesicle targeting domains and/or one or more signaling domains. In certain embodiments, the population of cells has been genetically manipulated. This includes, for example, knockout (KO) or transgenic (TG) cell lines, wherein an endogenous gene has been removed and/or an exogenous introduced in a stable, persistent manner. In certain embodiments, this further includes transient knockdown of one or more genes and associated coding and non-coding transcripts within the population of cells, via any number of methods known in the art, such as introduction of dsRNA, siRNA, microRNA, etc. This further includes transient expression of one or more genes and associated coding and non-coding transcripts within the population of cells, via any number of methods known in the art, such as introduction of a vector, plasmid, artificial plasmid, replicative and/or non-replicative virus, etc.
[0162] In certain embodiments the cell population has been manipulated to knockout the expression of one or more endogenous gene sequences that encode for metalloendopeptidases. In certain embodiments the cell population has been manipulated to knockout the expression of one or more endogenous gene sequences that code for metalloproteinases. In certain embodiments the cell population has been manipulated to knockout the expression of one or more endogenous gene sequences that encode for a disintegrin and metalloproteinase (ADAM). For example, the cell population can be manipulated to knock of the expression of one or more gene sequences that encode for ADAM1, ADAM2, ADAM7, ADAM8, ADAM9, ADAM10, ADAM11, ADAM12, ADAM15, ADAM17, ADAM18, ADAM19, ADAM20, ADAM21, ADAM22, ADAM23, ADAM28, ADAM29, ADAM30, ADAM33, etc.
[0163] In certain embodiments the cell population has been manipulated to knockout the expression of one or more endogenous genes that encode for enzymes that hydrolyze the inositol phosphate linkage in proteins anchored by phosphatidylinositol glycans, thereby preventing the release of proteins attached to the plasma membrane via GPI anchors. For example, the cell population can be manipulated to knock of the expression of phosphatidylinositol-glycan-specific phospholipase D (GPLD1).
[0164] In certain embodiments, the population of cells has been genetically manipulated. This includes, for example, knock-in of an exogenous genetic sequence, wherein the exogenous genetic sequence is expressed in a stable, persistent manner. In certain embodiments the cell population has been manipulated to knock-in a recombinase recognition sequences (e.g., FRT), transgenic reporters such as antibiotic resistance genes, fluorescent or enzymatic reporter genes, etc. or the like known in the art.
[0165] In some embodiments, the method comprises a step of isolating the engineered extracellular vesicles provided herein. Particulates within the medium are removed by a series of specific centrifugation steps and the media is filtered. The general method of isolating extracellular vesicles as provided herein is depicted in
[0166] In some embodiments, isolating the plurality of engineered EVs (artificial synapses) includes precipitation, centrifugation, filtration, immuno-separation, tangential flow, liquid chromatography, and/or flow fractionation. For example, differential ultracentrifugation has become a technique wherein secreted exosomes are isolated from the supernatants of cultured cells. This approach allows for separation of exosomes from non-membranous particles, by exploiting their relatively low buoyant density. Size exclusion allows for their separation from biochemically similar, but biophysically different microvesicles, which possess larger diameters of up to 1,000 nm. Differences in floatation velocity further allows for separation of differentially sized exosomes. In general, exosome sizes will possess a diameter ranging from 30-300 nm, including sizes of 30-150 nm. Further purification may rely on specific properties of the particular exosomes of interest. This includes, for example, use of immunoadsorption with a protein of interest to select specific vesicles with exoplasmic or outward orientations.
[0167] Among current methods (differential centrifugation, discontinuous density gradients, immunoaffinity, ultrafiltration and liquid chromatography (e.g., fast protein liquid chromatography (FPLC)), differential ultracentrifugation is the most commonly used for exosome isolation. This technique utilizes increasing centrifugal force from 2000 xg to 10,000 xg to separate the medium- and larger-sized particles and cell debris from the exosome pellet at 100,000 xg. Centrifugation alone allows for significant separation/collection of exosomes from a conditioned medium, although it is insufficient to remove various protein aggregates, genetic materials, particulates from media and cell debris that are common contaminants. Enhanced specificity of exosome purification may deploy sequential centrifugation in combination with ultrafiltration, or equilibrium density gradient centrifugation in a sucrose density gradient, to provide for the greater purity of the exosome preparation (flotation density 1.1-1.2 g/ml) or application of a discrete sugar cushion in preparation.
[0168] Ultrafiltration can be used to purify exosomes without compromising their biological activity. Membranes with different pore sizessuch as 100 kDa molecular weight cut-off (MWCO) or 300 kDa MWCO and gel filtration to eliminate smaller particleshave been used to avoid the use of a nonneutral pH or non-physiological salt concentration. Currently available tangential flow filtration (TFF) systems are scalable (to >10,000 L), allowing one to not only purify, but concentrate the exosome fractions, and such approaches are less time consuming than differential centrifugation. Liquid Chromatography can also be used to purify exosomes to homogeneously sized particles and preserve their biological activity as the preparation is maintained at a physiological pH and salt concentration.
[0169] Other chemical methods have exploit differential solubility of exosomes for precipitation techniques, addition to volume-excluding polymers (e.g., polyethylene glycols (PEGs)), possibly combined additional rounds of centrifugation or filtration. For example, a precipitation reagent, ExoQuick, can be added to conditioned cell media to quickly and rapidly precipitate a population of exosomes, although re-suspension of pellets prepared via this technique may be difficult. Flow field-flow fractionation (FlFFF) is an elution-based technique that is used to separate and characterize macromolecules (e.g., proteins) and nano- to micro-sized particles (e.g., organelles and cells) and which has been successfully applied to fractionate exosomes from culture media.
[0170] Beyond these techniques relying on general biochemical and biophysical features, focused techniques may be applied to isolated specific exosomes of interest. This includes relying on antibody immunoaffinity to recognizing certain exosome-associated antigens. Conjugation to magnetic beads, chromatography matrices, plates or microfluidic devices allows isolating of specific exosome populations of interest as may be related to their production from a parent cell of interest or associated cellular regulatory state. Other affinity-capture methods use lectins which bind to specific saccharide residues on the exosome surface.
[0171] In several embodiments, isolating a plurality of artificial synapses from the population of cells includes centrifugation of the cells and/or media conditioned by the cells. In several embodiments, ultracentrifugation is used. In several embodiments, isolating a plurality of artificial synapses from the population of cells is via size-exclusion filtration. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of discontinuous density gradients, immunoaffinity, ultrafiltration, tangential flow and/or liquid chromatography.
[0172] In certain embodiments, differential ultracentrifugation includes using centrifugal force from 1000-2000 xg, 2000-3000 xg, 3000-4000 xg, 4000-5000 xg, 5000 xg-6000 xg, 6000-7000 xg, 7000-8000 xg, 8000-9000 xg, 9000-10,000 xg, to 10,000 xg or more to separate larger-sized particles from a plurality of artificial synapses derived from the cells.
[0173] In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of filtration or ultrafiltration. In certain embodiments, a size exclusion membrane with different pore sizes is used. For example, a size exclusion membrane can include use of a filter with a pore size of 0.1-0.5 micron (m), 0.5-1.0 m, 1-2.5 m, 2.5-5 m, 5 or more m. In certain embodiments, the pore size is about 0.2 m. In certain embodiments, filtration or ultrafiltration includes size exclusion ranging from 100-500 daltons (Da), 500-1 kDa, 1-2 kDa, 2-5 kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa, 50-100 kDa, 100-250 kDa, 250-500 kDa, 500 or more kDa. In certain embodiments, the size exclusion is for about 2-5 kDa. In certain embodiments, the size exclusion is for about 3 kDa. In other embodiments, filtration or ultrafiltration includes size exclusion includes use of hollow fiber membranes capable of isolating particles ranging from 100-500 daltons (Da), 500-1 kDa, 1-2 kDa, 2-5 kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa, 50-100 kDa, 100-250 kDa, 250-500 kDa, 500 or more kDa. In certain embodiments, the size exclusion is for about 2-5 kDa. In certain embodiments, the size exclusion is for about 3 kDa. In other embodiments, a molecular weight cut-off (MWCO) gel filtration capable of isolating particles ranging from 100-500 daltons (Da), 500-1 kDa, 1-2 kDa, 2-5 kDa, 5-10 kDa, 10-25 kDa, 25-50 kDa, 50-100 kDa, 100-250 kDa, 250-500 kDa, 500 or more kDa. In certain embodiments, the size exclusion is for about 2-5 kDa. In certain embodiments, the size exclusion is for about 3 kDa. In various embodiments, such systems are used in combination with variable fluid flow systems. In certain embodiments, a size exclusion membrane with different pore sizes is used to purify extracellular vesicles from a solution comprising undesirable proteins or nucleic acids.
[0174] In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of tangential flow filtration (TFF) systems are used purify and/or concentrate the exosome fractions. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of liquid chromatography can also be used to purify artificial synapses to homogeneously sized particles. In various embodiments, density gradients as used, such as centrifugation in a sucrose density gradient or application of a discrete sugar cushion in preparation.
[0175] In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of a precipitation reagent. For example, a precipitation reagent, ExoQuick, can be added to conditioned cell media to quickly and rapidly precipitate a population of artificial synapses. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of volume-excluding polymers (e.g., polyethylene glycols (PEGs)) are used. In another embodiment, isolating a plurality of artificial synapses from the population of cells includes use of flow field-flow fractionation (FlFFF), an elution-based technique.
[0176] In certain embodiments, isolating a plurality of artificial synapses from the population of cells includes use of one or more capture agents to isolate one or more artificial synapses possessing specific biomarkers or containing particular biological molecules. In one embodiment, one or more capture agents include at least one antibody. For example, antibody immunoaffinity recognizing exosome-associated antigens is used to capture specific artificial synapses. In other embodiments, the at least one antibody are conjugated to a fixed surface, such as magnetic beads, chromatography matrices, plates or microfluidic devices, thereby allowing isolation of the specific exosome populations of interest. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of one or more capture agents that is not an antibody. This includes, for example, use of a bait molecule presenting an antigenic feature complementary to a corresponding molecule of interest on the exosome surface, such as a receptor or other coupling molecule. In one embodiment, the non-antibody capture agent is a lectin capable of binding to polysaccharide residues on the exosome surface.
[0177] In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of ion exchange chromatography. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of anion exchange chromatography. In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of caion exchange chromatography. In certain embodiments, ion exchange chromatography comprises a chromatography resin with a functional group selected from the group consisting of diethylaminoethyl (DEAE), quaternary aminoethyl (QAE), quaternary ammonium (Q), carboxymethyl (CM), sulfopropyl (SP), or methyl sulfate (S). In certain embodiments, ion exchange chromatography comprises a chromatography resin which may have properties of a weak acid, strong acid, weak base, or strong basic. In certain embodiments, ion exchange chromatography comprises a chromatography selected from the group consisting of DEAE cellulose, DEAE Sephadex, Mono Q, Mini Q, HiTrap Capto, Capto Core 700, HiPrep Q, QAE Sephadex, Q Sepharose, CM Cellulose, SP Sepharose, SOURCE S, EAH-Sepharose, sulfoxyethyl cellulose, CM Sephadex, or CM Sepharose. Isolating a plurality of artificial synapses can be prepared by any of a variety of ion exchange chromatography techniques that are known in the art.
[0178] In other embodiments, isolating a plurality of artificial synapses from the population of cells includes use of a nuclease enzyme (e.g., a DNase or RNase). For example, a working concentration of Benzonase nuclease may be added to an extracellular vesicle sample preparation in the presence of a divalent cation, for example 1-2 mM Mg2.sup.+, 2-5 mM Mg2.sup.+, 10-20 mM Mg2.sup.+, 20-50 mM Mg2.sup.+, 50-100 mM Mg2.sup.+, or more than 100 mM Mg2.sup.+.
[0179] Following isolation and purification of the engineered EVs provided herein, EVs can be further evaluated for the desired structural and functional properties by methods known in the art. For example, the engineered exosomes provided herein can be assayed for functional activity on a target cell using a cell-based bioassays (e.g., those commercially available, Promega DiscoverX), ligand-receptor binding assays, vesicle flow cytometric assays, enzyme-linked immunosorbent assays, tunable resistive pulse sensing (TRPS), nanoparticle tracking analysis (NTA), surface plasmon resonance (SSPR), nucleotide sequencing, lipidomics, proteomics, colorimetric assays, fluorescence assays, luminescence assays, immunoblotting, radioimmunoassays, electron microscopy, or EV automated analysis (e.g., Exoview). Additional methods of characterizing EVs are found, e.g., in Zhang Y, Bi J, Huang J, Tang Y, Du S, Li P. Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications. Int J Nanomedicine. 2020 Sep. 22; 15:6917-6934. doi: 10.2147/IJN.S264498. PMID: 33061359; PMCID: PMC7519827, Kluszczyska K, Czernek L, Cypryk W, Pezek , Dchler M. Methods for the Determination of the Purity of Exosomes. Curr Pharm Des. 2019; 25(42):4464-4485. doi: 10.2174/1381612825666191206162712. PMID: 31808383, Nolan J P, Duggan E. Analysis of Individual Extracellular Vesicles by Flow Cytometry. Methods Mol Biol. 2018; 1678:79-92. doi: 10.1007/978-1-4939-7346-0_5. PMID: 29071676.; Doyle L M, Wang M Z. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells. 2019 Jul. 15; 8(7):727. doi: 10.3390/cells8070727. PMID: 31311206; PMCID: PMC6678302, Pugholm L H, Revenfeld A L, Sndergaard EK, Jrgensen MM. Antibody-Based Assays for Phenotyping of Extracellular Vesicles. Biomed Res Int. 2015; 2015:524817. doi: 10.1155/2015/524817. Epub 2015 Dec. 3. PMID: 26770974; PMCID: PMC4681819, Shao H, Im H, Castro C M, Breakefield X, Weissleder R, Lee H. New Technologies for Analysis of Extracellular Vesicles. Chem Rev. 2018 Feb. 28; 118(4):1917-1950. doi: 10.1021/acs.chemrev.7b00534. Epub 2018 Jan. 31. PMID: 29384376; PMCID: PMC6029891, which are incorporated herein by reference in their entireties.
