Antigen-specific T cell receptors and T cell epitopes
09586997 ยท 2017-03-07
Assignee
- BioNtech Cell & Gene Therapies GmbH (Mainz, DE)
- Translationale Onkologie an der Universitatsmedizin der Johannes Gutenberg-Universitat Mainz gemeinnutzige GmbH (Mainz, DE)
Inventors
Cpc classification
C07K14/705
CHEMISTRY; METALLURGY
A61P31/00
HUMAN NECESSITIES
A61K40/11
HUMAN NECESSITIES
C12N2710/16134
CHEMISTRY; METALLURGY
A61K40/4202
HUMAN NECESSITIES
A61P43/00
HUMAN NECESSITIES
A61K40/4267
HUMAN NECESSITIES
C07K14/4748
CHEMISTRY; METALLURGY
A61K2039/57
HUMAN NECESSITIES
G01N2333/916
PHYSICS
A61P35/00
HUMAN NECESSITIES
International classification
C07K14/705
CHEMISTRY; METALLURGY
A61K39/00
HUMAN NECESSITIES
Abstract
The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.
Claims
1. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor -chain comprising the T cell receptor -chain sequence of SEQ ID NO: 44 and a nucleic acid encoding a T cell receptor -chain comprising the T cell receptor -chain sequence of SEQ ID NO: 45 or (ii) a nucleic acid encoding a T cell receptor comprising the T cell receptor -chain sequence of SEQ ID NO: 44 and the T cell receptor -chain sequence of SEQ ID NO: 45.
2. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 1.
3. An antigen-specific lymphoid cell produced by transferring into a lymphoid cell (i) a nucleic acid encoding a T cell receptor -chain comprising all three of the CDR sequences of the T cell receptor -chain sequence of SEQ ID NO: 44 and a nucleic acid encoding a T cell receptor -chain comprising all three of the CDR sequences of the T cell receptor -chain sequence of SEQ ID NO: 45 or (ii) a nucleic acid encoding a T cell receptor comprising all three of the CDR sequences of the T cell receptor -chain sequence of SEQ ID NO: 44 and all three of the CDR sequences the T cell receptor -chain sequence of SEQ ID NO: 45.
4. A pharmaceutical composition comprising the antigen-specific lymphoid cell of claim 3.
5. The antigen-specific lymphoid cell of claim 1, wherein the nucleic acid is RNA.
6. The antigen-specific lymphoid cell of claim 5, wherein the RNA is in vitro transcribed RNA (IVT RNA).
7. The antigen-specific lymphoid cell of claim 1, wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
8. The antigen-specific lymphoid cell of claim 1, wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.
9. The antigen-specific lymphoid cell of claim 3, wherein the nucleic acid is RNA.
10. The antigen-specific lymphoid cell of claim 9, wherein the RNA is in vitro transcribed RNA (IVT RNA).
11. The antigen-specific lymphoid cell of claim 3, wherein the lymphoid cell is selected from the group consisting of a lymphocyte, lymphoblast and plasma cell.
12. The antigen-specific lymphoid cell of claim 3, wherein the lymphoid cell is a T cell lacking endogenous expression of a T cell receptor.
Description
FIGURES
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EXAMPLES
(23) The techniques and methods used herein are described herein or carried out in a manner known per se and as described, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual, 2.sup.nd Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. All methods including the use of kits and reagents are carried out according to the manufacturers' information unless specifically indicated.
Example 1
Materials and Methods
(24) Serotyping
(25) An ELISA based on crude lysates of bacteria (CrELISA or Crude Lysate Enzyme-Linked ImmunoSorbent Assay) expressing either full length NY-ESO-1 or the N-terminus of TPTE (amino acids 1-51) was used according to a previously described protocol for determination of IgG autoantibodies (Tureci, O. et al. (2004), J. Immunol. Methods 289, 191-199). CMV-seropositivity was analyzed by a standard ELISA detecting polyclonal CMV-specific IgG responses.
(26) Cell Lines and Reagents
(27) The human lymphoma cell lines SupT1 (ATCC no. CRL-1942) or Jurkat76 (Heemskerk, M. H. et al. (2003), Blood 102, 3530-3540), both lacking surface expression of endogenous TCR, the mouse embryonic fibroblast cell line NIH3T3 (DSMZ no. ACC 59) and the human chronic myeloid leukemia cell line K562 (Lozzio, C. B. & Lozzio, B. B (1975), Blood 45, 321-334) were cultured under standard conditions. K562 cells transiently or stably transfected with HLA allelotypes (Britten, C. M. et al. (2002), J. Immunol. Methods 259, 95-110) (referred to e.g. as K562-A*0201) were used for validation assays. The primary human newborn foreskin fibroblast cell line CCD-1079Sk (ATCC No. CRL-2097) was cultured according to the manufacturers' instructions. The monospecific CTL cell line IVSB specific for the HLA A*0201 restricted tyrosinase-derived epitope Tyr.sub.368-376 (Wolfel, T. et al. (1993), Int. J. Cancer 55, 237-244; Wolfel, T. et al. (1994) Eur. J. Immunol. 24, 759-764) was cultured in AIM-V medium (Invitrogen, Karlsruhe, Germany) with 10% human AB serum (Lonza, Basel, Switzerland), 350 IU/ml IL-2 (Richter-Helm BioLogics, Hamburg, Germany), 5 ng/mL IL-7 (PeproTech, Frankfurt, Germany) and 10 ng/ml IL-15 (R&D Systems, Wiesbaden-Nordenstadt, Germany) and stimulated weekly with irradiated SK29-MeI and AK-EBV cells.
(28) Peripheral blood mononuclear cells (PBMCs), Monocytes and Dendritic Cells (DCs)
(29) PBMCs were isolated by Ficoll-Hypaque (Amersham Biosciences, Uppsala, Sweden) density gradient centrifugation from buffy coats or from blood samples. HLA allelotypes were determined by PCR standard methods. Monocytes were enriched with anti-CD14 microbeads (Miltenyi Biotech, Bergisch-Gladbach, Germany). Immature DCs (iDCs) were obtained by differentiating monocytes for 5 days in cytokine-supplemented culture medium as described in Kreiter et al. (2007), Cancer Immunol. Immunother., CII, 56, 1577-87.
(30) Peptides and Peptide Pulsing of Stimulator Cells
(31) Pools of N- and C-terminally free 15-mer peptides with 11 amino acid overlaps corresponding to sequences of CMV-pp65, HIV-gag, TPTE, NY-ESO-I or PLAC1 (referred to as antigen peptide pool) were synthesized by standard solid phase chemistry (JPT GmbH, Berlin, Germany) and dissolved in DMSO to a final concentration of 0.5 mg/ml. Nonamer peptides were reconstituted in PBS 10% DMSO. For pulsing stimulator cells were incubated for 1 h at 37 C. in culture medium using different peptide concentrations.
(32) Vectors for In Vitro Transcription (IVT) of RNA
(33) All constructs are variants of the previously described pST1-sec-insert-2gUTR-A(120)-Sap1 plasmid (Holtkamp, S. et al. (2006), Blood 108, 4009-4017). To obtain plasmids encoding human TCR chains, cDNA coding for TCR- or TCR-.sub.1 and TCR-.sub.2 constant regions were amplified from human CD8+ T cells and cloned into this backbone. For generation of plasmids encoding murine TCR chains, cDNAs coding for TCR-, -.sub.1 and -.sub.2 constant regions were ordered from a commercial provider and cloned analogously (GenBank accession numbers M14506, M64239 and X67127, respectively). Specific V(D)J PCR products were introduced into such cassettes to yield full-length TCR chains (referred to as pST1-human/murineTCR-2gUTR-A(120)).
(34) Analogously, individual HLA class I and II alleles cloned from PBMCs of donors and beta-2-microgobulin (B2M) cDNA from human DCs were inserted into this backbone (referred to as pST1-HLA class I/II-2gUTR-A(120) and pST1-B2M-2gUTR-A(120)).
(35) Plasmids coding for pp65 antigen of CMV (pST1-sec-pp65-MITD-2gUTR-A(120)) and NY-ESO-I (pST1-sec-NY-ESO-1-MITD-2gUTR-A(120)) linked to a secretion signal (sec) and the MHC class I trafficking signal (MITD) were described previously (Kreiter, S. et al. (2008), J. Immunol. 180, 309-318). PLAC1 encoding plasmid pST1-sec-PLAC1-MITD-2gUTR-A(120) was generated by cloning a cDNA obtained from a commercial provider (GenBank accession number NM_021796) into the Kreiter et al. backbone. TPTE encoding plasmids pST1-gUTR-TPTE-2gUTR-A(120) and pST1-gUTR-TPTE-MITD-2gUTR-A(120) were generated by cloning a cDNA obtained from a commercial provider (GenBank accession number AF007118) into a variant of the Holtkamp et al. vector featuring an additional alpha-globin 5-untranslated region.
(36) Primers were purchased from Operon Biotechnologies, Cologne, Germany.
(37) Generation of In Vitro Transcribed (IVT) RNA and Transfer into Cells
(38) Generation of IVT RNA was performed as described previously (Holtkamp, S. et al. (2006), Blood 108, 4009-4017) and added to cells suspended in X-VIVO 15 medium (Lonza, Basel, Switzerland) in a pre-cooled 4-mm gap sterile electroporation cuvette (Bio-Rad Laboratories GmbH, Munich, Germany). Electroporation was performed with a Gene-Pulser-II apparatus (Bio-Rad Laboratories GmbH, Munich, Germany) (T cells: 450 V/250 F; IVSB T cells: 350 V/200 F; SupT1 (ATCC No. CRL-1942): 300 V/200 F; human DC: 300 V/150 F; K562: 200 V/300 F).
(39) In Vitro Expansion of Antigen-Specific T Cells
(40) 2.510.sup.6 PBMCs/well were seeded in 24-well plates, pulsed with peptide pool and cultured for 1 week in complete culture medium supplemented with 5% AB serum, 10 U/ml IL-2 and 5 ng/ml IL-7. For some experiments CD8+ or CD4+ T cells were purified from PBMC by positive magnetic cell sorting (Miltenyi Biotech, Bergisch-Gladbach, Germany) and then expanded by coculturing of 210.sup.6 effectors with 310.sup.5 autologous DCs either electroporated with antigen-encoding RNA or pulsed with the overlapping peptide pool for 1 week in complete medium supplemented with 5% AB serum, 10 U/ml IL-2, and 5 ng/ml IL-7.
(41) Single-Cell Sorting of Antigen-Specific CD8+ or CD4+ T Cells after IFN Secretion Assay
(42) Flow cytometric sorting of single antigen-specific CD8+ or CD4+ T cells was conducted either directly ex vivo from freshly isolated T cells or PBMC or after one week of antigen-specific expansion. 210.sup.6 T cells or PBMC were stimulated with 310.sup.5 autologous DCs loaded with peptide pool or transfected with IVT RNA encoding the respective antigen or a control antigen for 4 to 15 hours depending on the stimulation mode. Cells were harvested, treated with a Phycoerythrin (PE)-conjugated anti-IFN antibody, a Fluoresceinisothiocyanat (FITC)-conjugated anti-CD8 and an Allophycocyanin (APC)-conjugated anti-CD4 antibody according to the IFN secretion assay kit (Miltenyi Biotech, Bergisch-Gladbach, Germany). Sorting was conducted on a BD FACS Aria flow cytometer (BD Biosciences, Heidelberg, Germany). Cells double-positive for IFN and CD8 or CD4 were sorted and one cell per well was harvested in a 96-well V-bottom-plate (Greiner Bio-One GmbH, Solingen, Germany) containing NIH3T3 mouse fibroblasts as feeder cells, centrifuged at 4 C. and stored immediately at 80 C.
(43) In Vivo Priming of T Cells by Intranodal Immunization of HLA A2.1/DR1 Mice with IVT RNA
(44) T cells of A2.1/DR1 mice (Pajot A. et al. (2004), Eur. J. Immunol. 34, 3060-69) were primed in vivo against the antigen of interest by repetitive intranodal immunization using antigen-encoding IVT RNA (Kreiter S. et al. (2010), Cancer Research 70, 9031-40). For intranodal immunizations, mice were anesthetized with xylazine/ketamine. The inguinal lymph node was surgically exposed, 10 L, RNA (20 g) diluted in Ringer's solution and Rnase-free water were injected slowly using a single-use 0.3-ml syringe with an ultrafine needle (31G, BD Biosciences), and the wound was closed. After six immunization cycles the mice were sacrificed and spleen cells were isolated.
(45) Harvest of Spleen Cells
(46) Following their dissection under sterile conditions, the spleens were transferred to PBS containing falcon tubes. The spleens were mechanically disrupted with forceps and the cell suspensions were obtained with a cell strainer (40 m). The splenocytes were washed with PBS centrifuged and resuspended in a hypotonic buffer for lysis of the erythrocytes. After 5 min incubation at RT, the reaction was stopped by adding 20-30 ml medium or PBS. The spleen cells were centrifuged and washed twice with PBS.
(47) Single-Cell Sorting of Antigen-Specific CD8+ T Cells after CD137 Staining
(48) For antigen-specific restimulation 2.510^6/well spleen cells from immunized A2.1/DR1 mice were seeded in a 24-well plate and pulsed with a pool of overlapping peptides encoding the antigen of interest or a control antigen. After 24 h incubation cells were harvested, stained with a FITC-conjugated anti-CD3 antibody, a PE-conjugated anti-CD4 antibody, a PerCP-Cy5.5-conjugated anti-CD8 antibody and a Dylight-649-conjugated anti-CD137 antibody. Sorting was conducted on a BD FACS Aria flow cytometer (BD Biosciences). Cells positive for CD137, CD3 and CD8 or CD4 were sorted, one cell per well was harvested in a 96-well V-bottom-plate (Greiner Bio-One) containing human CCD-1079Sk cells as feeder cells, centrifuged at 4 C. and stored immediately at 80 C.
(49) RNA Extraction, SMART-Based cDNA Synthesis and Unspecific Amplification from Sorted Cells
(50) RNA from sorted T cells was extracted with the RNeasy Micro Kit (Qiagen, Hilden, Germany) according to the instructions of the supplier. A modified BD SMART protocol was used for cDNA synthesis: BD PowerScript Reverse Transcriptase (BD Clontech, Mountain View, Calif.) was combined with oligo(dT)-T-primer long for priming of the first-strand synthesis reaction and TS-short (Eurogentec S. A., Seraing, Belgium) introducing an oligo(riboG) sequence to allow for creation of an extended template by the terminal transferase activity of the reverse transcriptase and for template switch (Matz, M. et al. (1999) Nucleic Acids Res. 27, 1558-1560). First strand cDNA synthesized according to the manufacturer's instructions was subjected to 21 cycles of amplification with 5 U PfuUltra Hotstart High-Fidelity DNA Polymerase (Stratagene, La Jolla, Calif.) and 0.48 M primer TS-PCR primer in the presence of 200 M dNTP (cycling conditions: 2 min at 95 C. for, 30 s at 94 C., 30 s at 65 C., 1 min at 72 C. for, final extension of 6 min at 72 C.). Successful amplification of TCR genes was controlled with either human or murine TCR- constant region specific primers and consecutive clonotype-specific human or murine V-/V-PCRs were only performed if strong bands were detected.
(51) First strand cDNA for the amplification of HLA class I or II sequences was synthesized with SuperScriptII Reverse Transcriptase (Invitrogen) and Oligo(dT) primer with 1-5 jag RNA extracted from patient-derived PBMCs.
(52) Design of PCR Primers for TCR and HLA Amplification
(53) For design of human TCR consensus primers, all 67 TCR-V and 54 TCR-V genes (open reading frames and pseudogenes) as listed in the ImMunoGeneTics (IMGT) database (http://www.imgt.org) together with their corresponding leader sequences were aligned with the BioEdit Sequence Alignment Editor (e.g. http://www.bio-soft.net). Forward primers of 24 to 27 bp length with a maximum of 3 degenerated bases, a GC-content between 40-60% and a G or C at the 3 end were designed to anneal to as many leader sequences as possible and equipped with a 15 bp 5 extension featuring a rare restriction enzyme site and Kozak sequence. Reverse primers were designed to anneal to the first exons of the constant region genes, with primer TRACex1_as binding to sequences corresponding to amino acids 7 to 16 of C and TRBCex1_as to amino acids (aa) 8 to 16 in C1 and C2. Both oligonucleotides were synthesized with a 5 phosphate. Primers were bundled in pools of 2-5 forward oligos with identical annealing temperature.
(54) This strategy was replicated for the design of murine TCR consensus primers, aligning 129 listed TCR-V and 35 listed TCR-V genes. Reverse primers mTRACex1_as and mTRBCex1_as are homologous to sequences corresponding to aa 24 to 31 and 8 to 15, respectively.
(55) HLA consensus primers were designed by aligning all HLA class I and II sequences listed on the Anthony Nolan Research Institute website (www.anthonynolan.com) with the BioEdit Sequence Alignment Editor. Forward primers of 23 to 27 bp length with a maximum of 3 degenerated but code-preserving bases annealing to as many as possible HLA sequences of one locus were equipped with a 5-phosphate and Kozak sequence extension. Reverse primers were designed analogously but without introduction of wobble bases and equipped with a 14 bp 5-extension encoding an AsiSI restriction enzyme site.
(56) PCR Amplification and Cloning of V(D)J and HLA Sequences
(57) 3-6 l of preamplified cDNA from isolated T cells was subjected to 40 cycles of PCR in the presence of 0.6 M V-/V-specific oligo pool, 0.6 M C- or C-oligo, 200 M dNTP and 5 U Pfu polymerase (cycling conditions: 2 min at 95 C., 30 s at 94 C., 30 s annealing temperature, 1 min at 72 C., final extension time of 6 min at 72 C.). PCR products were analyzed using Qiagen's capillary electrophoresis system. Samples with bands at 400-500 bp were size fractioned on agarose gels, the bands excised and purified using a Gel Extraction Kit (Qiagen, Hilden, Germany). Sequence analysis was performed to reveal the sequence of both the V(D)J domain and 3 constant region, as TRBCex1_as and mTRBCex1_as primer, respectively, match to both TCR constant region genes 1 and 2 in human and mouse, respectively. DNA was digested and cloned into the IVT vectors containing the appropriate backbone for a complete TCR-/ chain.
(58) HLA sequences were amplified according to the manufacturer's instructions with 2.5 U Pfu polymerase from donor specific cDNA using specific HLA class I or II sense and antisense primers. As transcription of DRB3 genes is at least five fold lower than that of DRB1 genes (Berdoz, J. et al. (1987) J. Immunol. 139, 1336-1341), amplification of DRB3 genes was conducted in two steps using a nested PCR approach. PCR fragments were purified, AsiSI-digested and cloned into the EcoRV- and AsiSJ-digested IVT vector. EciI- or SapI-sites within the inserts were mutated using QuikChange Site-Directed Mutagenesis Kits (Stratagene, La Jolla, Calif.).