Pharmaceutical Compositions
[0180] Provided herein are compositions comprising the engineered extracellular vesicles (artificial synapses) provided herein.
[0181] In one aspect, provided herein is a composition comprising: a plurality of the engineered extracellular vesicles provided herein. In some embodiments of any of the aspects, the compositions and engineered EVs provided herein further comprise a pharmaceutically acceptable carrier.
[0182] For clinical use of the methods and compositions described herein, administration of the engineered EVs/artificial synapses provided herein can include formulation into pharmaceutical compositions or pharmaceutical formulations for parenteral administration, e.g., intravenous; mucosal, e.g., intranasal; ocular, or other mode of administration. In some embodiments, the engineered EVs described herein can be administered along with any pharmaceutically acceptable carrier compound, material, or composition which results in an effective treatment in the subject. Thus, a pharmaceutical formulation for use in the methods described herein can contain the engineered EVs described herein in combination with one or more pharmaceutically acceptable ingredients. The phrase pharmaceutically acceptable refers to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio. The phrase pharmaceutically acceptable carrier as used herein means a pharmaceutically acceptable material, composition or vehicle, such as a liquid or solid filler, diluent, excipient, solvent, media, encapsulating material, manufacturing aid (e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid), or solvent encapsulating material, involved in maintaining the stability, solubility, or activity of, an engineered EV as described herein. Each carrier must be acceptable in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. The terms excipient, carrier, pharmaceutically acceptable carrier or the like are used interchangeably herein.
[0183] The engineered EVs provided herein can be formulated for administration of the compound to a subject in solid, liquid, or gel form, including those adapted for the following: (1) parenteral administration, for example, by subcutaneous, intramuscular, intravenous or epidural injection as, for example, a sterile solution or suspension, or sustained-release formulation; (2) transdermally; (3) transmucosally; (4) via bronchoalveolar lavage.
[0184] In some embodiments, the compositions described herein comprise a particle or polymer-based vehicle. Exemplary particle or polymer-based vehicles include, but are not limited to, nanoparticles, microparticles, polymer microspheres, or polymer-drug conjugates.
[0185] In one embodiment of any of the aspects, the compositions described herein further comprise a lipid vehicle. Exemplary lipid vehicles include, but are not limited to, liposomes, phospholipids, micelles, lipid emulsions, and lipid-drug complexes.
[0186] Formulations can be adapted for delivery to the airway, e.g., to address respiratory infection. Such formulations can be adapted for delivery as an aerosol, e.g., for inhalation. In some embodiments, the compositions described herein are formulated for aerosol administration, nebulizer administration, tracheal lavage administration, or for a pulmonary delivery device.
[0187] As used herein, the term pulmonary delivery device refers to a device used to deliver a therapeutic dose of a composition of the present invention to the respiratory system including, but not limited to, a nebulizer, metered-dose inhaler, or dry powder inhaler.
[0188] Examples of nebulizers include, but are not limited to, soft mist inhalers (for example Respimat Boehringer Ingelheim) jet nebulizers (use compressed gas or air), ultrasonic nebulizers (produce aerosols using a piezoelectric crystal vibrating at high frequencies), and vibrating mesh nebulizers.
[0189] As used herein, the term jet nebulizer refers to a device that flows compressed air or gas through a composition of the present invention for aerosolization. The aerosolized composition of the present invention may be inhaled by a patient. Jet nebulizer may include, but is not limited to, jet nebulizers with a corrugated tube, jet nebulizers with a collection bag, breath enhanced jet nebulizers, breath actuated jet nebulizers, and metered-dose inhalers. Examples of jet nebulizers include, but are not limited to, Circulaire (Westmed INC, Tucson, AZ), Pari Inhalierboy (PARI, Midlothian, VA), Pari LC Plus (PARI, Midlothian, VA), NebuTech (Salter Labs, Arvin, CA), AeroEclipse (Monoghan/Trudell Medical International, London, Ontario, Canada), and Maxin MA-2 (MA-2; Clinova Medical AB, Malmo, Sweden). Examples of ultrasonic nebulizers include, but are not limited to, DeVilbiss-Pulmosonic (Somerset, PA), Omron-Microair (Omron, Kyoto, Japan), Omron NE-U17 (Omron, Kyoto, Japan), Rhone Poulenc-Rorer-Fisoneb (Sanofi, Paris, France), and Beurer Nebulizer IH30 (Beurer GmbH, Neu-Ulm, Germany).
[0190] As used herein, the term mesh nebulizer refers to forcing a liquid, gel, fluid, solution, tincture, or the like through apertures in a mesh or aperture plate to generate aerosol. Mesh nebulizer may include, but is not limited to, active mesh nebulizers and passive mesh nebulizers. Examples of active mesh nebulizers include, but is not limited to, Aeroneb (Aerogen, Galway, Ireland) and eFlow (PARI, Midlothian, VA). Examples of passive mesh nebulizers are, but not limited to, I-neb (Philips Respironics, Newark, USA), AKITA (Activaero, Gemunden/Wohra, Germany), and Microair NE-U22 (Omron, Kyoto, Japan).
[0191] For use as aerosols, the compositions described herein can be prepared in a solution or suspension and may be packaged in a pressurized aerosol container together with suitable propellants, for example, hydrocarbon propellants like propane, butane, or isobutane with conventional excipients.
[0192] The engineered EVs provided herein can also be administered in a non-pressurized form such as in a nebulizer or atomizer that reduces a liquid to a fine spray. Preferably, by such nebulization small liquid droplets of uniform size are produced from a larger body of liquid in a controlled manner. Nebulization can be achieved by any suitable means therefor, including by using many nebulizers known and marketed today. For example, an AEROMIST pneumatic nebulizer available from Inhalation Plastic, Inc. of Niles, Ill.
[0193] When the active ingredients are adapted to be administered, either together or individually, via nebulizer(s) they can be in the form of a nebulized aqueous suspension or solution, with or without a suitable pH or tonicity adjustment, either as a unit dose or multi-dose device.
[0194] Furthermore, any suitable gas can be used to apply pressure during the nebulization, with preferred gases to date being those which are chemically inert. Exemplary gases including, but are not limited to, nitrogen, argon, or helium can be used to advantage.
[0195] In some embodiments, the compositions described herein can also be administered directly to the airways in the form of a dry powder. Thus, the engineered EVs can be administered via an inhaler. Exemplary inhalers include metered dose inhalers and dry powdered inhalers.
[0196] A metered dose inhaler or MDI is a pressure resistant canister or container filled with a product such as a pharmaceutical composition dissolved in a liquefied propellant or micronized particles suspended in a liquefied propellant. The propellants which can be used include chlorofluorocarbons, hydrocarbons or hydrofluoroalkanes. Commonly used propellants are P134a (tetrafluoroethane) and P227 (heptafluoropropane) each of which may be used alone or in combination. They are optionally used in combination with one or more other propellants and/or one or more surfactants and/or one or more other excipients, for example ethanol, a lubricant, an anti-oxidant and/or a stabilizing agent.
[0197] As used herein, the term dry powder inhaler refers to a device that delivers a therapeutic dose of a composition of the present invention in a powdered form without propellants to the respiratory system. A dry powder inhaler (i.e., Turbuhaler (Astra AB)) is a system operable with a source of pressurized air to produce dry powder particles of a pharmaceutical composition that is compacted into a very small volume. Examples of dry powder inhalers include, but are not limited to, Spinhaler (Fisons Pharmaceuticals, Rochester, NY), Rotahaler (GlaxoSmithKline, NC), Turbuhaler (AstraZeneca, UK), and Diskhaler (GlaxoSmithKline, NC).
[0198] Dry powder aerosols for inhalation therapy are generally produced with mean diameters primarily in the range of <5 m. As the diameter of particles exceeds 3 m, there is increasingly less phagocytosis by macrophages. However, increasing the particle size also has been found to minimize the probability of particles (possessing standard mass density) entering the airways and acini due to excessive deposition in the oropharyngeal or nasal regions.
[0199] Suitable powder compositions include, by way of illustration, powdered preparations including the engineered EVs described herein. These can be intermixed with lactose, or other inert powders acceptable for intrabronchial administration. The powder compositions can be administered via an aerosol dispenser or encased in a breakable capsule which may be inserted by the patient or clinician into a device that punctures the capsule and blows the powder out in a steady stream suitable for inhalation. The compositions can include propellants, surfactants, and co-solvents and may be filled into conventional aerosol containers that are closed by a suitable metering valve.
[0200] Aerosols for the delivery to the respiratory tract are described, for example, by Adjei, A. and Garren, J. Pharm. Res., 1: 565-569 (1990); Zanen, P. and Lamm, J.-W. J. Int. J. Pharm., 114: 111-115 (1995); Gonda, I. Aerosols for delivery of therapeutic and diagnostic agents to the respiratory tract, in Critical Reviews in Therapeutic Drug Carrier Systems, 6:273-313 (1990); Anderson et al., Am. Rev. Respir. Dis., 140: 1317-1324 (1989)) and have potential for the systemic delivery of peptides and proteins as well (Patton and Platz, Advanced Drug Delivery Reviews, 8:179-196 (1992)); Timsina et. al., Int. J. Pharm., 101: 1-13 (1995); and Tansey, I. P., Spray Technol. Market, 4:26-29 (1994); French, D. L., Edwards, D. A. and Niven, R. W., Aerosol Sci., 27: 769-783 (1996); Visser, J., Powder Technology 58: 1-10 (1989)); Rudt, S. and R. H. Muller, J. Controlled Release, 22: 263-272 (1992); Tabata, Y, and Y. Ikada, Biomed. Mater. Res., 22: 837-858 (1988); Wall, D. A., Drug Delivery, 2: 10 1-20 1995); Patton, J. and Platz, R., Adv. Drug Del. Rev., 8: 179-196 (1992); Bryon, P., Adv. Drug. Del. Rev., 5: 107-132 (1990); Patton, J. S., et al., Controlled Release, 28: 15 79-85 (1994); Damms, B. and Bains, W., Nature Biotechnology (1996); Niven, R. W., et al., Pharm. Res., 12(9); 1343-1349 (1995); and Kobayashi, S., et al., Pharm. Res., 13(1): 80-83 (1996), the contents of each of which are incorporated herein by reference in their entirety.
[0201] Microemulsification technology can improve bioavailability of some lipophilic (water insoluble) pharmaceutical agents. Examples include Trimetrine (Dordunoo, S. K., et al., Drug Development and Industrial Pharmacy, 17(12), 1685-1713, 1991 and REV 5901 (Sheen, P. C., et al., J Pharm Sci 80(7), 712-714, 1991). Among other things, microemulsification provides enhanced bioavailability by preferentially directing absorption to the lymphatic system instead of the circulatory system, which thereby bypasses the liver, and prevents destruction of the cell-based compositions in the hepatobiliary circulation.
[0202] The engineered EVs described herein can be formulated with an amphiphilic carrier. Amphiphilic carriers are saturated and monounsaturated polyethyleneglycolyzed fatty acid glycerides, such as those obtained from fully or partially hydrogenated various vegetable oils. Such oils may advantageously consist of tri-, di-, and mono-fatty acid glycerides and di- and mono-polyethyleneglycol esters of the corresponding fatty acids, with a particularly preferred fatty acid composition including capric acid 4-10, capric acid 3-9, lauric acid 40-50, myristic acid 14-24, palmitic acid 4-14 and stearic acid 5-15%. Another useful class of amphiphilic carriers includes partially esterified sorbitan and/or sorbitol, with saturated or mono-unsaturated fatty acids (SPAN-series) or corresponding ethoxylated analogs (TWEEN-series).
[0203] Commercially available amphiphilic carriers are particularly contemplated, including Gelucire-series, Labrafil, Labrasol, or Lauroglycol (all manufactured and distributed by Gattefosse Corporation, Saint Priest, France), PEG-mono-oleate, PEG-di-oleate, PEG-mono-laurate and di-laurate, Lecithin, Polysorbate 80, etc. (produced and distributed by a number of companies in USA and worldwide).
[0204] The engineered EV compositions provided herein can be formulated with hydrophilic polymers. Hydrophilic polymers are water-soluble, can be covalently attached to a vesicle-forming lipid, and which are tolerated in vivo without toxic effects (i.e., are biocompatible). Suitable polymers include polyethylene glycol (PEG), polylactic (also termed polylactide), polyglycolic acid (also termed polyglycolide), a polylactic-polyglycolic acid copolymer, and polyvinyl alcohol. Other hydrophilic polymers which may be suitable include polyvinylpyrrolidone, polymethoxazoline, polyethyloxazoline, polyhydroxypropyl methacrylamide, polymethacrylamide, polydimethylacrylamide, and derivatized celluloses such as hydroxymethylcellulose or hydroxyethylcellulose.
[0205] In certain embodiments, a pharmaceutical composition as described herein comprises a biocompatible polymer selected from the group consisting of polyamides, polycarbonates, polyalkylenes, polymers of acrylic and methacrylic esters, polyvinyl polymers, polyglycolides, polysiloxanes, polyurethanes and co-polymers thereof, celluloses, polypropylene, polyethylenes, polystyrene, polymers of lactic acid and glycolic acid, polyanhydrides, poly(ortho)esters, poly(butic acid), poly(valeric acid), poly(lactide-co-caprolactone), polysaccharides, proteins, polyhyaluronic acids, polycyanoacrylates, and blends, mixtures, or copolymers thereof.
[0206] In certain embodiments, a pharmaceutical composition described herein is formulated as a liposome. Liposomes can be prepared by any of a variety of techniques that are known in the art. See, e.g., U.S. Pat. No. 4,235,871; Published PCT applications WO 96/14057; New RRC, Liposomes: A practical approach, IRL Press, Oxford (1990), pages 33-104; Lasic D D, Liposomes from physics to applications, Elsevier Science Publishers BV, Amsterdam, 1993.
[0207] Therapeutic formulations of the engineered EV compositions as described herein can be prepared for storage by with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN, PLURONICS or polyethylene glycol (PEG).