(59) Flow Cytometric Analyses
(60) Cell surface expression of transfected TCR genes was analyzed by flow cytometry using PE-conjugated anti-TCR antibody against the appropriate variable region family or the constant region of the TCR chain (Beckman Coulter Inc., Fullerton, USA) and FITC-/APC-labeled anti-CD8/-CD4 antibodies (BD Biosciences). HLA antigens were detected by staining with FITC-labeled HLA class II-specific (Beckman Coulter Inc., Fullerton, USA) and PE-labeled HLA class I-specific antibodies (BD Biosciences). Flow cytometric analysis was performed on a FACS Calibur analytical flow cytometer using Cellquest-Pro software (BD Biosciences).
(61) Luciferase Cytotoxicity Assay
(62) For assessment of cell-mediated cytotoxicity a bioluminescence-based assay was established as an alternative and optimization to .sup.51Cr release. In contrast to the standard chromium release assay, this assay measures lytic activity of effector cells by calculating the number of viable luciferase expressing target cells following coincubation. The target cells were stably or transiently transfected with the luciferase gene coding for the firefly luciferase from firefly Photinus pyralis (EC 1.13.12.7). Luciferase is an enzyme catalyzing the oxidation of luciferin. The reaction is ATP-dependent and takes place in two steps:
luciferin+ATP.fwdarw.luciferyl adenylate+PP.sub.i
luciferyl adenylate+O.sub.2.fwdarw.oxyluciferin+AMP+light
Target cells were plated at a concentration of 10.sup.4 cells per well in white 96-well plates (Nunc, Wiesbaden, Germany) and were cocultivated with varying numbers of TCR-transfected T cells in a final volume of 100 l 3 h later 50 l of a D-Luciferin (BD Biosciences) containing reaction mix (Luciferin (1 g/l), HEPES-buffer (50 mM, pH), Adenosine 5-triphosphatase (ATPase, 0.4 mU/l, Sigma-Aldrich, St. Louis, USA) was added to the cells. By addition of ATPase to the reaction mix luminescence resulting from luciferase released from dead cells was diminished.
(63) After a total incubation time of 4 h bioluminescence emitted by viable cells was measured using the Tecan Infinite 200 reader (Tecan, Crailsheim, Germany). Cell-killing activity was calculated in regard to luminescence values obtained after complete cell lysis induced by the addition of 2% Triton-X 100 and in relationship to luminescence emitted by target cells alone. Data output was in counts per second (CPS) and percent specific lysis was calculated as follows:
(1(CPS.sub.expCPS.sub.min)/(CPS.sub.maxCPS.sub.min)))*100.
(64) Maximum luminescence (maximum counts per second, CPSmax) was assessed after incubating target cells without effectors and minimal luminescences (CPSmin) was assessed after treatment of targets with detergent Triton-X-100 for complete lysis.
(65) ELISPOT (Enzyme-Linked ImmunoSPOT Assay)
(66) Microtiter plates (Millipore, Bedford, Mass., USA) were coated overnight at room temperature with an anti-IFN antibody 1-D1k (Mabtech, Stockholm, Sweden) and blocked with 2% human albumin (CSL Behring, Marburg, Germany). 2510.sup.4/well antigen presenting stimulator cells were plated in triplicates together with 0.3310.sup.5/well TCR-transfected CD4+ or CD8+ effector cells 24 h after electroporation. The plates were incubated overnight (37 C., 5% CO.sub.2), washed with PBS 0.05% Tween 20, and incubated for 2 hours with the anti-IFN biotinylated mAB 7-B6-1 (Mabtech) at a final concentration of 1 g/ml at 37 C. Avidin-bound horseradish peroxidase H (Vectastain Elite Kit; Vector Laboratories, Burlingame, USA) was added to the wells, incubated for 1 hour at room temperature and developed with 3-amino-9-ethyl carbazole (Sigma, Deisenhofen, Germany).
Example 2
Isolation of TCRs Specific for the Viral Antigen CMV-Pp 65
(67) The TCR isolation/validation protocol (
(68) The viral tegument protein pp65 is one of the major targets of CMV-specific cytotoxic T lymphocytes, which are present in high frequencies in the peripheral blood of non-immunocompromised seropositive individuals (Kern, F. et al. (1999), J. Virol. 73, 8179-8184; Wills, M. R. et al. (1996), J. Virol. 70, 7569-7579; Laughlin-Taylor, E. et al. (1994), J. Med. Virol. 43, 103-110).
(69) CMV-pp65-specific IFN secreting CD8+ T cells of a seropositive healthy donor were isolated by flow cytometry after one week of antigen-specific expansion and rechallenge with autologous DCs transfected with IVT RNA encoding the whole pp65 antigen (
(70) TCR / variable regions were amplified from single T cells using a set of sequence-specific, partially degenerated oligonucleotides. Amplification products were cloned site-directed into vectors containing the TCR / constant regions providing full-length templates for instant in vitro transcription (
(71) For verification of cell surface expression TCR / RNAs were transferred into SupT1 cells otherwise lacking expression of endogenous TCR chains and analyzed by flow cytometry (
(72) For functional validation of cloned TCRs, the monospecific T cell line IVSB recognizing the tyrosinase-derived epitope Tyr.sub.368-376 (Wolfel T. et al. (1994), Eur. J. Immunol. 24, 759-64) was transfected with TCR RNA and analyzed for specific cytokine secretion in response to pp65 antigen by IFN-ELISPOT (
(73) To determine the HLA restricting element, IVSB cells transfected with TCR.sub.CD8-CMV#1 were analyzed for specific IFN secretion after co-culture with peptide-pulsed K562 cells expressing selected HLA alleles of the patient (
(74) After successful isolation of TCRs from pp65-specific CD8+ T cells expanded in vitro to a high frequency, the TCR isolation protocol was applied to ex vivo sorted T cells present with lower frequencies.
(75) CD8+ T cells magnetically purified from PBMCs of an HLA A*0201 positive donor were stimulated with autologous target cells pulsed with the immunodominant HLA A*0201-restricted epitope pp65.sub.495-563 and activated IFN secreting T cells were sorted by flow cytometry.
(76) Specificity of TCRs obtained ex vivo from the CD8+ T cells after presentation with pp65.sub.495-503 was analyzed in an IFN-ELISPOT assay. As shown in
(77) In order to show that cloned pp65-specific TCRs are also able to mediate cytolytic effector function a luciferase-based cytotoxicity assay was conducted using IVSB cells transfected with TCR.sub.CD8-CMV#1 or TCR.sub.CD8-CMV#14.
(78) Specific killing of appropriate target cells (K562-B*3501 cells pulsed with pp65.sub.117-131 and K562-A*0201 cells pulsed with peptide pp65.sub.495-503, respectively) was compared to the killing of Tyr.sub.368-376-pulsed K562-A*0201 cells mediated by the endogenous TCR of IVSB effectors (
(79) Titration of the effector-to-target (E:T) ratio confirmed that target cells pulsed with the appropriate pp65 peptide were specifically lysed by TCR-transfected IVSB cells. Up to 85% of target cells were killed by IVSB cells transfected with TCR.sub.CD8-CMV#1 and TCR.sub.CD8-CMV#14, respectively. Remarkably, recombinant TCRs mediated equally efficient lysis as the natural TCR at a broad range of E:T ratios.
(80) In summary, 13 hCMV-pp65-specific TCRs were isolated from CD4+ and CD8+ T cells obtained from four different CMV seropositive donors either ex vivo or after antigen-specific expansion as listed in Table 1.
Example 3
Isolation of TCRs Specific for the Tumor Antigen NY-ESO-1
(81) After proof of concept studies using CMV-pp65 as a viral model antigen eliciting high frequencies of antigen-specific T cells, we evaluated the capability of our approach to clone TCRs from tumor antigen-specific T cell populations of low abundance. Frequencies of pre-existing T cells against tumor-associated self proteins are generally much lower than frequencies of T cells elicited by persisting viruses. For application of our method to the tumor setting we resorted to the highly immunogenic tumor antigen NY-ESO-1.
(82) NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells. NY-ESO-1 (synonyms: CTG. CTAG, CTAG1, ESO1, LAGE-2, LAGE2, LAGE2A, LAGE2B, OTTHUMP00000026025, OTTHUMP00000026042) is one of the best characterized cancer testis antigens identified by SEREX (Chen, Y. T. et al. (1997), Proc. Natl. Acad. Sci. U.S.A 94, 1914-1918), which is expressed in a variety of malignant neoplasms, including melanomas, esophageal, breast, prostate, urinary tract, ovarian and lung cancers (Chen, Y. T. et al. (1997) Proc. Natl. Acad. Sci. U.S.A 94, 1914-1918; Jungbluth, A. A. et al. (2001) Int. J. Cancer 92, 856-860; Schultz-Thater, E. et al. (2000) Br. J. Cancer 83, 204-208). Due to its natural immunogenicity it is favored as a model antigen for tumor vaccination strategies. NY-ESO-1 frequently elicits high-titer antibody responses in patients bearing NY-ESO-1 expressing tumors and it was shown that autoantibody responses against NY-ESO-1 are often associated with the presence of antigen-specific CD8+ and CD4+ T cells (Zeng, G. et al. (2001), Proc. Natl. Acad. Sci. U.S.A 98, 3964-3969; Jager, E. et al. (1998), J. Exp. Med. 187, 265-270; Gnjatic, S. et al. (2003), Proc. Natl. Acad. Sci. U.S.A 100, 8862-8867; Valmori, D. et al. (2007), Clin. Immunol. 122, 163-172).
(83) We selected a NSCLC patient based on his autoantibody reactivity against NY-ESO-1, pulsed his bulk PBMCs with NY-ESO-1 peptide pool and expanded for one week. After exposure to autologous NY-ESO-1 RNA transfected DCs IFN secreting CD8+ T cells were sorted and TCRs were cloned from single cells. Validation of identified TCRs for specific recognition of NY-ESO-1 expressing target cells by IFN ELISPOT assay resulted in seven functional NY-ESO-1-specific TCRs obtained from this patient. As shown in
(84) HLA restrictions of NY-ESO-1-specific TCRs were determined by IFN-ELISPOT using TCR-transfected IVSB effectors co-cultured with K562 cells expressing individual HLA class I alleles of the patient and pulsed with NY-ESO-1 peptide pool. A representative result is shown in
(85) For epitope mapping IVSB T cells were transfected with NY-ESO-1-specific TCRs and co-cultured with K562 cells expressing the appropriate HLA antigen pulsed with individual overlapping 15mer peptides spanning the NY-ESO-1 protein. Reactivity of TCR-transfected T cells against the NY-ESO-1 peptides was assayed in IFN-ELISPOT assays (
(86) Remarkably, epitopes of all seven TCRs were localized to amino acids 85-111 of the NY-ESO-1 protein (
(87) In order to show that NY-ESO-1-specific TCRs isolated from CD8+ T cells are able to mediate cytolytic effector functions, TCR-transgenic IVSB cells were analyzed for specific killing of peptide-pulsed K562-A*6801 cells. As shown in
(88) Validation of TCRs isolated from CD4+ T cells of two other seropositive NSCLC patients resulted in cloning of 9 independent functional NY-ESO-1-specific TCRs. Determination of restriction elements (
(89) To date, 16 NY-ESO-1-specific TCRs were cloned from CD4+ and CD8+ derived from three different NSCLC patients and characterized regarding HLA restriction and peptide specificity (Table 2).
Example 4
Isolation of TCRs Specific for the Tumor Antigen TPTE
(90) TPTE (Transmembrane Phosphatase with Tensin homology; synonyms: CT44, PTEN2, EC 3.1.3.48, OTTHUMP00000082790), is a sperm cell-specific lipid phosphatase that is aberrantly transcribed in many human cancers (Chen, H. et al. (1999), Hum. Genet. 105, 399-409; Dong, X. Y. et al. (2003), Br. J. Cancer 89, 291-297; Singh, A. P. et al. (2008), Cancer Lett. 259, 28-38), but little is known about its immunogenicity and T cell responses had not been reported so far.
(91) In order to isolate TPTE-specific TCRs, 3 NSCLC patients showing significant absorbance values in the pre-screening by CrELISA were selected for antigen-specific expansion and flow cytometry sorting of TPTE-specific CD8+ and CD4+ T cells.
(92) TCRs isolated from CD8+ T cells were validated for recognition of TPTE expressing target cells and were characterized regarding HLA restriction and epitope specificity as exemplarily shown for TCR.sub.CD8TPT#3 in
(93) Analogously, TCRs isolated from CD4+ T cells were validated for specific recognition of K562 cells expressing TPTE and individual HLA class II alleles of the donor (
(94) A total of 31 functional TPTE-reactive TCRs were identified thus far, from which two are derived from CD8+ cells and 29 are derived from CD4+ T cells of three different NSCLC patients (Table 3). Fine mapping of epitopes by the use of single-peptide-pulsed HLA allele-expressing K562 target cells, disclosed that epitopes were distributed all over the TPTE protein sequence (Table 5).
Example 5
Isolation of High-Affinity PLAC1-Specific TCRs from T Cells of Immunized A2.1/DR1 Mice
(95) The trophoblast-specific gene PLAC1 (PLACenta-specific 1, synonyms: OTTHUMP00000024066; cancer/testis antigen 92) is a novel member of cancer-associated placental genes (Koslowski M. et al. (2007), Cancer Research 67, 9528-34). PLAC1 is ectopically expressed in a wide range of human malignancies, most frequently in breast cancer, and is essentially involved in cancer cell proliferation, migration, and invasion. In order to obtain TCRs specific for PLAC1, we changed the source for antigen-specific T cells. As TCRs isolated from the natural repertoire of cancer patients are usually of low affinity owing to central tolerance mechanisms, we applied an alternative approach bypassing tolerance to generate high-affinity T cells specific for PLAC1. T cells of HLA A2.1/DR1 transgenic mice (Pajot A. et al. (2004), Eur. J. Immunol. 34, 3060-69) were primed in vivo against the human PLAC1 antigen by repetitive intranodal immunization using PLAC1-encoding IVT RNA (Kreiter S. et al. (2010), Cancer Research 70, 9031-40). Spleen cells obtained from these mice were rechallenged with PLAC1 overlapping peptides following detection and isolation of antigen-specific T cells based on their activation-induced upregulation of CD137 (
(96) For validation of TCRs cloned from murine CD8+ T cells TCR-engineered IVSB cells were analyzed for specific cytokine secretion in response to PLAC1 peptide-pulsed K562-A*0201 cells by IFN-ELISPOT (
(97) By cloning of 11 PLAC1-specific TCRs (Table 4) and identification of two HLA A*0201-presented immunodominant PLAC1 epitopes (Table 5) we could show that T cells of A2/DR1 mice primed in vivo by intranodal vaccination with antigen-encoding IVT RNA are exploitable as a source for TCR isolation.
CONCLUSION
(98) We were able to establish a versatile platform technology for efficient cloning and rapid characterization of immunologically relevant TCRs from small antigen-specific T cell populations without the need for generation of T cell clones or lines and prior knowledge of restriction elements or T cell epitopes.
(99) Usage of our TCR isolation/validation approach for viral and tumor antigens resulted in the discovery of more than 70 antigen-specific TCRs (Table 1, 2, 3, 4), whereof far more than half were directed against novel HLA presented epitopes (Table 5).
(100) Notably, from single donors several TCR specificities derived from CD8+ as well as CD4+ T lymphocytes were cloned in parallel and shown to reprogram T cell effectors for recognition of the respective antigen.
(101) This approach enables the generation of a large library of TCRs in a timely manner for off the shelf use filling the gap between the availability of a large amount of target structures and the small number of suitable TCR candidates for antigen-specific therapy approaches in the field of cancer, autoimmunity and infectious diseases.
TABLES
(102) TABLE-US-00001 TABLE 1 hCMV pp65-specific TCRs HLA class I/II Recognized Designation TCR alpha chain.sup.a TCR beta chain.sup.a restriction .sup.b region TCR.sub.CD8-CMV#1 V1.2 J24_2 C V3.1 D2 J2.1 C2 B*3501 aa 117-139, best 117-131 TCR.sub.CD8-CMV#4 V3 J43 C V6.5 D1 J1.2 C1 A*0201 aa 495-503 TCR.sub.CD8-CMV#8 V22 J58 C V10.1 D J1.4 C1 A*0201 aa 495-503 TCR.sub.CD8-CMV#9 V19 J26 C V13 D2 J2.1 C2 pending pending TCR.sub.CD8-CMV#10 V24 J49 C V6.5 D1 J1.2 C1 A*0201 aa 495-503 TCR.sub.CD8-CMV#11 V16 J36 C V25.1 D1 J2.2 C2 A*0201 aa 495-503 TCR.sub.CD8-CMV#12 V39 J58 C V9 D2 J2.2 C2 A*0201 aa 495-503 TCR.sub.CD8-CMV#14 V24 J21 C V3.1 D2 J2.2 C2 A*0201 aa 495-503 TCR.sub.CD8-CMV#15 V12.3 J43 C V12.4 D1 J1.4 C1.sup.c A*0201 aa 495-503 TCR.sub.CD8-CMV#16 V13.1_2 J50 C V25.1 J1.3 C1 A*0201 aa 495-503 TCR.sub.CD4-CMV#1 V21 J43 C V3.1 D1 J1.1 C1 DRB1*0701 aa 117-139 TCR.sub.CD4-CMV#3 V8.6_2 J37_2 C V6.1 D1 J1.2 C1 DRB1*0701 aa 337-359 TCR.sub.CD4-CMV#5 V22 J49 C V6.2 D2 J2.3 C2.sup.d DRB1*0701 aa 337-359