[0208] Vaccine or other pharmaceutical compositions comprising an engineered EV composition as described herein can contain a pharmaceutically acceptable salt, typically, e.g., sodium chloride, and preferably at about physiological concentrations. The formulations of the vaccine or other pharmaceutical compositions described herein can contain a pharmaceutically acceptable preservative. In some embodiments, the preservative concentration ranges from 0.1 to 2.0%, typically v/v. Suitable preservatives include those known in the pharmaceutical arts. Benzyl alcohol, phenol, m-cresol, methylparaben, and propylparaben are examples of preservatives. The formulations of the vaccine or other pharmaceutical compositions described herein can include a pharmaceutically acceptable surfactant at a concentration of 0.005 to 0.02%.
[0209] Therapeutic pharmaceutical compositions described herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
[0210] In some embodiments in which the engineered EVs are formulated for use in or with a vaccine, the vaccine composition can be formulated with the engineered EVs as an adjuvant. In other embodiments the vaccine composition can be formulated with the engineered EVs and an additional adjuvant, e.g., as known in the art.
[0211] As used herein in the context of immunization, immune response and vaccination, the term adjuvant refers to any substance than when used in combination with a specific antigen produces a more robust immune response than the antigen alone. When incorporated into a vaccine formulation, an adjuvant acts generally to accelerate, prolong, or enhance the quality of specific immune responses to the vaccine antigen(s). Adjuvants typically promote the accumulation and/or activation of accessory cells or factors to enhance antigen-specific immune responses and thereby enhance the efficacy of vaccines, i.e., antigen-containing or encoding compositions used to induce protective immunity against the antigen.
[0212] Adjuvants, in general, include adjuvants that create a depot effect, immune-stimulating adjuvants, and adjuvants that create a depot effect and stimulate the immune system. An adjuvant that creates a depot effect is an adjuvant that causes the antigen to be slowly released in the body, thus prolonging the exposure of immune cells to the antigen. This class of adjuvants includes but is not limited to alum (e.g., aluminum hydroxide, aluminum phosphate); emulsion-based formulations including mineral oil, non-mineral oil, water-in-oil or oil-in-water-in oil emulsion, oil-in-water emulsions such as Seppic ISA series of Montanide adjuvants (e.g., Montanide ISA 720; AirLiquide, Paris, France); MF-59 (a squalene-in-water emulsion stabilized with Span 85 and Tween 80; Chiron Corporation, Emeryville, Calif.); and PROVAX (an oil-in-water emulsion containing a stabilizing detergent and a micelle-forming agent; IDEC Pharmaceuticals Corporation, San Diego, Calif).
[0213] An immune-stimulating adjuvant is an adjuvant that causes activation of a cell of the immune system. It may, for instance, cause an immune cell to produce and secrete cytokines and interferons. This class of adjuvants includes but is not limited to saponins purified from the bark of the Q. saponaria tree, such as QS21 (a glycolipid that elutes in the 21st peak with HPLC fractionation; Aquila Biopharmaceuticals, Inc., Worcester, Mass.); poly[di(carboxylatophenoxy)phosphazene (PCPP polymer; Virus Research Institute, USA); derivatives of lipopolysaccharides such as monophosphoryl lipid A (MPL; Ribi ImmunoChem Research, Inc., Hamilton, Mont.), muramyl dipeptide (MDP; Ribi) and threonyl-muramyl dipeptide (t-MDP; Ribi); OM-174 (a glucosamine disaccharide related to lipid A; OM Pharma SA, Meyrin, Switzerland); and Leishmania elongation factor (a purified Leishmania protein; Corixa Corporation, Seattle, Wash.). This class of adjuvants also includes CpG DNA.
[0214] Adjuvants that create a depot effect and stimulate the immune system are those compounds which have both of the above-identified functions. This class of adjuvants includes but is not limited to ISCOMS (immunostimulating complexes which contain mixed saponins, lipids and form virus-sized particles with pores that can hold antigen; CSL, Melbourne, Australia); SB-AS2 (SmithKline Beecham adjuvant system #2 which is an oil-in-water emulsion containing MPL and QS21: SmithKline Beecham Biologicals [SBB], Rixensart, Belgium); SB-AS4 (SmithKline Beecham adjuvant system #4 which contains alum and MPL; SBB, Belgium); non-ionic block copolymers that form micelles such as CRL 1005 (these contain a linear chain of hydrophobic polyoxypropylene flanked by chains of polyoxyethylene; Vaxcel, Inc., Norcross, Ga.); and Syntex Adjuvant Formulation (SAF, an oil-in-water emulsion containing Tween 80 and a nonionic block copolymer; Syntex Chemicals, Inc., Boulder, Colo.).
[0215] The active ingredients of the pharmaceutical compositions described herein can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).
[0216] In some embodiments, sustained-release preparations can be used. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing a composition described herein in which the matrices are in the form of shaped articles, e.g., films, or microcapsule. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and y ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-()-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. When encapsulated, the composition can remain in the body for a long time (e.g., up to about 1 hour, between 1-12 hours, 12-24 hours, 24 hours to 2 days, 2-3 days, 3-4 days, 4-5 days, 5-6 days, 6-7 days, 1-2 weeks, 3-4 weeks, 4 weeks to 2 months, 2-3 months, 3-4 months, 4-5 months, 5-6 months, or more than 6 months, or a variation thereof), denature, or aggregate as a result of exposure to moisture at 37 C., resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular SS bond formation through thio-disulfide interchange, stabilization can be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions.
Administration, Dosing, Efficacy
[0217] The engineered EV compositions, pharmaceutical compositions, or vaccine compositions described herein can be formulated, dosed, and administered in a fashion consistent with good medical practice. Factors for consideration in this context include the particular disorder being treated, the particular subject being treated, the clinical condition of the individual subject, the cause of the disorder, the site of delivery of the vaccine composition, the method of administration, the scheduling of administration, and other factors known to medical practitioners.
[0218] Generally, application of artificial synapses as therapy will take into account similar parameters as other therapeutic strategies, including concentration, timing of delivery, and sustained bioavailability at injury/disease site. Extracellular vesicle can be delivered via a number of routes: intravenous, intracoronary, and intramyocardial. Extracellular vesicles (e.g., exosomes), also allow for new delivery routes that were previously infeasible for cell therapy, such as inhalation or injection. These various approaches are described below, including injection, topical application, enteral administration, and pulmonary delivery.
[0219] The engineered EV compositions provided herein can be administered to a subject in need thereof by any appropriate route which results in an effective treatment in the subject. As used herein, the terms administering, and introducing are used interchangeably and refer to the placement of a composition provided herein into a subject by a method or route which results in at least partial localization of such compositions at a desired site, such as a site of inflammation or a tumor, such that a desired effect(s) is produced. The compositions can be administered to a subject by any mode of administration that delivers the composition systemically or to a desired surface or target, and can include, but is not limited to, injection, infusion, instillation, and inhalation administration. To the extent that the composition can be protected from inactivation in the gut, oral administration forms are also contemplated. Injection includes, without limitation, intravenous, intramuscular, intra-arterial, intrathecal, intraventricular, intracapsular, intraorbital, retro-orbital, intravitreal, intraocular, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, sub capsular, subarachnoid, intraspinal, intracerebral, intratarsal, and intrasternal, intratumoral injection, and infusion or the like as known in the art.
[0220] A therapeutic does of the present invention may be delivered to a patient by means of controlled release, for example but not limited to, implantable pump and implantable cannulas to provide continuous access to the venous or arterial system.
[0221] Topical application refers to applying or spreading a composition of the present invention onto surfaces on or in the body, both internally and/or externally, in a therapeutically effective amount for local and/or systemic treatment. Topical application may be epicutaneous wherein a composition of the present invention may be directly applied onto a localized surface of the skin or mucous membranes. Topical application may include transdermal application wherein a composition of the present invention may be absorbed into the body to obtain systemic delivery and systemic distribution. Topical application formulations may include, but are not limited to, creams, foams, gels, lotions, solutions, ointments, dermal patch, transdermal patches, powder, solid, sponge, tape, vapor, paste, film, liposomes, balm, shampoo, spray, or tincture or the like or a combination thereof. A therapeutic dose of a composition of the present invention may be delivered vaginally (for example a vaginal suppository, vaginal ring, douche, intrauterine device, intravesical infusion, and the like) or urethra or the like or a combination thereof.
[0222] Enteral administration refers to a composition of the present invention administered via the gastrointestinal tract in a therapeutically effective amount for local or systemic treatment. Enteral administration may include, but is not limited to, delivery of a composition of the present invention via the mouth, sublingual, esophagus, gastric (for example the stomach), small intestines, large intestines or rectum. Oral delivery of the present invention may include, but is not limited to, the use of a capsule, pastille, pill, tablet, solution, gel, suspension, emulsion, syrup, elixir, tincture, mouthwash, lozenges, chewing gum, lollipop, cream, foam, solution, powder, solid, vapor, liposomes, spray, or tincture osmotic-controlled release oral delivery system, or the like. Gastric delivery may involve the use of a tube or nasal passage that leads directly to the stomach, for example, a percutaneous endoscopic gastrostomy tube. Gastric delivery may involve direct injection made through the abdominal wall. Rectal delivery may involve, but is not limited to, the use of a suppository, ointment, enema, murphy drip, or the like. A therapeutic does of the present invention may be delivered to a patient by means of controlled release, for example but not limited to, controlled release drug delivery pellet or pill.
[0223] Inhalation (i.e., pulmonary delivery, pulmonary administration refers to delivery to the respiratory system through the respiratory route, including but not limited to, intranasal administration, oral administration, and oral inhalative administration (e.g., intratracheal instillation and intratracheal inhalation) of a therapeutically effective amount for local or systemic treatment. Pulmonary delivery of a therapeutically effective amount of a composition of the present invention may be achieved by dispersion, for example by using a syringe. Pulmonary delivery of a composition of the present invention may be achieved by aerosol administration, wherein aerosol administration may deposit a therapeutically effective amount of the present invention by gravitational sedimentation, inertial impaction, or diffusion.
[0224] Intravenous delivery technique can occur through a peripheral or central venous catheter. As the simplest delivery mode, this technique avoids the risk of an invasive procedure. However, intravenous may be regarded as a comparatively inefficient and less localized delivery method, as a high percentage of infused cell exosomes may become sequestered in organs such as the lung, liver, or spleen. Such sequestration may result in few or no cellular exosomes reaching broader circulation or have unintended systemic effects following their distribution.
[0225] In certain embodiments, administration can include delivery to a tissue or organ site that is the same as the site of diseased and/or dysfunctional tissue. In certain embodiments, administration can include delivery to a tissue or organ site that is different from the site or diseased and/or dysfunctional tissue. In certain embodiments, the delivery is via inhalation or oral administration. In various embodiments, administration of artificial synapses can include combinations of multiple delivery techniques.
[0226] In some embodiments, the compositions described herein are administered by aerosol administration, nebulizer administration, or tracheal lavage administration.
[0227] The term effective amount as used herein refers to the amount of an engineered EV composition needed to alleviate or prevent at least one or more symptom of a disease or disorder (e.g., autoimmune disease or cancer), and relates to a sufficient amount of pharmacological composition to provide the desired effect, e.g., reduce the pathology, or any symptom associated with or caused by the disease. The term therapeutically effective amount therefore refers to an amount of an engineered EV composition or vaccine composition described herein using the methods as disclosed herein, that is sufficient to affect a particular disease state when administered to a typical subject. An effective amount as used herein would also include an amount sufficient to delay the development of a symptom of the disease, alter the course of a symptom disease (for example, but not limited to, slow the progression of a symptom of the disease), or reverse a symptom of the disease. Thus, it is not possible to specify the exact effective amount. However, for any given case, an appropriate effective amount can be determined by one of ordinary skill in the art using only routine experimentation.
[0228] Effective amounts, toxicity, and therapeutic efficacy can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dosage can vary depending upon the dosage form employed and the route of administration utilized. The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio LD50/ED50. Compositions and methods that exhibit large therapeutic indices are preferred. A therapeutically effective dose can be estimated initially from cell culture assays. Also, a dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the engineered EVs or fusion polypeptides provided herein), which achieves a half-maximal inhibition of symptoms) as determined in cell culture, or in an appropriate animal model. Levels of therapeutic engineered EVs in plasma can be measured, for example, by high performance liquid chromatography, enzyme linked immunosorbent assay (ELISA), flow cytometry, FACS sorting, western blot, mass spectroscopy, tunable resistive pulse sensing, ExoView, qRT-PCR, next generation sequencing (NGS), or by any analysis technique known by one of ordinary skill in the art. The effects of any particular dosage can be monitored by a suitable bioassay. The dosage can be determined by a physician and adjusted, as necessary, to suit observed effects of the treatment.
[0229] The engineered EV compositions, pharmaceutical compositions, or vaccine compositions described herein can be formulated, in some embodiments, with one or more additional therapeutic agents currently used to prevent or treat the infection, for example. The effective amount of such other agents depends on the amount of an engineered EV in the formulation, the type of disorder or treatment, and other factors discussed above. These are generally used in the same dosages and with administration routes as used herein before or about from 1 to 99% of the heretofore employed dosages.
[0230] The dosage ranges for the pharmaceutical compositions described herein depend upon the potency and encompass amounts large enough to produce the desired effect. The dosage should not be so large as to cause unacceptable adverse side effects. Generally, the dosage will vary with the age, condition, health, and sex of the patient and can be determined by one of skill in the art. The dosage can also be adjusted by the individual physician in the event of any complication. In some embodiments, the dosage ranges from 0.001 mg/kg body weight to 100 mg/kg body weight. In some embodiments, the dose range is from 5 g/kg body weight to 100 g/kg body weight. Alternatively, the dose range can be titrated to maintain serum levels between 0.1 g/mL and 1000 g/mL. For systemic administration, subjects can be administered a therapeutic amount, such as, e.g., 0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, 5 mg/kg, 7.5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 40 mg/kg, 50 mg/kg, or more. These doses can be administered by one or more separate administrations, or by continuous infusion. For repeated administrations over several days or longer, depending on the condition, the treatment is sustained until, for example, the infection is treated, as measured by the methods described above or known in the art. However, other dosage regimens can be useful.
[0231] In various embodiments, the quantities of artificial synapses that are administered to achieve these effects range from 110.sup.6 to 110.sup.7, 110.sup.7 to 110.sup.8, 110.sup.8 to 110.sup.10, 110.sup.10 to 110.sup.10, 110.sup.10 to 110.sup.11, 110.sup.11 to 110.sup.12, 110.sup.12 to 110.sup.13, 110.sup.13 to 110.sup.14, 110.sup.14 to 110.sup.15, 110.sup.15 or more EVs/artificial synapses. In other embodiments, the numbers of artificial synapses are relative to the number of cells used in a clinically relevant dose for a cell-therapy method. For example, defining an effective dose range, dosing regimen and route of administration, may be guided by studies using fluorescently labeled artificial synapses, and measuring target tissue retention, which can be >10, >50, or >100 background, as measured 5, 10, 15, 30, or 30 or more min as a screening criterion. In certain embodiments, >100 background measured at 30 mins is a baseline measurement for a low and high dose that is then assess for safety and bioactivity (e.g., using MRI endpoints: scar size, global and regional function of the target organ being treated). In various embodiments, single doses are compared to two, three, four, four or more sequentially-applied doses. In various embodiments, the repeated or sequentially-applied doses are provided for treatment of an acute disease and/or condition. In various embodiments, the repeated or sequentially-applied doses are provided for treatment of a chronic disease and/or condition. In other embodiments, administration of the plurality of artificial synapses is adjunctive to standard therapy.
[0232] In other embodiments, administering a composition includes 110.sup.10 or more artificial synapses in a single dose. In various embodiments, exosome quantity may be defined by protein quantity, such as dosages including 1-10, 10-25, 25-50, 50-75, 75-100, or 100 or more mg exosome protein. In other embodiments, a single dose is administered multiple times to the subject. In other embodiments, administering a composition consists of one or more of: injection, topical administration, enteral, intravenous, intra-arterial, or inhalation.
[0233] In various embodiments, exosome quantity may be defined by protein quantity, such as dosages including 1-10, 10-25, 25-50, 50-75, 75-100, or 100 or more mg exosome protein. In various embodiments, administering a composition includes multiple dosages of the artificial synapses. In various embodiments, the repeated or sequentially-applied doses are provided for treatment of an acute disease and/or condition. In various embodiments, the repeated or sequentially-applied doses are provided for treatment of a chronic disease and/or condition.
[0234] In other embodiments, administering a composition including a plurality of artificial synapses to the subject is adjunctive to standard therapy.
[0235] The duration of a therapy using the methods described herein will continue for as long as medically indicated or until a desired therapeutic effect (e.g., those described herein) is achieved. In certain embodiments, the administration of the vaccine composition described herein is continued for 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 1 year, 2 years, 3 years, 4 years, 5 years, 10 years, 20 years, or for a period of years up to the lifetime of the subject.
[0236] As will be appreciated by one of skill in the art, appropriate dosing regimens for a given composition can comprise a single administration/immunization or multiple ones. Subsequent doses may be given repeatedly at time periods, for example, about two weeks or greater up through the entirety of a subject's life, e.g., to provide a sustained preventative effect. Subsequent doses can be spaced, for example, about two weeks, about three weeks, about four weeks, about one month, about two months, about three months, about four months, about five months, about six months, about seven months, about eight months, about nine months, about ten months, about eleven months, or about one year after a primary immunization.
[0237] The precise dose to be employed in the formulation will also depend on the route of administration and should be decided according to the judgment of the practitioner and each patient's circumstances. Ultimately, the practitioner or physician will decide the amount of the engineered EV or composition thereof to administer to particular subjects.
Methods of Modulating Inflammation and Treating Autoimmune Diseases
[0238] The artificial synapses/engineered EVs and compositions thereof provided herein can be deployed in a therapeutic strategy against virtually any injury/disease, as providing a platform for altering biological signaling. This includes, for example, inflammation and immune signaling, which plays a role in virtually all injuries and diseases in living organisms.
[0239] Thus, described herein is a method of modulating inflammation, including selecting a subject afflicted with an inflammatory related disease and/or condition; and administering to the subject a composition including a plurality of artificial synapses (engineered EVs) to the subject, wherein administration of the composition modulates inflammation.
[0240] As used herein, the term inflammation or inflamed refers to activation or recruitment of the immune system or immune cells (e.g., T cells, B cells, macrophages). A tissue that has inflammation can become reddened, white, swollen, hot, painful, sensitivity, exhibit a loss of function, or have a film or mucus. Methods of identifying inflammation are well known in the art. Inflammation typically occurs following injury, infection by a microorganism, exposure to a substance (e.g., a toxin, chemical, or dust) or autoimmune dysfunction. Onset of inflammation may be rapid (e.g., immediately following injury) or slow (e.g., repeated exposure to an irritant such as a chemical over time) with a duration of minutes, hours, days, months, years, or an individual's life.
[0241] Inflammation plays a vital role in alerting the immune system of potential danger and damage within a body. Inflammation is necessary to control and repair injury. For example, acute inflammation is a response to physical trauma, infection, and stress. Acute inflammation helps prevent further injury and triggers healing and recovery. Unfortunately, inflammation can become excessive and inappropriately active, lasting beyond the typical recovery time from an injury or infection. Wherein healthy inflammation helps a body respond to injury, chronic inflammation perpetuates injury and may lead to negative consequences to one's health. In particular, autoimmune diseases are chronic diseases from a host's immune system attacking itself, often due to aberrant biological signaling in the host. Restoring normal homeostatic signaling via application of artificial synapses, particularly targeting immune checkpoints, represents a highly promising avenue. For example, surface bound immune-checkpoint proteins or fragments thereof may modulate immune cell stimulation and affect suppression of immune cell function when delivered via artificial synapses. Injection, inhalation, ingestion or topical application of artificial synapses with surface bound immune-checkpoint proteins or fragments thereof may be used to treat immune, auto-immune, inflammatory, and auto-inflammatory conditions. Examples include chronic obstructive pulmonary disease (COPD) which is an inflammatory, progressive, life-threatening lung disease, psoriasis, a common chronic noncommunicable inflammatory skin disease, arthritis, a debilitating and painful degeneration of joints, among others well-understood to one of skill in the art.
[0242] In other embodiments, the inflammatory related disease and/or condition is acute, for example septicemia. In other embodiments, the inflammatory related disease and/or condition is chronic, for example chronic obstructive pulmonary disease. In other embodiments, the inflammatory condition is an autoimmune disease wherein the autoimmune disease and/or condition is one or more of polymyositis, dermatomyositis, Graves' disease, Hashimoto's thyroiditis, myasthenia gravis, vasculitis, multiple sclerosis, psoriasis, rheumatoid arthritis, psoriatic arthritis, scleroderma, systemic lupus erythematosus, inflammatory bowel disease, Crohn's disease, hyperthyroidism, autoimmune adrenal insufficiency, Sjogren syndrome, type I diabetes mellitus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, myasthenia gravis, ulcerative colitis, uveitis, polyarteritis nodosa, relapsing polychondritis, Behcet's disease, reactive arthritis, ankylosing spondylitis, Guillain-Barre syndrome, or optic neuropathy. In other embodiments, the disease and/or condition is chronic obstructive pulmonary disease, rheumatoid arthritis, uveoretinitis, psoriasis, and eczema. In other embodiments, the disease and/or condition is irritable bowel disease, multiple sclerosis or lupus
[0243] In other embodiments, the inflammatory related disease and/or condition is an ocular disease. As used herein, the terms ocular disease, eye disorder and eye disease are used interchangeably and refer to a disease or disorder that affects the health and/or vision of either one or both eyes or the general area of the eye(s), eye lid(s), or area surrounding or in near proximity to the eye(s). Eye disease may include, but are not limited to, macular degeneration (e.g., age-related macular degeneration), cataracts, diabetic retinopathy, diabetic macular edema, eye floaters, eye flashes, glaucoma, amblyopia, strabismus, retinitis (e.g., CMV retinitis), color blindness, keratoconus, retinal detachment, eyelid twitching, ocular hypertension, blepharitis, uveitis, Bietti's crystalline dystrophy, blepharospasm, cornea and corneal diseases, dry eye, histoplasmosis, macular hole, macular pucker, conjunctivitis, presbyopia, retinoblastoma, retinitis pigmentosa, retinopathy, Stargardt disease, Usher syndrome, uveal Coloma, and vitreous detachment, or the like.
[0244] Described herein is a method for treatment including, selecting a subject in need of treatment, administering a composition including a plurality of artificial synapses to the individual, wherein administration of the composition treats the subject. In certain embodiments, the subject is in need to treatment for a disease and/or condition involving tissue damage or dysfunction.
[0245] Described herein is a method of treating an autoimmune disease, inflammation, inflammatory disease or condition, or cancer in a subject, the method comprising: administering to a subject an engineered EV or composition thereof as provided herein to the subject.
[0246] Measured or measurable parameters include clinically detectable markers of disease, for example, elevated or depressed levels of a clinical or biological marker, as well as parameters related to a clinically accepted scale of symptoms or markers for a disease or disorder. It will be understood, however, that the total usage of the compositions and formulations as disclosed herein will be decided by the attending physician within the scope of sound medical judgment. The exact amount required will vary depending on factors such as the type of disease being treated.
[0247] Non-limiting examples of clinical tests that can be used to assess autoimmune diseases, inflammatory conditions, or inflammation parameters include blood tests, skin biopsy, MRI, eye examination, ocular pressure tests, etc. Where necessary or desired, animal models of injury or disease can be used to gauge the effectiveness of a particular composition as described herein. For example, an EAU animal model, as demonstrated in the working examples can be used.
[0248] In various embodiments, administration of the plurality of artificial synapses alters gene expression in the damaged or dysfunctional tissue, improves viability of the damaged tissue, and/or enhances regeneration or production of new tissue in the individual. In various embodiments, administration of the plurality of artificial synapses alters gene expression in the damaged or dysfunctional tissue, improves viability of the damaged tissue, and/or enhances regeneration or production of new tissue in the individual.
[0249] In various embodiments, the damaged or dysfunctional tissue is in need of repair, regeneration, or improved function due to an acute event. Acute events include, but are not limited to, trauma such as laceration, crush or impact injury, shock, loss of blood or oxygen flow, infection, chemical or heat exposure, poison or venom exposure, drug overuse or overexposure, and the like. Other sources of damage also include, but are not limited to, injury, age-related degeneration, cancer, and infection. In several embodiments, the regenerative cells used to prepare the engineered EVs provided herein are from the same tissue type as is in need of repair or regeneration. In several other embodiments, the regenerative cells are from a tissue type other than the tissue in need of repair or regeneration. In some embodiments, the engineered EVs provided herein are derived from the subject being treated. In some embodiments, the engineered EVs are derived from a donor subject.
[0250] In other embodiments, the damaged or dysfunctional tissue is in need of repair, regeneration, or improved function due to damage from chronic disease.
Some Selected Definitions
[0251] All references cited herein are incorporated by reference in their entirety as though fully set forth. Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Allen et al., Remington: The Science and Practice of Pharmacy 22.sup.nd ed., Pharmaceutical Press (Sep. 15, 2012); Hornyak et al., Introduction to Nanoscience and Nanotechnology, CRC Press (2008); Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology 3.sup.rd ed., revised ed., J. Wiley & Sons (New York, NY 2006); Smith, March's Advanced Organic Chemistry Reactions, Mechanisms and Structure 7.sup.thed., J. Wiley & Sons (New York, NY 2013); Singleton, Dictionary of DNA and Genome Technology 3.sup.rd ed., Wiley-Blackwell (Nov. 28, 2012); and Green and Sambrook, Molecular Cloning: A Laboratory Manual 4th ed., Cold Spring Harbor Laboratory Press (Cold Spring Harbor, NY 2012), provide one skilled in the art with a general guide to many of the terms used in the present application. For references on the preparation and structure of antibodies and fusion polypeptides, see, e.g., Greenfield, Antibodies A Laboratory Manual 2.sup.nd ed., Cold Spring Harbor Press (Cold Spring Harbor NY, 2013); Khler and Milstein, Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion, Eur. J. Immunol. 1976 July, 6(7):511-9; Queen and Selick, Humanized immunoglobulins, U.S. Pat. No. 5,585,089 (1996 December); and Riechmann et al., Reshaping human antibodies for therapy, Nature 1988 Mar. 24, 332(6162):323-7. See also, Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991), Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)), Huston et al., Proc. Natl. Acad. Sci. U.S.A., 85, 5879-5883 (1988), Bird et al., Science 242, 423-426 (1988), Brinkman et al. mAbs Vol 9, No. 2, 182-212 (2017), Chothia & Lesk, J. Mol. Biol, 196:901-917 (1987), Chothia et al., Nature 342:877-883 (1989)), Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448; Poljak (1994) Structure 2: 1121-1123); Kontermann and Dubel eds., Antibody Engineering, Springer-Verlag, N.Y. (2001), p. 790 (ISBN 3-540-41354-5, Zapata et al. (1995) Protein Eng. 8(10): 1057-1062; Morrison, et al., Proc. Natl. Acad. Sci. USA, 81:6851 (1984), U.S. Pat. Nos. 4,816,567, 5,693,780, which are incorporated herein by reference in their entireties.
[0252] One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. Indeed, the present invention is in no way limited to the methods and materials described. For purposes of the present invention, the following terms are defined below.