(103) TABLE-US-00002 TABLE 2 NY-ESO-1-specific TCRs HLA class I/II Recognized Designation TCR alpha chains.sup.a TCR beta chain.sup.a restriction.sup.b region TCR.sub.CD8-NY#2 V3 J28 C V20.1_2 J2.3 C2 A*6801 aa 93-107 TCR.sub.CD8-NY#5 V24 J3 C V7.6 D2 J2.2 C2 B*3508 aa 92-100 TCR.sub.CD8-NY#6 V17 J47_2 C V12.3 D2 J2.1 C2 B*3508 aa 92-100 TCR.sub.CD8-NY#8 V8.6_2 J9 C V28.1 D1 J1.1 C1 B*3508 aa 92-100 TCR.sub.CD8-NY#12 V1.1 J23 C V4.1 D2 J2.1 C2 B*0702 aa 97-111 TCR.sub.CD8-NY#13 V5 J33 C V5.5_2 D1 J2.5 C2 A*6801 aa 93-107 TCR.sub.CD8-NY#15 V12.2_2 J53 C V4.1 D2 J2.5 C2 B*3508 aa 92-100 TCR.sub.CD4-NY#1 V22 J20 C V9 D1 J1.1 C1 DRB1*0401 aa 165-180 TCR.sub.CD4-NY#3 V12.3 J54 C V11.2 D2 J2.2 C2 DRB1*0401 aa 117-139 TCR.sub.CD4-NY#5 V8.4_3 J48 C V4.1 D1 J1.5 C1 DRB1*1101 aa 117-139 TCR.sub.CD4-NY#7 V8.6_2 J13_2 C V20.1 D2 J2.5 C2 DRB1*1101 aa 117-139 DRB1*1601 TCR.sub.CD4-NY#10 V9.2_3 J42 C V7.9_3 D2 J2.7 C2 DRB5*0202 aa 85-99 TCR.sub.CD4-NY#11 V8.1 J23 C V11.2 D1 J1.2 C1 DRB1*1101 aa 117-139 TCR.sub.CD4-NY#13 V21_2 J24_2 C V7.9_3 D1 J2.3 C2 DRB5*0202 aa 129-147 TCR.sub.CD4-NY#16 V8.4_3 J10 C V20.1 D1 J1.5 C1 DRB3*0201 aa 117-139 TCR.sub.CD4-NY#14 V8.4_3 J37_2 C V3.1 D2 J1.3 C1 DRB3*0201 aa 121-135
(104) TABLE-US-00003 TABLE 3 TPTE-specific TCRs HLA class I/II Recognized Designation TCR alpha chain.sup.a TCR beta chain.sup.a restriction.sup.b region TCR.sub.CD8-TPT#3 V27 J16 C V7.9 D2 J2.2 C2 B*3501 aa 527-535 TCR.sub.CD8-TPT#35 V19 J17 C V6.2/V6.3 D1 J1.2 B*0702 aa 188-196 C1.sup.d TCR.sub.CD4-TPT#4 V14/DV4 J48 C V29.1 D1 J1.2 C1 DRB4*0101 aa 405-423 TCR.sub.CD4-TPT#5 V38.2/DV8 J40 C V4.2 D2 J2.7 C2 DRB1*1401 aa 417-435 TCR.sub.CD4-TPT#6 V12.3 J35 C V5.4 D1 J1.3 C1 DRB1*1401 aa 53-71 TCR.sub.CD4-TPT#8 V38.1 J45 C V3.1 D1 J2.7 C2 DRB3*0201/2 aa 181-195 TCR.sub.CD4-TPT#11 V17 J27 C V6.6_ 2 D1 J2.3 C2 DRB1*0701 aa 109-127 TCR.sub.CD4-TPT#13 V20_2 J29 C V19 D2 J2.1 C2 DRB1*1401 aa 497-515 TCR.sub.CD4-TPT#17 V29/DV5 J49 C V7.2 D1 J2.7 C2 DRB5*0202 aa 177-195 TCR.sub.CD4-TPT#27 V13.1_ 2 J45 C V19 D1 J1.1 C1 DRB3*0301 aa 181-195 TCR.sub.CD4-TPT#33 V29/DV5 J42 C V24.1 D2 J2.1 C2 DRB5*0202 aa 217-231 TCR.sub.CD4-TPT#38 V39 J18 C V5.5_2 D1 J1.4 C1 DRB1*1601 aa 277-291 TCR.sub.CD4-TPT#42 V25 J10 C V7.8 D2 J2.7 C2 DRB1*1301 aa 269-283 TCR.sub.CD4-TPT#45 V13.2 J23 C V20.1 D1 J1.2 C1 DRB1*1501 aa 413-427 TCR.sub.CD4-TPT#48 V8.3 J43 C V28 D1 J1.1 C1 DRB1*1501 aa 173-187 TCR.sub.CD4-TPT#49 V38.1 J49 C V19 D2 J2.2 C2 DRB1*1501 aa 393-411 TCR.sub.CD4-TPT#51 V13.1_2 J53 C V14 D1 J1.1 C1 DRB1*1301 aa 217-231 TCR.sub.CD4-TPT#52 V8.3 J54 C V6.1 D2 J2.7 C2 DRB1*1501 aa 117-135 TCR.sub.CD4-TPT#54.sup.g V9.2 J23 C V20.1 D1 J1.1 C1 DQB1*0602/03; aa 53-67 DQA*0102/03 aa 77-91 aa 245-259 TCR.sub.CD4-TPT#55 V38.2/DV8 J34 C V5.1 J2.1 C2 DRB1*1301 aa 177-195 TCR.sub.CD4-TPT#57 V8.1 J27 C V5.1 D2 J2.7 C2 DRB1*1501 aa 81-95 TCR.sub.CD4-TPT#59 V39 J49 C V7.9_3 D2 J2.4 C2 DRB1*1301 aa 141-155 TCR.sub.CD4-TPT#67 V12.3 J9 C V5.1 D2 J2.7 C2 DRB1*1501 aa 173-187 TCR.sub.CD4-TPT#76 V8.3 J57 C V19 D2_2 J2.7 C2 DQA1*0102/DQB1*0602 aa 453-467 DQA1*0103/DQB1*0602 DQA1*0103/DQB1*0603 TCR.sub.CD4-TPT#77 V14/DV4_3 J50 C V20.1 D2 J2.2 C2 DRB1*1301 aa 417-435 TCR.sub.CD4-TPT#78 V8.6_2 J21 C V2 D1 J1.6_2 C1 DRB1*1301 aa 221-235 TCR.sub.CD4-TPT#79.sup.g V38.2/DV8 J39 C V5.1 D2 J2.1 C2 DRB1*1501 aa 149-163 aa 157-171 aa 173-187 TCR.sub.CD4-TPT#82 V38.2/DV8 J39 C V19 D1 J2.7 C2 DRB1*1301 aa 409-423 TCR.sub.CD4-TPT#87 V39 J31 C V5.1 J2.6 C2 DRB1*1301 aa 177-195 TCR.sub.CD4-TPT#91 V20_2 J53 C V6.1 D1 J2.7 C2 DRB1*1501 aa 173-187 TCR.sub.CD4-TPT#9.sup.g V23/DV6 J49 C V3.1 D1 J1.2 C1 DRB1*0701 aa 121-135 aa 145-159
(105) TABLE-US-00004 TABLE 4 PLAC1-specific TCRs HLA class I/II Recognized Designation TCR alpha chain.sup.a TCR beta chain.sup.a restriction.sup.b region TCR.sub.CD8-mPl#2 V6D.6_5 J33 C V2 D1 J1.3 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#8 V9D.1 J12 C.sup.e V5 D2 J2.1 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#9 V4D.4_2 J44 C V2 D2 J2.7 C2 A*0201 aa 25-43 TCR.sub.CD8-mPl#11 V6D.6_2 J9_2 C V2 D1 J1.3 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#12 V4D.4_2 J27 C V30 D1 J2.2 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#14 V9D.1_2 J12 C V5 D1 J1.1 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#17 V14.1 J31 C.sup.f V13.2 D2 J2.1 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#19 V6D.3 J22 C V13.3 D1 J1.6 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#20 V12.3_3 J38 C V5 D2 J1.1 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#22 V13D.2 J34_2 C V20 D1 J2.1 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mPl#25 V8.1_3 J21 C V31 D2 J2.1 C2 A*0201 aa 25-43 .sup.aDesignations of the TCR V(D)J genes according to the IMGT nomenclature; Example: V7.9 is the ninth gene of V gene subgroup 7, while V7.9_3 is the third allele of gene 9 of subgroup 7. Alleles are only specified by an underline, if they differ from allele 1. .sup.bDesignations of the HLA alleles begin with HLA- and the locus name, then * and a number of digits specifying the allele. The first two digits specify a group of alleles. The third through fourth digits specify a synonymous allele. Digits five through six denote any synonymous mutations within the coding frame of the gene. The seventh and eighth digits distinguish mutations outside the coding region .sup.cThe TCR beta gene is V12.4_1 or V12.4_2 .sup.dThe TCR beta gene is V6.2 or V6.3 .sup.eThe TCR alpha gene is V9D.1_1 or V9D.1_2 .sup.fThe TCR alpha gene is J31_1 or J31_2 .sup.gPromiscous TCRs recognizing more than one epitope aa = amino acids
(106) TABLE-US-00005 TABLE5 TcellepitopesderivedfromtheantigenshCMVpp65,NY-ESO-I,TPTE,PLAC1 HLAclassI/II SEQID Antigen Epitope Aminoacidsequence restriction NO: hCMVpp65 aa117-139, PLKMLNIPSINVHHYPSAAERKH B*3501 108 best117-131 aa495-503 NLVPMVATV A*0201 109 aa117-139 PLKMLNIPSINVHHYPSAAERKH DRB1*0701 108 aa337-359 VELRQYDPVAALFFFDIDLLLQR DRB1*0701 110 NY-ESO-I aa92-100 LAMPFATPM B*3508 111 aa93-107 AMPFATPMEAELARR A*6801 112 aa97-111 ATPMEAELARRSLAQ B*0702 113 aa85-99 SRLLEFYLAMPFATP DRB5*0202 114 aa117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*0401 115 aa117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*1101 115 aa117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*1601 115 aa117-139 PVPGVLLKEFTVSGNILTIRLTA DRB3*0201 115 aa129-147 SGNILTIRLTAADHRQLQL DRB5*0202 116 aa165-180 CFLPVFLAQPPSGQRR DRB1*0401 117 aa121-135 VLLKEFTVSGNILTI DRB3*0201 175 TPTE aa185-199 RNIPRWTHLLRLLRL B*0702 118 aa527-535 YPSDFAVEI B*3501 119 aa53-71 SPISESVLARLSKFEVEDA DRB1*1401 120 aa81-95 IKKIVHSIVSSFAFG DRB1*1501 121 aa109-127 ILADLIFTDSKLYIPLEYR DRB1*0701 122 aa117-135 DSKLYIPLEYRSISLAIAL DRB1*1501 123 aa141-155 VLLRVFVERRQQYFS DRB1*1301 124 aa173-187 DVVYIFFDIKLLRNI DRB1*1501 125 aa177-191 IFFDIKLLRNLPRWT DRB1*1501 126 aa177-195 IFFDIKLLRNIPRWTHLLR DRB1*1301 127 aa177-195 IFFDIKLLRNIPRWTHLLR DRB5*0202 127 aa181-195 IKLLRNIPRWTHLLR DRB3*0201/2 128 aa181-195 IKLLRNIPRWTHLLR DRB3*0301 128 aa217-231 KLIRRRVSENKRRYT DRB1*1301 129 aa217-231 KLIRRRVSENKRRYT DRB5*0202 129 aa221-235 RRVSENKRRYTRDGF DRB1*1301 130 aa269-283 RFLDKKHRNHYRVYN DRB1*1301 131 aa277-291 NHYRVYNLCSERAYD DRB1*1601 132 aa393-411 YVAYFAQVKHLYNWNLPPR DRB1*1501 133 aa405-423 NWNLPPRRILFIKHFIIYS DRB4*0101 134 aa409-423 PPRRILFIKHFIIYS DRB1*1301 135 aa413-427 ILFIKHFIIYSIPRY DRB1*1501 136 aa417-435 KHFIIYSIPRYVRDLKIQI DRB1*1301 137 aa417-435 KHFIIYSIPRYVRDLKIQI DRB1*1401 137 aa453-467 VLDNITTDKILIDVF DQA1*0102/B1*0602 138 aa453-467 VLDNITTDKILIDVF DQA1*0103/B1*0602 138 aa453-467 VLDNITTDKILIDVF DQA1*0103/B1*0603 138 aa497-515 WLHTSFIENNRLYLPKNEL DRB1*1401 139 aa102-110 VLLDVTLIL A*0201 178 aa164-172 AIIVILLLV A*0201 179 aa188-196 PRWTHLLRL B*0702 180 aa53-67 SPISESVLARLSKFE DQA1*0102/DQB1*0602 181 aa77-91 YDSKIKKIVHSIVSS DQA1*0102/DQB1*0602 182 aa121-135 YIPLEYRSISLAIAL DRB1*0701 183 aa145-159 VFVERRQQYFSDLFN DRB1*0701 184 aa149-163 RRQQYFSDLFNILDT DRB1*1501 185 aa157-171 LFNILDTAIIVILLL DRB1*1501 186 aa245-259 RIIAMSFPSSGRQSF DQA1*0102/DQB1*0602 187 PLAC1 aa28-36 VLCSIDWFM A*0201 172 aa30-41, CSIDWFMVTVHP A*0201 173 best31-39 aa25-43 PMTVLCSIDWFMVTVHPFM A*0201 196
(107) In the following, the T cell receptor sequences obtained are shown. The underlined sequences are the CDR sequences, wherein the first sequence in each T cell receptor chain is CDR1, followed by CDR2 and CDR3.