[0253] As used herein, the term extracellular vesicle and vesicle are used interchangeably and refer to a particle, wherein the particle comprises a phospholipid bilayer that encloses an internal space and an exterior surface and may or may not be derived from a cell. The size of extracellular vesicles can range between 20 nm to 3 m in diameter but may be smaller than 20 nm or larger than 3 m. Examples of extracellular vesicles include, but is not limited to, exosomes (for example small exosomes and large exosomes), ectosomes, macrovesicles, microparticles, apoptotic bodies, vesicular organelles, oncosomes (for examples large oncosomes), exospheres, exomeres, cell derived nanovesicles (CDN) (e.g., by genesis via grating or shearing cells), liposomes or the like known by one of ordinary skill in the art. Extracellular vesicles may originate naturally via known or unknown biosynthetic pathways. Extracellular vesicles may be promoted to originate by using mechanical methods such as cell grating or cell shearing wherein a cell is grated or sheared causing portions or parts of the cell membrane to from vesicles. For example, CDNs may be formed by using mechanical methods such as cell grating or cell shearing wherein a cell is grated or sheared causing portions or parts of the cell membrane to from vesicles. Additional non-limiting examples of mechanical methods that can be used to form cell derived nanovesicles are further described in detail, e.g., Goh, W. J., Zou, S., Ong, W. Y. et al. Bioinspired Cell-Derived Nanovesicles versus Exosomes as Drug Delivery Systems: a Cost-Effective Alternative. Sci Rep 7, 14322 (2017). https://doi.org/10.1038/s41598-017-14725-x, the contents of which are incorporated herein by reference in their entireties.
[0254] Extracellular vesicles comprise cargo, wherein the term cargo refers to peptides, proteins, nucleic acids, lipids, metabolites, carbohydrates, biomolecules, small molecules, large molecules, vesicles, organelles, or fragments thereof. In some embodiments, cargo may refer to existing drugs or therapeutics known in the art. Extracellular vesicle cargo may be located within the internal space of the extracellular vesicle. Extracellular vesicle cargo may be membrane bound and span one or both layers of the extracellular vesicle phospholipid bilayer (for example a transmembrane protein). Extracellular vesicle cargo may be in contact with the external or internal surface of the extracellular vesicle, for example through a covalent bond or a non-covalent bond. The phospholipid bilayer of the extracellular vesicle may comprise one or more transmembrane proteins, wherein a portion of the one or more transmembrane membrane proteins is located within the internal space of the extracellular vesicle. The phospholipid bilayer of the extracellular vesicle may comprise one or more transmembrane proteins, wherein the one or more transmembrane membrane proteins comprises a domain on the exterior of the extracellular vesicle. The phospholipid bilayer of the extracellular vesicle may comprise one or more transmembrane proteins, wherein the one or more transmembrane membrane proteins comprises a domain on the interior of the extracellular vesicle. Cargo may refer to a protein on the luminal side (e.g., in the internal space) of the extracellular vesicle wherein said protein encodes a vesicle targeting domain that may be in contact with the interior phospholipid layer of the extracellular vesicle. Cargo may refer to a protein on the luminal side (e.g., in the internal space) of the extracellular vesicle wherein said protein encodes a vesicle targeting domain that may be in contact with the interior phospholipid layer of the extracellular vesicle and wherein said protein may be presented into the internal space of the extracellular vesicle.
[0255] As used herein, the terms sticky binder and vesicle targeting domain and anchor protein are used interchangeably and refer to a protein that is covalently or non-covalently attached to at least one lipid wherein the one or more lipid is embedded within a membrane (e.g., a cell membrane), and the lipid serves to anchor the protein to the membrane. The terms sticky binder and vesicle targeting domain and anchor protein can also mean a protein sequence that encodes for one or more transmembrane domains wherein the one or more transmembrane domains spans at least partly through a phospholipid bilayer, for example the phospholipid bilayer of an extracellular vesicle. The transmembrane domain can be of a Type I or Type II membrane protein. Transmembrane domains can be structurally identified using methods known to those of skill in the art, such as sequence analysis programs that identify hydrophobic and hydrophilic domains (for example TMHMM Server, v. 2.0DTU, Erik L. L. Sonnhammer, Gunnar von Heijne, and Anders Krogh: A hidden Markov model for predicting transmembrane helices in protein sequences. In Proc. of Sixth Int. Conf. on Intelligent Systems for Molecular Biology, p 175-182 Ed J. Glasgow, T. Littlejohn, F. Major, R. Lathrop, D. Sankoff, and C. Sensen Menlo Park, CA: AAAI Press, 1998, which is incorporated herein by reference in its entirety.)
[0256] A vesicle targeting domain may include, but is not limited to, one or more prenylation site, fatty acylation site, and/or glycosylphosphatidylinositol (GPI) linked protein. One preferred embodiment of a vesicle targeting domain is the GPI sequence from CD55. Another preferred embodiment of a vesicle targeting domain is the GPI sequence from CD59. Another embodiment of a vesicle targeting domain is the C1C2 domain from MFGE8. Other embodiments of sequences for vesicle targeting domains include transmembrane regions of CD9 (for example transmembrane 2 or 3 of CD9, CD9tm2 or CD9tm3, respectively), K-Ras (for example K-Ras4A and K-Ras4B), transmembrane domain from A Disintegrin and Metalloproteinase Domain-containing protein 10 (ADAM10, also known as CDw156 or CD156c) or other ADAM proteins. Vesicle targeting domains may include one or more sequences from 4F2 (for example 4F2 encoded by the solute carrier family 3 member 2 (SLC3A2) gene which makes up the heavy subunit of CD98). Vesicle targeting domains can include a sequence for one or more myristoylation sites. For example, the protein sequence for a myristoylation site from myristoylated alanine-rich C-kinase substrate (MARCKS) protein. Vesicle targeting domains can include a sequence for one or more palmitoylation sites. For example, the myristoylation sequence from the MARCKS protein may be modified to encode for a palmitoylation site. All variants, isoforms, or fragments or the like known by one of ordinary skill in the art are encompassed by the present invention.
[0257] Vesicle targeting domains may include transmembrane sequences from Homo sapiens transferrin receptor 2 (TFR2), transcript variant 1 (transferrin receptor protein 2 isoform 1) or versions therefore. In a preferred embodiment, the vesicle targeting domain may be a transmembrane domain from CD298.
[0258] As used herein, the terms proteins and peptides and polypeptides are used interchangeably herein to designate a series of amino acid residues connected to the other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues. Although protein is often used in reference to relatively large polypeptides, and peptide is often used in reference to small polypeptides, usage of these terms in the art overlaps and varies. The term peptide as used herein refers to peptides, polypeptides, proteins and fragments of proteins, unless otherwise noted. The terms protein and peptide are used interchangeably herein when referring to a gene product and fragments thereof. Thus, exemplary peptides or proteins include gene products, naturally occurring proteins, homologs, orthologs, paralogs, fragments and other equivalents, variants, fragments, and analogs of the foregoing.
[0259] As used herein, the term linker refers to a synthetic protein sequence of amino acids that is used to connect two polypeptide domains via peptide bonds.
[0260] As used herein, the term fusion protein refers to a single chimeric protein comprising a protein of interest (e.g., checkpoint protein) joined to an exogenous protein or protein fragment (e.g., an anchor protein), wherein the components of the fusion protein are linked to each other by peptide-bonds, either directly or through a peptide linker. The anchor protein of the fusion protein may enhance incorporation of the fusion protein onto and/or into the membrane of a vesicle, for example the internal and/or external leaflet of the phospholipid bilayer of an exosome membrane. The fusion protein may have at least a part of an amino acid sequence of an immune checkpoint protein or proteins involved in immune synapses. The fusion protein may have at least a part of an amino acid sequence of A2AR, VTCN1, Galectin 9, FGL-1, PECAM-1, TSG-6, STAB-1, NRP1, NRP2, SEMA3A, SEMA3F, RGMB, TIM-3, TIGIT, HLA class I, HLA class II, VISTA, HMGB1, phosphatidylserine, T-cell receptor (TCR), SHP-1, SHP-2, FBXO38, SH2D1A, B7RP1, IDO, NOX2, TNFRSF18, B7-H4, B7-H5, SISP1, B7-H6, B7-H7, APLNR, IFN , PD-1, WNT5A, IL-6, IL-10, NKG2 family of C-type lectin receptors, ligands of NKG2 family, killer cell immunoglobulin-like receptors, CD2, CD4, CD8, CD27, CD27 ligand (CD70), CD28, CD28H, CD39, CD40, CD44, CD47, CD63, CD66a, CD80, B7-2, CD86, CD73, CD94, CD96, CD101, CD112, CD112R, CD122, CD134, CD137 (4-1BB), CD137 ligand (4-1BBL), CD152, CD154, CD155, CD158, CD158a, CD158g, CD158h, KIR2DL1, KIR2DS1, KIRDS3, KIR2DS5, CD160, CD172a, CD200, CD200R, CD223, CD226, CD252, CD270, CD272, CD273, CD274, CD275, CD276, CD278, CD279 (PD-1), CD279 ligand (PD-L1/PDL-2), CD328, CD329, and/or CD337. The fusion protein may have a polypeptide linker sequence (e.g., an Fc domain and/or a GSSG linker), followed by an amino acid sequence coding for an anchor protein sequence (e.g., a prenylation site, fatty acylation site, or a GPI sequence) or any isoform, fragment, variation thereof, or a ligand to the aforementioned proteins thereof, or the like known by one of ordinary skill in the art. All variants are encompassed by the present invention.
[0261] As used herein, the term immune synapse and cell synapse are used interchangeably and refer to cell-to-cell interaction wherein said interaction results in activation, suppression, and/or adhesion of either one or more cells. Immune synapse or cell synapse are mediated by proteins that may be cytoplasmic, membrane bound, membrane associated, and/or secreted. Immune or cell synapses may be mediated by one or more immune checkpoint proteins which herein refers to any protein that is involved in maintaining immune homeostasis or plays a role in regulating immune activation or suppression. Immune checkpoint proteins may be cytoplasmic, membrane bound, membrane associated, and/or secreted.
[0262] As used herein, the term fragment or active fragment refers to a portion of a nucleic acid or polypeptide provided herein that retains the ability to be expressed by the engineered EVs provided herein. In some embodiments, the active fragment retains the ability to activate a target polypeptide, thereby increasing the activity of said target polypeptide (e.g., suppressing an immune response).
[0263] As used herein, the terms specifically bind and/or specifically recognize or substantially binds refers to the affinity of a binding molecule for a target molecule compared to the binding molecule's affinity for non-target molecules. A binding molecule (e.g., a POI domain) that specifically binds a target molecule (e.g., a target polypeptide provided herein) does not substantially recognize or bind non-target molecules. e.g., an antibody specifically binds and/or specifically recognize another molecule, meaning that this interaction is dependent on the presence of the binding specificity of the molecule structure, e.g., an antigenic epitope. As used herein, non-specific binding and background binding refers to the interaction that does not depend on the presence of specific structure (e.g., a specific antigenic epitopes). Methods of measuring binding of a polypeptide to a target are known in the art (e.g., differential scanning calorimetry, isothermal titration calorimetry, spectroscopy, crystallography, surface plasmon resonance, co-immunoprecipitation, pulldown assays, crosslinking, yeast two-hybrid system, tandem affinity purification-mass spectroscopy, protein microarrays, bio-layer interferometry, far-Western blots, computational prediction, analytical ultracentrifugation, light scattering, fluorescence spectroscopy, resonance energy transfer, ELISA or ELISPOT assays, or the like known by one of ordinary skill in the art).
[0264] As used herein, the terms treat, treatment, treating, or amelioration refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with, a disease or disorder. The term treating includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder associated with an infection or a cancer. Treatment is generally effective if one or more symptoms or clinical markers are reduced. Alternatively, treatment is effective if the progression of a disease is reduced or halted. That is, treatment includes not just the improvement of symptoms or markers, but also a cessation or at least slowing of progress or worsening of symptoms that would be expected in absence of treatment. Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. The term treatment of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).
[0265] As used herein preventing or prevention refers to any methodology where the disease state does not occur due to the actions of the methodology (such as, for example, administration of a composition or construct as described herein). In one aspect, it is understood that prevention can also mean that the disease is not established to the extent that occurs in untreated controls. Accordingly, prevention of a disease encompasses a reduction in the likelihood that a subject can develop the disease, relative to an untreated subject (e.g., a subject who is not treated with the methods or compositions described herein).
[0266] As used herein, the terms autoimmune condition and autoimmune disease are used interchangeably and refer to any disease characterized by abnormal functioning of the immune system and may include, but is not limited to, achalasia, Addison's disease, adult Still's disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM/Anti-TBM nephritis, antiphospholipid syndrome, autoimmune angioedema, autoimmune dysautonomia, autoimmune encephalomyelitis, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune urticaria, axonal & neuronal neuropathy (AMAN), Bal disease, Behcet's disease, benign mucosal pemphigoid, bullous pemphigoid, Castleman disease, celiac disease, Chagas disease, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic recurrent multifocal osteomyelitis (CRMO), Churg-Strauss syndrome (CSS), eosinophilic granulomatosis (EGPA), cicatricial pemphigoid, Cogan's syndrome, cold agglutinin disease, congenital heart block, coxsackie myocarditis, CREST syndrome, Crohn's disease, dermatitis herpetiformis, dermatomyositis, Devic's disease (neuromyelitis optica), discoid lupus, Dressler's syndrome, endometriosis, eosinophilic esophagitis (EoE), eosinophilic fasciitis, erythema nodosum, essential mixed cryoglobulinemia, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture's syndrome, granulomatosis with polyangiitis, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, hemolytic anemia, Henoch-Schonlein purpura (HSP), Herpes gestationis or pemphigoid gestationis (PG), hidradenitis suppurativa (HS) (acne inversa), hypogammalglobulinemia, IgA nephropathy, IgG4-related sclerosing disease, immune thrombocytopenic purpura (ITP), inclusion body myositis (IBM), interstitial cystitis (IC), juvenile arthritis, type 1 diabetes, juvenile myositis (JM), Kawasaki disease, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease (LAD), lupus, lyme disease chronic, Meniere's disease, microscopic polyangiitis (MPA), mixed connective tissue disease (MCTD), Mooren's ulcer, Mucha-Habermann disease, multifocal motor neuropathy (MMN) or MMNCB, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neonatal Lupus, neuromyelitis optica, neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism (PR), PANDA, paraneoplastic cerebellar degeneration (PCD), paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, pars planitis (peripheral uveitis), Parsonage-Turner syndrome, pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia (PA), POEMS syndrome, polyarteritis nodosa, polyglandular syndromes type I, II, III, polymyalgia rheumatica, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, primary biliary cirrhosis, primary sclerosing cholangitis, progesterone dermatitis, psoriasis, psoriatic arthritis, pure red cell aplasia (PRCA), pyoderma gangrenosum, Raynaud's phenomenon, reactive arthritis, reflex sympathetic dystrophy, relapsing polychondritis, restless legs syndrome (RLS), retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjgren's syndrome, sperm & testicular autoimmunity, stiff person syndrome (SPS), subacute bacterial endocarditis (SBE), Susac's syndrome, sympathetic ophthalmia (SO), takayasu's arteritis, temporal arteritis/Giant cell arteritis, thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome (THS), transverse myelitis, type 1 diabetes, ulcerative colitis (UC), undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vitiligo, Vogt-Koyanagi-Harada disease. An autoimmune condition or autoimmune diseases may be caused by, but not limited to, a natural predisposition, a infection (e.g., bacteria or virus), drugs, vaccination, environmental triggers (e.g., toxins or chemicals such as dust, silica, oil, benzene, tri- or per-chloroethylene etc.), stress, cancer, blood or tissue or organ transplantation, or unknown etiology. Autoimmune disorders may result in but not limited to the destruction of body tissue, abnormal growth of an organ or tissue, changes in organ or tissue function (e.g., changes in blood vessels, connective tissue, function of endocrine glands, joints, muscles, blood cells, skin, etc.).
[0267] As used herein, the term cancer refers to a hyperproliferation of cells that exhibit a loss of normal cellular control that results in unregulated growth, lack of differentiation, local tissue invasion, and metastasis. The methods and compositions described herein can be used for the treatment of solid tumors (e.g., cancer) or non-solid tumors, such as leukemia, blood cell cancers, and the like. Solid tumors can be found in bones, muscles, the brain, or organs, and can be sarcomas or carcinomas. Where the methods and compositions described herein can overcome barriers of tumor treatment, including, but not limited to barriers to treatment or inhibition of metastases, it is contemplated that aspects of the technology described herein can be used to treat all types of solid and non-solid tumor cancers, including cancers not listed in the instant specification. The compositions and methods described herein, without limitation, include methods of treating cancer, methods of inhibiting metastases, and methods of inducing an anti-tumor immune response.
[0268] As used herein, the terms subject, individual, host, and patient are used interchangeably and may refer to any animal, mammal, bird, fish, reptile, and amphibian, for example, human, monkey, dog, cat, horse, pig, cattle, ox, donkey, rabbit, sheep, goat, mouse, rat, guinea pig, llama, chicken, goose, duck, turkey, or the like receiving or registered to receive a therapeutic amount of a composition of the present invention for medical care or treatment.
[0269] As used herein, the term injection refers to any process or method which allows the person skilled in the art to administer any therapeutic to a target site by penetration. Examples of injection are, but not limited to, subcutaneous, subcuticular, subcapsular, subarachnoid, intradermal, intramuscular, intravenous, intra-arterial, intraventricular, intracapsular, intraorbital, intraocular, intrathoracic, intraperitoneal, intravitreal, retro-orbital, intranasal, intracerebral, intrathymic, intraspinal, intrasternal, intra-articular, intracavernous, intracardiac, intraosseous, intrathecal, transtracheal, epidural, or the like as known in the art. A therapeutic does of the present invention may be delivered to a patient by means of controlled release, for example but not limited to, implantable pump and implantable cannulas to provide continuous access to the venous or arterial system.
[0270] As used herein, the term topical application refers to applying or spreading a composition of the present invention onto surfaces on or in the body, both internally and/or externally, in a therapeutically effective amount for local and/or systemic treatment. Topical application may be epicutaneous wherein a composition of the present invention may be directly applied onto a localized surface of the skin or mucous membranes. Topical application may include transdermal application wherein a composition of the present invention may be absorbed into the body to obtain systemic delivery and systemic distribution. For example, a transdermal patch may be applied onto the body to deliver a therapeutic dose of a composition of the invention presented herein. Topical application formulations may include, but are not limited to, creams, foams, gels, lotions, solutions, ointments, dermal patch, transdermal patches, powder, solid, sponge, tape, vapor, paste, film, liposomes, balm, shampoo, spray, or tincture. A therapeutic dose of a composition of the present invention may be delivered vaginally (for example a vaginal suppository, vaginal ring, douche, intrauterine device, intravesical infusion, and the like) or urethra.
[0271] As used herein, the term enteral administration refers to a composition of the present invention administered via the gastrointestinal tract in a therapeutically effective amount for local or systemic treatment. Enteral administration may include, but is not limited to, delivery of a composition of the present invention via the mouth, sublingual, esophagus, gastric (for example the stomach), small intestines, large intestines or rectum. Oral delivery of the present invention may include, but is not limited to, the use of a capsule, pastille, pill, tablet, solution, gel, suspension, emulsion, syrup, elixir, tincture, mouthwash, lozenges, chewing gum, lollipop, osmotic-controlled release oral delivery system, or the like. Gastric delivery may involve the use of a tube or nasal passage that leads directly to the stomach, for example, a percutaneous endoscopic gastrostomy tube. Gastric delivery may involve direct injection made through the abdominal wall. Rectal delivery may involve, but is not limited to, the use of a suppository, ointment, enema, murphy drip, or the like. A therapeutic does of the present invention may be delivered to a patient by means of controlled release, for example but not limited to, controlled release drug delivery pellet or pill.
[0272] As used herein, the terms pulmonary system or respiratory system are used interchangeably and refer, but are not limited, to the respiratory region, conducting airways, nasal cavity, sinuses, nasopharynx, oropharynx, larynx, trachea, bronchi, bronchioles, respiratory bronchioles, alveolar ducts, alveolar sacs, respiratory epithelium (e.g., alveolar epithelial cells), endothelial cells, or the like.
[0273] As used herein, the terms pulmonary delivery and pulmonary administration are used interchangeably and refer to delivering a composition of the present invention to the respiratory system through the respiratory route, including but not limited to, intranasal administration, oral administration, and oral inhalative administration (e.g., intratracheal instillation and intratracheal inhalation) of a therapeutically effective amount for local or systemic treatment. Pulmonary delivery of a therapeutically effective amount of a composition of the present invention may be achieved by dispersion, for example by using a syringe. Pulmonary delivery of a composition of the present invention may be achieved by aerosol administration, wherein aerosol administration may deposit a therapeutically effective amount of the present invention by gravitational sedimentation, inertial impaction, or diffusion.
[0274] Pulmonary delivery of a therapeutically effective amount of a composition of the present invention may be deposited on any mucus layer of the respiratory system, for example, but not limited to, the mucus layer which coats the walls of conducting airways, the smaller airway, and/or alveolar space.
[0275] As used herein, an appropriate control refers to an untreated, otherwise identical cell or population (e.g., a subject who was not administered the composition described herein, or was administered by only a subset of agents provided herein, as compared to a non-control cell).
[0276] As used herein, a reference level can refer to one or more parameters or markers as measured for a normal, otherwise unaffected cell population or tissue (e.g., a biological sample obtained from a healthy subject, or a biological sample obtained from the subject at a prior time point, or a biological sample that has not yet been contacted with a pathogen as described herein). For measuring or monitoring therapeutic efficacy, a level determined prior to treatment or earlier in treatment can also provide a reference level for a given parameter or value.
[0277] As used herein, the term modulates refers to an effect including increasing or decreasing a given parameter as those terms are defined herein.
[0278] The terms increased, increase, increases, or enhance or activate are all used herein to generally mean an increase of a property, level, or other parameter by a statistically significant amount; for the avoidance of any doubt, the terms increased, increase or enhance or activate means an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, at least about a 20-fold increase, at least about a 50-fold increase, at least about a 100-fold increase, at least about a 1000-fold increase or more as compared to a reference level. For example, increasing activity can refer to activating a receptor or a signaling pathway (e.g., antibody production or inflammation).
[0279] The terms decrease, reduced, reduction, or inhibit are all used herein to mean a decrease or lessening of a property, level, or other parameter by a statistically significant amount. In some embodiments of any of the aspects, reduce, reduction or decrease or inhibit typically means a decrease by at least 10% as compared to a reference level (e.g., the absence of a given treatment) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more.
[0280] As used herein, reduction or inhibition does not encompass a complete inhibition or reduction as compared to a reference level. Complete inhibition is a 100% inhibition as compared to a reference level. A decrease can be preferably down to a level accepted as within the range of normal for an individual without a given disorder.
[0281] As used herein the term comprising or comprises is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the method or composition, yet open to the inclusion of unspecified elements, whether essential or not.
[0282] As used herein the term consisting essentially of refers to those elements required for a given embodiment. The term permits the presence of elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment.
[0283] The term consisting of refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.
[0284] As used in this specification and the appended claims, the singular forms a, an, and the include plural references unless the context clearly dictates otherwise. Thus for example, references to the method includes one or more methods, and/or steps of the type described herein and/or which will become apparent to those persons skilled in the art upon reading this disclosure and so forth. Similarly, the word or is intended to include and unless the context clearly indicates otherwise. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below. The abbreviation, e.g. is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example. Thus, the abbreviation e.g. is synonymous with the term for example.
[0285] The abbreviation, etc. is derived from the Latin et cetera, and is used herein to indicate a non-limiting list. Thus, the abbreviation etc. is synonymous with the term and other similar things, or and so forth.
[0286] Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term about. The term about when used in connection with percentages can mean 10%.
[0287] The term statistically significant or significantly refers to statistical significance and generally means a two-standard deviation (2SD) difference, above or below a reference value. Additional definitions are provided in the text of individual sections below.
[0288] It should be understood that this invention is not limited to the particular methodology, protocols, and reagents, etc., described herein and as such may vary. The terminology used herein is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention, which is defined solely by the claims.
[0289] As used herein and in the claims, the singular forms include the plural reference and vice versa unless the context clearly indicates otherwise. The term or is inclusive unless modified, for example, by either. Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term about.
[0290] Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
[0291] It is to be understood that the foregoing description and the following examples are illustrative only and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments, which will be apparent to those of skill in the art, may be made without departing from the spirit and scope of the present invention. Further, all patents, patent applications, and publications identified are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the present invention. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents are based on the information available to the applicants and do not constitute any admission as to the correctness of the dates or contents of these documents.
[0292] All patents and other publications identified are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that could be used in connection with the present invention. These publications are provided solely for their disclosure prior to the filing date of the present application. Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason. All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents.
[0293] Some embodiments of the technology described herein can be defined according to any of the following numbered paragraphs:
[0294] 1. An engineered extracellular vesicle comprising: [0295] at least one fusion polypeptide comprising: [0296] (i) at least one protein of interest (POI) domain or a fragment thereof, and [0297] (ii) at least one vesicle targeting domain, [0298] wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle.
[0299] 2. The engineered extracellular vesicle of paragraph 1, wherein the extracellular vesicle is an exosome.
[0300] 3. The engineered extracellular vesicle of paragraph 1 or paragraph 2, wherein the protein of interest (POI) domain or a fragment thereof is a N-terminal domain of the fusion polypeptide.
[0301] 4. The engineered extracellular vesicle of any one of paragraphs 1-3, wherein the vesicle targeting domain is a C-terminal domain of the fusion polypeptide.
[0302] 5. The engineered extracellular vesicle of any one of paragraphs 1-4, wherein the fusion polypeptide comprises at least two POI domains and/or at least two exosome targeting domains.
[0303] 6. The engineered extracellular vesicle of any one of paragraphs 1-5, wherein the fusion polypeptide further comprises a peptide linker.
[0304] 7. The engineered extracellular vesicle of any one of paragraphs 1-6, wherein the fusion polypeptide further comprises a fragment crystallizable region (Fc) domain.
[0305] 8. The engineered extracellular vesicle of any one of paragraphs 1-7, wherein the vesicle targeting domain is in a luminal position relative to the lipid membrane of the extracellular vesicle.
[0306] 9. The engineered extracellular vesicle of any one of paragraphs 1-7, wherein the vesicle targeting domain in an exterior position relative to the lipid membrane of the extracellular vesicle.
[0307] 10. The engineered extracellular vesicle of any one of paragraphs 1-9, wherein the POI domain is selected from the group consisting of: Table 1.
[0308] 11. The engineered extracellular vesicle of any one of paragraphs 1-10, wherein the POI domain is PD-L1 or a fragment thereof.
[0309] 12. The engineered extracellular vesicle of any one of paragraphs 1-11, wherein the POI domain is PD-L2 or a fragment thereof.
[0310] 13. The engineered extracellular vesicle of any one of paragraphs 1-12, wherein the POI domain is FGL1 or a fragment thereof.
[0311] 14. The engineered extracellular vesicle of any one of paragraphs 1-13, wherein the POI domain is 4-1BBL or a fragment thereof.
[0312] 15. The engineered extracellular vesicle of any one of paragraphs 1-14, wherein the POI domain is CTLA-4 or a fragment thereof.
[0313] 16. The engineered extracellular vesicle of any one of paragraphs 1-15, wherein the POI domain substantially binds to one or more of a target polypeptide.
[0314] 17. The engineered extracellular vesicle of paragraph 16, wherein the target polypeptide is selected from the group consisting of: Table 2.
[0315] 18. The engineered extracellular vesicle of any one of paragraphs 1-17, wherein the vesicle targeting domain is selected from the group consisting of; Table 3.
[0316] 19. The engineered extracellular vesicle of any one of paragraphs 1-18, wherein the linker is in an exterior position relative to the lipid membrane of the extracellular vesicle.
[0317] 20. The engineered extracellular vesicle of any one of paragraphs 1-18, wherein the linker is a transmembrane linker.
[0318] 21. The engineered extracellular vesicle of any one of paragraphs 1-18, wherein the linker is in a luminal position relative to the lipid membrane of the extracellular vesicle.
[0319] 22. The engineered extracellular vesicle of any one of paragraphs 1-21, wherein the extracellular vesicle does not comprise an endogenous POI polypeptide.
[0320] 23. A composition comprising a plurality of the engineered extracellular vesicles of any one of paragraphs 1-22.
[0321] 24. The composition of paragraph 23, further comprising a pharmaceutically acceptable carrier.
[0322] 25. An engineered extracellular vesicle comprising: [0323] (a) a first fusion polypeptide comprising: [0324] (i) at least one protein of interest (POI) domain or a fragment thereof, and [0325] (ii) at least one vesicle targeting domain, [0326] wherein the at least one POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle, [0327] (b) a second fusion polypeptide comprising: [0328] (i) at least one protein of interest (POI) domain or a fragment thereof; and [0329] (ii) at least one vesicle targeting domain, [0330] wherein the POI domain is in an extracellular position relative to a lipid membrane of the extracellular vesicle, [0331] and wherein the at least one vesicle targeting domain is within a lipid membrane of the extracellular vesicle.
[0332] 26. A composition comprising two or more of the engineered extracellular vesicles selected from any one of paragraphs 1-25.
[0333] 27. An extracellular vesicle composition comprising: [0334] a plurality of artificial synapses, [0335] wherein each artificial synapse comprises (i) an extracellular vesicle; (ii) one or more sticky binders; and (iii) one or more signaling domains.
The composition of paragraph 27, wherein the extracellular vesicle comprises an exosome.
[0336] 28. The composition of paragraph 27, wherein the one or more sticky binders is selected from the group consisting of: a GPI anchor, a fatty acetylation site, and a prenylation site.
[0337] 30. The composition of paragraph 27, wherein the signaling domain comprises one or more of: PD-L1, PD-L2, CTLA-4 (CD152), 4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9, PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoform beta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4, TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1, BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L (CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150), CD40, CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL, TIM-1 (CD365), PD-1, or active fragment thereof.
[0338] 29. A method of producing the engineered extracellular vesicle or the composition of any one of paragraphs 1-30, comprising: [0339] (a) providing a population of cells expressing a vector construct encoding one or more sticky binder and one or more signaling domains; and [0340] (b) isolating a plurality of artificial synapses from the population of cells.
[0341] 30. A method of producing the engineered extracellular vesicle or the composition of any one of paragraphs 1-30, comprising: [0342] (a) providing a population of cells expressing a vector construct encoding one or more sticky binder and one or more signaling domains; and [0343] (b) isolating a plurality of artificial synapses from the population of cells; and [0344] (c) purifying the plurality of artificial synapses from the population of cells.
[0345] 33. The method of paragraph 31 or paragraph 32, the isolating is via size exclusion chromatography.
[0346] 34. The method of paragraph 32, wherein the purifying is via multimodal chromatography.
[0347] 35. The method of any of paragraphs 31-34, further comprising performing an assay for POI binding to a target polypeptide.
[0348] 36. The method of paragraph 35, wherein the vector construct further encodes a promoter.
[0349] 37. The method of paragraph 36, wherein the promoter is a tissue-specific promoter or an inducible promotor.
[0350] 38. A method of modulating inflammation in a subject, the method comprising: administering a composition comprising a plurality of engineered extracellular vesicles to a subject in need thereof,
wherein the engineered extracellular vesicles comprise at least one fusion polypeptide comprising: [0351] (i) at least one protein of interest (POI) domain or a fragment thereof; and [0352] (ii) at least one vesicle targeting domain.
[0353] 39. The method of paragraph 38, wherein the extracellular vesicle comprises an exosome.
[0354] 40. The method of any one of paragraphs 38-39, further comprising selecting a subject that has or is suspected of having an autoimmune disease or an inflammatory disease or condition.
[0355] 41. The method of any one of paragraphs 38-40, wherein the vesicle targeting domain is selected from the group consisting of: a Glycosylphosphatidylinositol (GPI) anchor, a fatty acetylation site, and a prenylation site.
[0356] 42. The method of any one of paragraphs 38-41, wherein the vesicle targeting domain is a GPI anchor.
[0357] 43. The method of any one of paragraphs 38-41, wherein the vesicle targeting domain is C1C2.
[0358] 44. The method of any one of paragraphs 38-43, wherein the protein of interest (POI) domain comprises one or more of: PD-L1, PD-L2, CTLA-4 (CD152), 4-1BBL (CD137L), HVEM (CD270), FGL1, OX-2 (CD200), Galectin-9, PVR (CD155), Nectin-2 (CD112) isoform alpha, Nectin-2 (CD112) isoform beta, Nectin-2 (CD112) isoform delta, IL-10, TSG-6, B7-H3 (CD276), B7-H4 (VTCN1), B7-H5 (VISTA), B7-H7 (HHLA2), BTNL1, VSIG8, VSIG3 (IGSF11), VSIG4, TIM-3 (HAVCR2), TIM-4 (TIMD4), CEACAM1, BTN3A1, BTN3A2, BTN2A1, BTNL8, BTN2A2, BTN1A1, TIGIT, CD27L (CD70), CD30L (CD153), GITRL, CD40L (CD154), LIGHT (CD258), TL1, CD80, CD86, LFA-3 (CD58), SLAM (CD150), CD40, CD28, CD28H, CD2, LFA-3 (CD58), CD48, CD226, DR3, DcR3, FasL, TIM-1 (CD365), PD-1, or active fragment thereof.
[0359] 45. The method of any one of paragraphs 38-44, wherein the protein of interest (POI) domain is PD-L1 or a fragment thereof.
[0360] 46. The method of any one of paragraphs 38-44, wherein the protein of interest (POI) domain is PD-L2 or a fragment thereof.
[0361] 47. The method of any one of paragraphs 38-44, wherein the protein of interest (POI) domain is CTLA-4 or a fragment thereof.
[0362] 48. The method of any one of paragraphs 38-44, wherein the protein of interest (POI) domain is HVEM or a fragment thereof.
[0363] 49. The method of paragraph 40, wherein the inflammatory disease and/or condition is acute.
[0364] 50. The method of paragraph 40, wherein the inflammatory related disease and/or condition is chronic.
[0365] 51. The method of paragraph 38, wherein administering the composition comprises injection, topical administration, or inhalation.
[0366] 52. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising:
at least one fusion polypeptide comprising: [0367] (i) at least one protein of interest (POI) domain or a fragment thereof; and [0368] (ii) at least one vesicle targeting domain for the treatment of an inflammatory disease or condition.
[0369] 53. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising:
at least one fusion polypeptide comprising: [0370] (i) at least one protein of interest (POI) domain or a fragment thereof; and [0371] (ii) at least one vesicle targeting domain for the treatment of an autoimmune disease or condition.
[0372] 54. Use of a composition comprising a plurality of engineered extracellular vesicles, the engineered extracellular vesicles each comprising:
at least one fusion polypeptide comprising: [0373] (i) at least one protein of interest (POI) domain or a fragment thereof; and [0374] (ii) at least one vesicle targeting domain for the treatment of cancer.
EXAMPLES
[0375] The following examples are provided by way of illustration, not limitation.
Example 1
Design of an Artificial Synapse
[0376] As described, artificial synapses are engineered to induce and propagate biological signaling, including for example, antagonist and agonist signaling. Artificial synapses are designed to include hallmark biophysical and biochemical features of extracellular vesicles, further including vesicle targeting domains and signaling domains. Vesicle targeting domains capable of attaching to extracellular vesicles such as exosomes, signaling domains, optionally including a linker (e.g., Fc linker), can be organized in genetic vector constructs. Designs are shown in
[0377] Sticky binders are extracellular vesicle targeting sequences. Preliminary extracellular vesicle targeting sequences of interest are from, but not limited to, 4F2 (CD98), ADAM10, CD298, TFR2, transmembrane domains of CD9, MARCKS, KRAS, etc. or the like as appreciate by one of ordinary skill in the art. The Inventors discovered high efficiency when proteins are engineered with a GPI domain. Optionally, linker regions such as an Fc linker between the vesicle targeting domains and signaling domains can be added.
[0378] A variety of signaling domains are of interest with proof-of-concept examples including PD-L1, PD-L2 and CTLA-4 (CD152). Artificial synapses including these three signaling domains are shown in
[0379] Each of these elements are described in the following non-limiting examples.
Example 2
Genetic Constructs
[0380] Examples of constructs including these variable elements (e.g., sticky binders GPI or C1C2, or signaling domains including PD-L1, PD-L2 and CTLA-4 (CD152) were engineered into vectors shown in
Example 3
Purification of hPD-L1 Tagged Artificial Synapses by a Multimodal Resin Marketed for Exosome Purification
[0381] Upon expression of hPD-L1-Fc-GPI in mammalian cells, artificial synapses were further purified using a size exclusion resin marketed for exosome purification. Large MW artificial synapses elute in the first fraction as shown by the high hPD-L1 concentration and exosome quantity (2.26E9 artificial synapses/ml) in elution 1. Clean in place (CIP) fractions show bound and eliminated proteins from the Inventors' exosome elution. Results are shown in
Example 4
hPDL1-Fc-GPI Exosome PurificationSize Exclusion Chromatography Column
[0382] Artificial synapses engineered from exosomes such as hPDL1-Fc-GPI after elution from size exclusion resin marketed for exosome purification can be further purified via a size exclusion column as shown here. Using a size exclusion chromatography (SEC), artificial synapses elute in fractions 7-9. Total protein (determined by qBit) and hPD-L1 ng/ml (determined by ELISA) of each fraction is shown in the graph. Bars show exosome number per ml (i.e., 1E10 artificial synapses/ml etc.). Fractions 7-9 contain >99% purified artificial synapses. Fractions 7-9 are pooled and may be concentrated using a filtration device, for example a 10K MWCO Amicon Centrifugal Filter. Final purified product is filtered through a low protein binding 0.2 m or 0.45 m filter, for example a PES filter. Results are shown in
Example 5
hPD-L1 Expression on Artificial Synapses
[0383] Exosome quantity and hPD-L1 concentration was determined in SEC fractions 7-9. Knowing the molecular weight of engineered hPD-L1, the Inventors can determine the number of hPD-L1 molecules per exosome to be approximately between 12 to 40 PD-L1/exosome. This value is consistent between different purification runs and constructs. Results are shown in
Example 6
Purification of hPD-L2-Fc-GPI Artificial Synapses Via Multimodal Resin Chromatography Marketed for Exosome Purification
[0384] This graph shows Abs 280 of multimodal resin chromatography fractions and quantity of hPDL2 in indicated fractions. Artificial synapses eluted in Elution 1.
[0385] Clean in place (CIP) fractions show bound and eliminated proteins from the Inventors' exosome elution. Results are shown in
Example 7
PD-L2 Purification Via Size Exclusion Chromatography
[0386] Artificial synapses engineered from artificial synapses such as hPDL2-GPI after elution from size exclusion resin size exclusion resin marketed for exosome purification are further purified via size exclusion chromatography as shown. Results are shown in
Example 8
hCTLA4-Fc-GPI Exosome Purification Via Size Exclusion Chromatography
[0387] Using size exclusion chromatography marketed for exosome purification, artificial synapses elute in fractions 7-9. Total protein (determined by qBit) and hPD-L1 ng/ml (determined by ELISA) of each fraction is shown in the graph. Fractions 7-9 are pooled and contain >99% purified artificial synapses. Pooled artificial synapses engineered from artificial synapses fractions may then be concentrated using a filtration device, for example a 10K MWCO Amicon. Final purified product is filtered through a low protein binding filter, for example a 0.2 m or 0.45 um PES filter. Results are shown in
Example 9
PD-L1 and PD-L2 In Vitro Assay from DiscoverX
[0388] To perform this validation method, the Inventors modified the PathHunter PD-1 Signaling Bioassay from DiscoverX Briefly, the PathHunter PD-1 Signaling Bioassay relies on the well-established PathHunter Enzyme Fragment Complementation (EFC) technology to interrogate receptor activity. EFC consists of a split -galactosidase (-gal) enzyme: the Enzyme Donor (ED) and Enzyme Acceptor (EA) fragments which independently have no -gal activity. However, when forced to complement they form an active -gal enzyme that will hydrolyze substrate to produce a chemiluminescent signal. The PathHunter PD-1 Signaling Bioassay consists of human cells engineered to stably express an ED-tagged PD-1 receptor, while EA is fused to the phosphotyrosine-binding SH2 domain of the intracellular signaling protein, SHP1. Ligand or antibody-induced activation of the receptor results in phosphorylation of the receptor's cytosolic tail. The SH2-domain fused to EA binds the phosphorylated receptor, forcing complementation of ED and EA, resulting in formation of an active -gal enzyme, which hydrolyzes the substrate to produce a chemiluminescent signal. Full-length PD-1 receptor was engineered with a small -gal fragment (ED in red) fused to its C-terminus, and the SH2-domain of SHP1 was engineered with the complementing -gal fragment (EA). These constructs were stably expressed in Jurkat cells (produced by DiscoverX), while PD-L1 and PD-L2 was stably expressed on artificial synapses produced by Diadem Biotherapeutics. Artificial synapses were engineered to have surface expressed human PD-L1 or PD-L2. Briefly, the gene sequence coding for the extracellular domain of human PD-L1 or PD-L2 was linked to the exosome via a glycosylphosphatidylinositol (GPI) linker with an Fc domain between the linker and PD-L1 or PD-L2 (PD-L1-Fc-GPI and PD-L2-Fc-GPI). Additional variations of the Inventors' PD-L1 and PD-L2 artificial synapses include cloning a C1C2 linker (from MFGE8) in place of the GPI linker, and with or without the Fc domain. The Inventors also cloned murine versions of PD-L1 and PD-L2 extracellular domains in place of the human PD-L1 and PD-L2 all variations. Ligand engagement, through addition of ligand-presenting artificial synapses, results in phosphorylation of PD-1, leading to the recruitment of SHP1-EA
[0389] The Inventors obtained approximately 1000higher increase in Relative Light Units (RLU) in Jurkat signaling cells treated with PD-L1 or PD-L2 labeled artificial synapses when compared to soluble PD-L1-Fc or PD-L2-Fc ligand, respectively. Meaning, it took 1000 less ug/ml of PD-L1 or PD-L2 on artificial synapses than solubilized PD-L1-Fc or PD-L2 ligand to achieve the same RLU signaling. Results are shown in
Example 10
PD-L1 In Vivo AssayExperimental Autoimmune Uveoretinitis (EAU) in Lewis Rats Bioassay
[0390] Experimental autoimmune uveoretinitis (EAU) is an organ-specific, T lymphocyte-mediated autoimmune disease, which serves as a model for several human ocular inflammations of an apparently autoimmune nature. There is a statistically significant initial reduction in EAU in mPDL1 artificial synapse treated rats via either the intravitreal and intravenous delivery modes. 2nd intravitreal and 3rd intravenous injections are performed on Day 12. There appears to be a more rapid rate of resolution in the 1 intravitreal and intravenous groups. (C) Simplified view of aforementioned results. (D) Weight of rats was monitored throughout the study. 3rd intravitreal and 4th intravenous injections are performed on Day 16. There does not appear to be any significant change in EAU in any of the test groups. The aforementioned results provide proof of principle of successfully immunizing the rats with human cell derived artificial synapses with mouse PDL1 injected into rats. Results are shown in
Example 11
Engineered Exosome Multivalent Display
[0391] The inventors have developed the following 3 types of protein display on or within exosomes: [0392] Type I membrane proteins wherein the N-Terminus is on the luminal (interior) side of the exosome membrane and the C-Terminus is on the exterior of the exosome. [0393] Type II membrane proteins wherein the N-Terminus is on the exterior while the C-Terminus is on the interior. [0394] Luminal internally loaded proteins which are linked to the exosome by a Myristoylation/Palmitoylation site which attaches proteins to the interior of the exosome membrane.
[0395]
[0396] Additional embodiments or ligands displayed on the exosome surface (Type I and Type II membrane proteins) and internal luminal display can include the following: [0397] Type I: PD-L1, PD-L2, FGL1, OX40L [0398] Type II: 4-1BBL, GITRL, CD27L, CD30L [0399] Luminal: NanoLuc luciferase; Green fluorescent protein (GFP) (e.g., eGFP, etc.); Red fluorescent protein (RFP) (e.g., mScarlet, mCherry, mRuby, tdTomato, etc.); Cyan fluorescent protein (CFP); Yellow fluorescent protein (YFP); A therapeutic protein; and CRISPR/CAS-9
[0400]
Example 12a
Designed and Engineered Human Fusion Polypeptide Constructs
[0401] The inventors have designed, engineered, and purified the following human fusion polypeptide constructs for therapeutic use (
Example 12b
Designed and Engineered Fusion Polypeptide Constructs
[0438] The inventors have designed, engineered, and purified the following mouse fusion polypeptide constructs for therapeutic use (
Example 12c
Designed and Engineered Luminal Loaded Fusion Polypeptide Constructs
[0451] The inventors have designed, engineered, and purified the following fusion polypeptide constructs for internal luminal loading of the fusion polypeptide: [0452] pcDNA5-FRT-Myr-NanoLuc (
Example 13
Purification of Exosomes Labeled with Type I Membrane Fusion Polypeptides
[0454] The inventors have purified engineered EVs, including hPD-L1-GPI; hPDL1-Fc-GPI; hPDL2-Fc-GPI; hCTLA4-Fc-GPI; mPDL1-GPI; and mPD-L1-Fc-GPI. The process for purification and analytical processing of the engineered EVs are shown in the flow chart provided in
[0455] Size exclusion chromatography was performed to purify hPD-L1-GPI (no Fc) exosomes (
[0456] Furthermore, a commercially available multimodal exosome purification resin was also used to purify and isolate PD-L1-GPI exosomes and PD-L1-Fc-GPI exosomes (
[0457] Large MW exosomes elute in the first fraction as shown by the high hPD-L1 concentration and exosome quantity (2.26E9 exosomes/ml) in elution 1. Clean in place (CIP) fractions show bound and eliminated proteins from our exosome elution (
[0458]
Example 14
Comparative Proteomics Analysis of the Engineered EVs
[0459] Fc-GPI enables high density display and has a higher abundance than endogenous PTGFRN or CD81. Therefore, comparison proteomics of transprotein expression and surface labeling on the engineered exosomes, hPD-L1-Fc-GPI; hPD-L2-Fc-GPI; and hCTLA-Fc-GPI, was performed to determine the effects on endogenous protein expression in engineered exosomes. It was confirmed that the fusion polypeptide expression does not affect the relative expression of native and associated exosome proteins (
Example 15
Scale-Up Production and Purification of mPD-L1-Fc-GPI Exosomes Using Microcarriers in a Stirred Tank Single-Use Bioreactor (STR)
[0460] 1E7 HEK 293 cells were utilized for the production of mPDL1-Fc-GPI exosomes. Cells were passaged on SoloHill Microcarriers up to Passage 4, at which point cells were expanded in a 2.5 L Stirred Tank Single-Use Bioreactor. Passage 4 cells were cultured for an additional 5 days and media was harvested on Day 5 and used for exosome purification. The general aim and process is provided below
[0461] AIM: Utilize SoloHill's Xeno-free microcarrier technology to scale up cells for engineering EVs and evaluate Microcarrier-stir tank bioreactor technology for production of therapeutic exosomes in the Xeno-free medium conditions.
Passage 1:
[0462] Thaw vial (1.00E+07) of cells and seed Corning T-150 & CellSTACK2 tissue culture treated flask at 1.00E+04 cells per cm2 seed density. [0463] Perform 100% medium exchange from both flasks on day 3. [0464] Harvest Corning T-150 & CellSTACK2 flasks on day 4 post seeding and seed spinner microcarrier culture.
Passage 2:
[0465] Expand cells in 2200 mL spinner flasks at 10 cm2/mL microcarrier density using SoloHill's Xeno-free prototype microcarrier. [0466] Seed microcarrier cultures at 1.00E+04 cells per cm2 seed density and T-25 as flatware control flask. [0467] Perform 80% batch volume medium exchange from spinners and T-25 flasks on day 3. [0468] Harvest both microcarrier and T-25 flasks on day 4 post seeding and seed spinner microcarrier culture.
Passage 3:
[0469] Expand cells in 3300 mL spinner flasks at 10 cm2/mL microcarrier density using SoloHill's Xeno-free prototype microcarrier. [0470] Seed microcarrier cultures at 1.00E+04 cells per cm2 seed density and T-25 as flatware control flask. [0471] Perform 80% batch volume medium exchange from spinners and T-25 flasks on day 3. [0472] Harvest both microcarrier and T-25 flasks on day 4 post seeding. [0473] Seed microcarrier-stir tank bioreactor for exosome production.
Passage 4:
[0474] Expand cells into a 2.5 L microcarrier-stir tank at 10 cm2/mL surface area to medium ratio. [0475] Seed cultures at 1.00E+04 cells per cm2 seed density and T-25 as flatware control flask. [0476] Perform 80% batch volume medium exchange on day 2. [0477] On day 3 rinse all cultures with 2cell culture volumes of DPBS containing Ca and Mg. [0478] Add exosome production medium (DMEM-1% Glutamax) to all cultures at 10 cm2/mL surface area to medium volume ratio. [0479] On day 5 collect harvest spent medium from all cultures, filter using 0.45 m Nalgene rapid flow system and freeze at 20 C.
Procedures:
[0480] Medium Composition [0481] DMEM 1 (Corning ref #10-013-CV) [0482] 1% Glutamax (Thermo ref #35050061) [0483] 3% Human platelet lysate (Stemulate from Cook Reagentec PG-NH-500)
Cell Harvest Protocol for Planar Culture
[0484] Settle microcarriers and remove maximum volume of spent medium without removing microcarriers. [0485] Wash microcarrier culture with DPBS 2 time at 0.1 mL/cm2 volume to surface area ratio. [0486] Add 37 C. warmed TrypLE 5 enzyme at 0.012 mL/cm2 and incubate flask at room temperature for 15 minutes. [0487] Add complete medium at 0.024 mL/cm2 to quench TrypLE 5 activity. [0488] Perform viable cell count using NC200 cell count instrument.
Nuclei Count Protocol for Microcarrier Culture
[0489] Obtain 4-5 mL of microcarrier culture from bioreactor or spinner flask [0490] Settle microcarriers and remove maximum volume of spent medium without removing microcarriers. [0491] Add 1.5 mL Nucleocounter Reagent A to macrocarrier sample tube and vortex at high speed for a minute. [0492] Add 1.5 mL Nucleocounter Reagent B to macrocarrier sample tube and vortex at high speed for a minute. [0493] Perform nuclei count using NC200 nuclei count instrument.
Medium Collection from STR Bioreactor [0494] Stop all controls and settle microcarriers in the bioreactor vessel. [0495] Pump out medium through screen bag into collection bottle at 200 mL/minute flowrate using peristaltic pump. [0496] Inside BSC pour medium into 0.45 m Nalgene rapid flow filter system and remove free floating cells. [0497] Freeze medium bottles in minus 20 C. freezer.
Medium Collection from Spinner Flasks [0498] Inside BSC pour microcarrier culture into 0.45 m Nalgene rapid flow filter system and remove free floating cells as well as microcarriers. [0499] Freeze medium bottles in minus 20 C. freezer.
TABLE-US-00008 TABLE 6 Cell culture set points Temper- Dissolved ature Agitation Oxygen Incubator % C. rpm (DO) % pH CO.sub.2 setting T - Flask 37 n/a n/a n/a 5 1 CellSTACK 2 37 n/a n/a n/a 5 1 Spinner flask 37 35 n/a n/a 5 1 STR bioreactor 37 35 50 7.35 n/a
[0500]
[0501] mPDL1 was purified using the purification process outlined above (
Example 16
PD-L1-Fc-GPI and PDL2-Fc-GPI Exosomes Increase PD-1 Signaling
[0502] The purified exosomes were tested using the modified DiscoverX Assay in
Example 17
In Vivo AssayTherapeutic Effect of mPD-L1 Exosomes in an Experimental Autoimmune Uveoretinitis (EAU) Model in Lewis Rats
[0503] Lewis rats were challenged with retinal antigen interphotoreceptor retinoid-binding protein (IRBP) peptide. This model can be used to study anterior and posterior chamber dependent EAU. Rats were immunized on Day 1 with EAU presenting typically at Day 6. Clinical scores in the rat were determined. The EAU dosing schedule is shown in
TABLE-US-00009 TABLE 7 EAU dosing test articles Unmodified mPD-L1-Fc-GPI mPD-L1-Fc-GPI mPD-L1 Exosomes Exosomes 1X Exosomes 10X Exosomes (IVT) (IVT) (IVT) (IV) Dose 2 ul 2 ul 2 ul 5 ml/kg Total protein 40 ug/ml 40 ug/ml 400 ug/ml 40 ug/ml concentration Total protein 80 ng/eye 80 ng/eye 800 ng/eye 50 ug/animal administered (~200 ug/kg) Exosome 5.7 10.sup.10/ml 2.34 10.sup.10/ml 2.34 10.sup.11/ml 2.34 10.sup.10/ml concentration Total exosomes 4.7 10.sup.7 4.7 10.sup.7 4.7 10.sup.8 2.93 10.sup.10 administered *IVTintravitreal, IVintravenous
[0504] The study design is outlined below (Table 8):
TABLE-US-00010 TABLE 8 Study design Group Test Article N Route Concentration Dosage Regimen 1 Cyclosporine 8 p.o. 1 mg/mL 10 mg/kg BID from day 0 to Day 20 2 Negative control 8 Intravitreal 1X 2-3 L Day 6, Day 12, (PBS vehicle) both eyes and Day16 3 Unmodified exosomes 8 Intravitreal 1X (~40 ug/ml) 2-3 L Day 6 and (Control exosomes) both eyes Day 12 4 mPD-L1-Fc-GPI 8 Intravitreal 1X (~40 ug/ml) 2-3 L Day 6, Day 12, (40 ug/ml) both eyes and Day16 5 mPD-L1-Fc-GPI 4 Intravenous 1X (~40 ug/ml) 5 mL/kg Day 1, Day 6, (40 ug/ml) Injection Day 12, and Day 16 6 No IRBP peptide 4 Intravitreal 1X (~40 ug/ml) 2-3 L Day 6, Day 12, but treated with both eyes and Day 16 Test Agent B (for tolerability) 7 mPD-L1-Fc-GPI 8 Intravitreal 1X (400 ug/ml) 2-3 L Day 6, Day 12, (400 ug/ml) both eyes and Day 16
[0505] Clinical Scores were determined as follows:
TABLE-US-00011 TABLE 9 EAU Clinical Scores in Rats Score Clinical Criteria 0 No disease; eye is translucent and reflects light(red reflex) 0.5 Dilated blood vessels in the iris (trace) 1 Engorged blood vessels in the iris; abnormal pupil contraction 2 Hazy anterior chamber; decreased red reflex 3 Moderately opaque anterior chamber, but pupil still visible; dull red reflex 4 Opaque anterior chamber and obscured pupil; red reflex absent; proptosis
[0506] Each higher grade includes the criteria of the preceding one.
[0507] It was discovered that there is a statistically significant initial reduction in EAU in mPDL1 exosome treated rats via either the intravitreal and intravenous delivery modes as compared with untreated animals (
Example 18
Purification of Exosomes Labeled with Type II Membrane Proteins
[0508] The inventors designed, engineered, and purified pcDNA5-FRT-4F2-4-1BBL exosomes by the methods provided herein (
Example 19
Purification of Luminal Labeled Exosomes (Internal Loading)
[0509] In addition to Type I and Type II display fusion proteins on the surface of an EV, exosomes can be loaded with fusion proteins that are localized to the lumen of the phopholipid bilayer of the exosome (
[0510] NanoLuc luciferase expressing exosomes were also purified with the Myr/Palm sequence incorporated into the vector encoding the fusion polypeptide. A Qubit fluorometer was used to measure total protein and Promega Nano-Glo substrate and plate luminometer to measure luminescence (