(108) 1. hCMV pp65-Specific T Cell Receptors
(109) TABLE-US-00006 TCR.sub.CD8-CMV#1: >V1.2J24_2C(V->A) SEQIDNO:4 MWGAFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQH AGEAPTFLSYNVLDGLEEKGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVADSWG KLQFGAGTQVVVTPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVY ITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVE KSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D2J2.1C2(C->T) SEQIDNO:5 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYCASSQ EGLAGASNNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGF YPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRN HFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATIL YEILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-CMV#4: >V3J43C SEQIDNO:6 MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVKCTYSVSGNPYLFWYV QYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCAVS ASNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.5D1J1.2C1(S->R) SEQIDNO:7 MRIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWY RQDPGMGLRLIHYSVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCAS SPQTGASFNYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATG FFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPR NHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATI LYEILLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD8-CMV#8: >V22J58C SEQIDNO:8 MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQ NPWGQLINLFYIPSGTKQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAVVRWETS GSRLTFGEGTQLTVNPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLV EKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V10.1DJ1.4C1 SEQIDNO:9 MGTRLFFYVAICLLWAGHRDAEITQSPRHKITETGRQVTLACHQTWNHNNMFWYRQ DLGHGLRLIHYSYGVQDTNKGEVSDGYSVSRSNTEDLPLTLESAASSQTSVYFCASSD PTEEKLFFGSGTQLSVLEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVE LSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD8-CMV#9: >V19J26C SEQIDNO:10 MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWY KQPPSGELVFLIRRNSFDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALSE GGSYGQNFVFGPGTRLSVLPYIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V13D2J2.1C2(MLSLPDSAWN->MG) SEQIDNO:11 MGTRLLCRVMLCLLGAGSVAAGVIQSPRHLIKEKRETATLKCYPIPRHDTVYWYQQ GPGQDPQFLISFYEKMQSDKGSIPDRFSAQQFSDYHSELNMSSLELGDSALYFCASSL RDEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVEL SWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQ FYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-CMV#10: >V24J49C SEQIDNO:12 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWY RWETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCARN TGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.5D1J1.2C1 SEQIDNO:13 MSIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWYR QDPGMGLRLIHYSVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCATQ LATGTNYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD8-CMV#11: >V16J36C SEQIDNO:14 MKPTLISVLVIIFILRGTRAQRVTQPEKLLSVFKGAPVELKCNYSYSGSPELFWYVQYS RQRLQLLLRHISRESIKGETADLNKGETSFHLKKPFAQEEDSAMYYCALGWANNLFF GTGTRLTVIPYIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFET DTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V25.1D1J2.2C2(T->G;M->G) SEQIDNO:15 MGTRLLCYGGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQ QDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASTE GTGHTGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-CMV#12: >V39J58C SEQIDNO:16 MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQD PGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDIETS GSRLTFGEGTQLTVNPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLV EKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V9D2J2.2C2(F->T) SEQIDNO:17 MGTRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQS LDQGLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSAL GGAGTGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-CMV#14: >V24J21C SEQIDNO:18 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWY RWETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCAFIN FNKFYFGSGTKLNVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D2J2.2C2(C->T) SEQIDNO:19 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQ VLGPGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-CMV#15: >V12.3J43C SEQIDNO:20 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFM WYRQYSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAM VNNNNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V12.4D1J1.4C1 SEQIDNO:21 MDSWTLCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHDYLFWYRQT MMRGLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSY GTYEKLFFGSGTQLSVLEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD8-CMV#16: >V13.1_2J50C SEQIDNO:22 MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQ ELGKRPQLIIDIRSNVGEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAATYDK VIFGPGTSLSVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITD KTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSF ETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V25.1J1.3C1(T1->GT) SEQIDNO:23 MGTRLLCYMGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQ QDPGMELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASSE TSFSGNTIYFGEGSWLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-CMV#1: >V21J43C SEQIDNO:24 METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFRQ DPGKGLTSLLLIQSSQREQTSGRLNASLDKSSGRSTLYIAASQPGDSATYLCAVKDND MRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYI TDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D1J1.1C1(C->T) SEQIDNO:25 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQ EKRGAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVE LSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-CMV#3: >V8.6_2J37_2C SEQIDNO:26 MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQ YPNQGLQLLLKYLSGSTLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSSY GSSNTGKLIFGQGTTLQVKPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.1D1J1.2C1(I->L) SEQIDNO:27 MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWY RQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCA SSTAGGRNYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGF FPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRN HFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATIL YEILLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-CMV#5: >V22J49C SEQIDNO:28 MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQ NPWGQLINLFYIPSGTKQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAAGSNTGN QFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYIT DKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKS FETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.2D2J2.3C2(G->A) SEQIDNO:29 MSLGLLCCAAFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWY RQDPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSQTSVYFCA SSSRGYGTDTQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGF YPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRN HFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATIL YEILLGKATLYAVLVSALVLMAMVICRKDSRG*;
2. NY-ESO-1-Specific T Cell Receptors
(110) TABLE-US-00007 TCR.sub.CD8-NY#2: >V3J28C SEQIDNO:30 MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVICCTYSVSGNPYLFWYV QYPNRGLQFLLKYITGDNLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCAVRP LYSGAGSYQLTFGKGTKLSVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQ SKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS CDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1_2J2.3C2 SEQIDNO:31 MLLLLLLLGPGSGLGAVVSQHPSRVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSL MLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSARNLPLT DTQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELS WWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQF YGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-NY#5: V24J3C SEQIDNO:32 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWY RWETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCAST SYSSASKIIFGSGTRLSIRPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.6D2J2.2C2(S->R) SEQIDNO:33 MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVTKRGQDVALRCDPISGHVSLYWYR QALGQGPEFLTYFNYEAQQDKSGLPNDRFSAERPEGSISTLTIQRTEQRDSAMYRCAS SHSSGGAGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-NY#6: >V17J47_2C SEQIDNO:34 METLLGVSLVILWLQLARVNSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYR QNSGRGLVHLILIRSNEREKHSGRLRVTLDTSKKSSSLLITASRAADTASYFCATDEYG NKLVFGAGTILRVKSYIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLV EKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V12.3D2J2.1C2(F->L) SEQIDNO:35 MDSWTLCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQT MMRGLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSY PGFNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-NY#8: >V8.6_2J9C(A->V) SEQIDNO:36 MLLLLVPVFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQ YPNQGLQLLLKYLSGSTLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSDQ GTGGFKTIFGAGTRLFVKANIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V28.1D1J1.1C1 SEQIDNO:37 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYR QDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASR GTVTSSLMNTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATG FFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPR NHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATI LYEILLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD8-NY#12: >V1.1J23C SEQIDNO:38 MWGAFLLYVSMKMGGTAGQSLEQPSEVTAVEGAIVQINCTYQTSGFYGLSWYQQH DGGAPTFLSYNALDGLEETGRFSSFLSRSDSYGYLLLQELQMKDSASYFCAVRDKQG GKLIFGQGTELSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVY ITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVE KSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V4.1D2J2.1C2(C->S) SEQIDNO:39 MGSRLLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNKKSLKCEQHMGHRAMYWY KQKAKKPPELMFVYSYEKLSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCAS MGKRGGNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-NY#13: >V5J33C SEQIDNO:40 MKTFAGFSFLFLWLQLDCMSRGEDVEQSLFLSVREGDSSVINCTYTDSSSTYLYWYK QEPGAGLQLLTYIFSNMDMKQDQRLTVLLNKKDKHLSLRIADTQTGDSAIYFCAERG QDSNYQLIWGAGTKLIIKPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.5_2D1J2.5C2(PG->TR;C->F) SEQIDNO:41 MGTRLLFWVLLCLLGAGPVDAGVTQSPTHLIKTRGQHVTLRCSPISGHKSVSWYQQV LGQGPQFIFQYYEKEERGRGNFPDRFSARQFPNYSSELNVNALLLGDSALYLCASSG WTGRSFGGGAQYFGPGTRLLVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGF YPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRN HFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATIL YEILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-NY#15: >V12.2_2J53C(K->I) SEQIDNO:42 MISLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWY RQYSGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVPYY WSSGGSNYKLTFGKGTLLTVNPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVS QSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V4.1D2J2.5C2(C->S) SEQIDNO:43 MGSRLLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNKKSLKCEQHMGHRAMYWY KQKAKKPPELMFVYSYEKLSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASS QSGLEETQYFGPGTRLLVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-NY#1: >V22J20C(DonorSNPN->K) SEQIDNO:44 MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQ NPWGQLINLFYIPSGTKQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAVNDYKLS FGAGTTVTVRANIQKPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITD KTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSF ETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V9D1J1.1Cl(F->T) SEQIDNO:45 MGTRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQS LDQGLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSPG VSGTTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-NY#3: >V12.3J54C SEQIDNO:46 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFM WYRQYSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAM SKGAQKLVFGQGTRLTINPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V11.2D2J2.2C2 SEQIDNO:47 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQI LGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSL GDSNTGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-NY#5: >V8.4_3J48C SEQIDNO:140 MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQ YPNQGLQLLLKYTTGATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVSR ANFGNEKLTFGTGTRLTIIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V4.1D1J1.5C1(GCKL.fwdarw.SNQV) SEQIDNO:141 MSNQVLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNKKSLKCEQHMGHRAMYWY KQKAKKPPELMFVYSYEKLSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASS QDPRGGPQHFGDGTRLSILEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-NY#7: >V8.6_2J13_2C SEQIDNO:142 MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQ YPNQGLQLLLKYLSGSTLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSKS GGYQKVTFGTGTKLQVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1D2J2.5C2 SEQIDNO:143 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQS LMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAAPGLA GGQGGSQYFGPGTRLLVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-NY#10: >V9.2_3J42C SEQIDNO:144 MNYSPGLVSLILLLLGRTRGDSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQY PGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCARAVN YGGSQGNLIFGKGTKLSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.9_3D2J2.7C2(S.fwdarw.R) SEQIDNO:145 MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYR QTLGQGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCAS SLGHEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-NY#11: >V8.1J23C SEQIDNO:146 MLLLLIPVLGMIFALRDARAQSVSQHNHHVILSEAASLELGCNYSYGGTVNLFWYVQ YPGQHLQLLLKYFSGDPLVKGIKGFEAEFIKSKFSFNLRKPSVQWSDTAEYFCAVNRR TGNQGGKLIFGQGTELSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V11.2D1J1.2C1 SEQIDNO:147 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQI LGQGPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSL GPYIDGAGCTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-NY#13: >V21_2J24_2C SEQIDNO:148 METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFRQ DPGKGLTSLLLIQSSQREQTSGRLNASLDKSSGRSTLYIAASQPGDSATYLCAVPTDS WGKLQFGAGTQVVVTPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.9_3D1J2.3C2(S.fwdarw.R) SEQIDNO:149 MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYR QTLGQGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCAS SSKLTGIPEGTDTQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLAT GFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNP RNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSAT ILYEILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-NY#16: >V8.4_3J10C SEQIDNO:150 MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQ YPNQGLQLLLKYTTGATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVKK GGGNKLTFGTGTQLKVELNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1D1J1.5C1 SEQIDNO:151 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQS LMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSATGPSE HQPQHFGDGTRLSILEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELS WWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQF YGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-NY#14: >V8.4_3J37_2C SEQIDNO:176 MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQ YPNQGLQLLLKYTTGATLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVSK GSSNTGKLIFGQGTTLQVKPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D2J1.3C1 SEQIDNO:177 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQ DPGGAGNTIYFGEGSWLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDF*;
3. TPTE-Specific T Cell Receptors:
(111) TABLE-US-00008 TCR.sub.CD8-TPT#3: >V27J16C SEQIDNO:48 MVLKFSVSILWIQLAWVSTQLLEQSPQFLSIQEGENLTVYCNSSSVFSSLQWYRQEPG EGPVLLVTVVTGGEVKKLKRLTFQFGDARKDSSLHITAAQPGDTGLYLCAGAQGQK LLFARGTMLKVDLNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYI TDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.9D2J2.2C2 SEQIDNO:49 MGTRLLCWMALCLLGADHADTGVSQNPRHKITKRGQNVTFRCDPISEHNRLYWYR QTLGQGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCAS SHLAGGNTGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGF YPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRN HFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATIL YEILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-TPT#35: >V19J17C SEQIDNO:50 MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWY KQPPSGELVFLIRRNSFDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALIE AAAGNKLTFGGGTRVLVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V12.4D2J2.7C2(L->F) SEQIDNO:51 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHDYLFWYRQT MMRGLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCAGSL RLAGAAEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#4: >V14/DV4J48C SEQIDNO:52 MSLSSLLKVVTASLWLGPGIAQKITQTQPGMFVQEKEAVTLDCTYDTSDPSYGLFWY KQPSSGEMIFLIYQGSYDQQNATEGRYSLNFQKARKSANLVISASQLGDSAMYFCAT ASNFGNEKLTFGTGTRLTIIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V29.1D1J1.2C1 SEQIDNO:53 MLSLLLLLLGLGSVFSAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSL TLIATANQGSEATYESGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCSVDRDREDGY TFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWV NGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLS ENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#5: >V38.2/DV8J40C SEQIDNO:54 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWY KQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAY SRTSGTYKYIFGTGTRLKVLANIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSC DVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V4.2D2J2.7C2(GCRL->SNQV) SEQIDNO:55 MSNQVLCCAVLCLLGAVPMETGVTQTPRHLVMGMTNKKSLKCEQHLGHNAMYWY KQSAKKPLELMFVYNFKEQTENNSVPSRFSPECPNSSHLFLHLHTLQPEDSALYLCAS SQEISGSSYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFY PDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNH FRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYE ILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#6: >V12.3J35C SEQIDNO:56 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFM WYRQYSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAM SAVSFGNVLHCGSGTQVIVLPHIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSC DVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; V5.4D1J1.3C1(PG->TR) SEQIDNO:57 MGTRLLCWVLLCLLGAGSVETGVTQSPTHLIKTRGQQVTLRCSSQSGHNTVSWYQQ ALGQGPQFIFQYYREEENGRGNFPPRFSGLQFPNYSSELNVNALELDDSALYLCASSF GENTIYFGEGSWLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVE LSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#8: >V38.1J45C SEQIDNO:58 MTRVSLLWAVVVSTCLESGMAQTVTQSQPEMSVQEAETVTLSCTYDTSENNYYLFW YKQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDTAMYFCA FMKHPSGGGADGLTFGKGTHLIIQPYIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D1J2.7C2(C->T) SEQIDNO:59 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSH ERGGAYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#11: >V17J27C SEQIDNO:60 METLLGVSLVILWLQLARVNSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYR QNSGRGLVHLILIRSNEREKHSGRLRVTLDTSKKSSSLLITASRAADTASYFCAGYNT NAGKSTFGDGTTLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.6_2D1J2.3C2(IS->LG) SEQIDNO:61 MSLGLLCCAAFPLLWAGPVNAGVTQTPKFRILKIGQSMTLQCAQDMNHNYMYWYR QDPGMGLKLIYYSVGAGITDKGEVPNGYNVSRSTTEDFPLRLELAAPSQTSVYFCASS FGQVWADTQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFY PDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNH FRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYE ILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#13: >V20_2J29C SEQIDNO:62 MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLFW YRQHPGKGPEFLFTLYSAGEEKEKERLKATLTKKESFLHITAPKPEDSATYLCAVQAS NSGNTPLVFGKGTRLSVIANIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V19D2J2.1C2 SEQIDNO:63 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYR QDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASS APHQRGTNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFY PDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNH FRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYE ILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#17: >V29/DV5J49C SEQIDNO:64 MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMF DYFLWYKKYPAEGPTFLISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYF CAASPNTGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVS QSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.2D1J2.7C2 SEQIDNO:65 MGTRLLFWVAFCLLGADHTGAGVSQSPSNKVTEKGKDVELRCDPISGHTALYWYRQ SLGQGLEFLIYFQGNSAPDKSGLPSDRFSAERTGGSVSTLTIQRTQQEDSAVYLCASSL TGGPYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#27: >V13.1_2J45C(DonorSNPN->K) SEQIDNO:66 MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQ ELGKRPQLIIDIRSNVGEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAALYSGG GADGLTFGKGTHLIIQPYIQKPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V19D1J1.1C1 SEQIDNO:67 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYR QDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSI GGGVNTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#33: >V29/DV5J42C(DonorSNPN->K) SEQIDNO:68 MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMF DYFLWYKKYPAEGPTFLISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYF CAARSYGGSQGNLIFGKGTKLSVICPNIQKPDPAVYQLRDSKSSDKSVCLFTDFDSQTN VSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V24.1D2J2.1C2 SEQIDNO:69 MASLLFFCGAFHLLGTGSMDADVTQTPRNRITKTGKRIMLECSQTKGHDRMYWYRQ DPGLGLRLIYYSFDVKDINKGEISDGYSVSRQAQAKFSLSLESAIPNQTALYFCATSDT GTSRNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#38: >V39J18C(DonorSNPN->K) SEQIDNO:70 MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQD PGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVGFRG STLGRLYFGRGTQLTVWPDIQKPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.5_2D1J1.4C1(PG->TR) SEQIDNO:71 MGTRLLCWVLLCLLGAGPVDAGVTQSPTHLIKTRGQHVTLRCSPISGHKSVSWYQQ VLGQGPQFIFQYYEKEERGRGNFPDRFSARQFPNYSSELNVNALLLGDSALYLCASS WGQGNEKLFFGSGTQLSVLEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPD HVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFR CQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEIL LGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#42: >V25J10C SEQIDNO:72 MLLITSMLVLWMQLSQVNGQQVMQIPQYQHVQEGEDFTTYCNSSTTLSNIQWYKQR PGGHPVFLIQLVKSGEVKKQKRLTFQFGEAKKNSSLHITATQTTDVGTYFCAGSTGG GNKLTFGTGTQLKVELNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.8D2J2.7C2(GTR->DIW;L->V) SEQIDNO:73 MDIWLVCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQ QALGQGPEFLTYFQNEAQLDKSGLPSDRFFAERPEGSVSTLKIQRTQQEDSAVYLCAS SDFYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#45: >V13.2J23C SEQIDNO:74 MAGIRALFMYLWLQLDWVSRGESVGLHLPTLSVQEGDNSIINCAYSNSASDYFIWYK QESGKGPQFIIDIRSNMDKRQGQRVTVLLNKTVICHLSLQIAATQPGDSAVYFCAETRQ GGKLIFGQGTELSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDV YITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLV EKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1D1J1.2C1(ISLLLPGSLAGmissingfollowingGPG) SEQIDNO:75 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQS LMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAPPGVT VRAYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#48: >V38.2/DV8J42C SEQIDNO:76 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWY KQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAY RNYGGSQGNLIFGKGTKLSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVS QSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V28D1J1.1C1 SEQIDNO:77 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYR QDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASN RLNTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#49: >V38.1J49C SEQIDNO:78 MTRVSLLWAVVVSTCLESGMAQTVTQSQPEMSVQEAETVTLSCTYDTSENNYYLFW YKQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDTAMYFCA FMKNTGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQS KDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSC DVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V19D2J2.2C2 SEQIDNO:79 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYR QDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASR RLDGLGIGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#51: >V13.1_2J53C SEQIDNO:80 MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQ ELGKRPQLIIDIRSNVGEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAALSGGS NYKLTFGKGTLLTVNPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V14D1J1.1C1 SEQIDNO:81 MVSRLLSLVSLCLLGAKHIEAGVTQFPSHSVIEKGQTVTLRCDPISGHDNLYWYRRV MGKEIKFLLHFVKESKQDESGMPNNRFLAERTGGTYSTLKVQPAELEDSGVYFCASS QQENTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#52: >V8.3J54C(AdditionalMA) SEQIDNO:82 MAMLLELIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYV QSPGQGLQLLLKYFSGDTLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVG AQGAQKLVFGQGTRLTINPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.1D2J2.7C2(I->L) SEQIDNO:83 MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWY RQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCA SSEAGGSSFEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFY PDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNH FRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYE ILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#54: >V9.2J23C SEQIDNO:84 MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQY PGEGLQLLLKATKADDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALGRG KLIFGQGTELSVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYI TDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1D1J1.1C1(ISLLLPGSLAGmissingfollowingGPG) SEQIDNO:85 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQS LMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAVDSDL EAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSW WVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFY GLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#55: >V38.2/DV8J34C SEQIDNO:86 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWY KQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAY RSAVYNTDKLIFGTGTRLQVFPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQ SKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS CDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.1J2.1C2 SEQIDNO:87 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQT PGQGLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSFS SYNEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVE LSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#57: >V8.1J27C SEQIDNO:88 MLLLLIPVLGMIFALRDARAQSVSQHNHHVILSEAASLELGCNYSYGGTVNLFWYVQ YPGQHLQLLLKYFSGDPLVKGIKGFEAEFIKSKFSFNLRKPSVQWSDTAEYFCAVNAR DNAGKSTFGDGTTLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.1D2J2.7C2 SEQIDNO:89 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQT PGQGLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASRGE PSSYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#59: >V39J49C SEQIDNO:90 MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQD PGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDNEF YFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITD KTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSF ETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V7.9_3D2J2.4C2(S->R) SEQIDNO:91 MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYR QTLGQGPEFLTYFQNEAQLEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCAS SLLGAGNIQYFGAGTRLSVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#67: >V12.3J9C SEQIDNO:92 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFM WYRQYSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAL YTGGFKTIFGAGTRLFVKANIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKD SDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDV KLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.1D2J2.7C2 SEQIDNO:93 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQT PGQGLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSFM GTEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVEL SWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQ FYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#76: >V8.3J57C SEQIDNO:94 MLLELIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSP GQGLQLLLKYFSGDTLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGAFT RGGSEKLVFGKGMKLTVNPYIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V19D2_2J2.7C2 SEQIDNO:95 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYR QDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCATG SYVGYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#77: >V14/DV4_3J50C SEQIDNO:96 MSLSSLLKVVTASLWLGPGIAQKITQTQPGMFVQEKEAVTLDCTYDTSDPSYGLFWY KQPSSGEMIFLIYQGSYDQQNATEGRYSLNFQKARKSANLVISASQLGDSAMYFCAM REGLAKTSYDKVIFGPGTSLSVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVS QSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V20.1D2J2.2C2(ISLLLPGSLAGismissingfollowingGPG) SEQIDNO:97 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQS LMLMATSNEGSKATYEQGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAPGTGH SAGELFFGEGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVE LSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQV QFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#78: >V8.6_2J21C SEQIDNO:98 MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQ YPNQGLQLLLKYLSGSTLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVGPN NFNKFYFGSGTKLNVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDS DVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVK LVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V2D1J1.6_2C1(L->I) SEQIDNO:99 MDIWLVCWAIFSLLKAGLTEPEVTQTPSHQVTQMGQEVILRCVPISNHLYFYWYRQI LGQKVEFLVSFYNNEISEKSEIFDDQFSVERPDGSNFTLKIRSTKLEDSAMYFCASSPV GGYNSPLHFGNGTRLTVTEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#79: >V38.2/DV8J39C SEQIDNO:100 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWY KQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAY RSYNAGNMLTFGGGTRLMVKPHIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVS QSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.1D2J2.1C2 SEQIDNO:101 MGSRLLCLVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQT PGQGLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSDT SGGGGEQFFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#82: >V38.2/DV8J39C SEQIDNO:102 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWY KQPPSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAY RSAGLLLTFGGGTRLMVKPHIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V 19D1J2.7C2 SEQIDNO:103 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYR QDPGQGLRLIYYSQIVNDFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASS KAPGQGNTQGWEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLA TGFYPDHVELSWWVNGKEVHSGVSTDPQPLICEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSA TILYEILLGKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#87: >V39J31C SEQIDNO:104 MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQD PGKSLESLFVLLSNGAVKQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDMW NNNARLMFGDGTQLVVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V5.1J2.6C2 SEQIDNO:105 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQT PGQGLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSLA QSGANVLTFGAGSRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD4-TPT#91: >V20_2J53C SEQIDNO:106 MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLFW YRQDPGKGPEFLFTLYSAGEEKEKERLKATLTKKESFLHITAPKPEDSATYLCAVLGG SNYKLTFGKGTLLTVNPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSD VYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKL VEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.1DlJ2.7C2(I->L) SEQIDNO:107 MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWY RQDPGMGLRLIYYSASEGTTDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCAI SRDSYEQYFGPGTRLTVTEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDSRG*; TCR.sub.CD8-TPT#35/2: V19J17C SEQIDNO:188 MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWY KQPPSGELVFLIRRNSFDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALIE AAAGNKLTFGGGTRVLVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSK DSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCD VKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V6.2oderVB6.3D1J1.2C1(A.fwdarw. V) SEQIDNO:189 MSLGLLCCGVFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWY RQDPGMGLRLIHYSVGEGTTAKGEVPDGYNVSRLKKQNFLLGLESAAPSQTSVYFCA SSDGYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDH VELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRC QVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILL GKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#9: >V23/DV6J49C SEQIDNO:190 MDKILGASFLVLWLQLCWVSGQQKEKSDQQQVKQSPQSLIVQKGGISIINCAYENTA FDYFPWYQQFPGKGPALLIAIRPDVSEKKEGRFTISFNKSAKQFSLHIMDSQPGDSATY FCAASFYTGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNV SQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPE SSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >V3.1D1J1.2C1(C.fwdarw. T) SEQIDNO:191 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYK QDSKKFLKIMFSYNNKELIINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQ EALGGGYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFP DHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHF RCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEI LLGKATLYAVLVSALVLMAMVKRKDF*; TCR.sub.CD4-TPT#48/2: >V8.3J43C(E.fwdarw. V) SEQIDNO:192 MLLVLIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSP GQGLQLLLKYFSGDTLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGAYD MRFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYI TDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEK SFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS*; >28D1J1.1C1 SEQIDNO:193 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYR QDPGLGLRLIYFSYDVKMKEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASN RLNTEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHV ELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQ VQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDF*;
4. PLAC1-Specific T Cell Receptors
(112) TABLE-US-00009 TCR.sub.CD8-mPL#2: >V6D.6_5J33C(DFSoderDSS.fwdarw.NSF) SEQIDNO:152 MNSFPGFVAVILLILGRTHGDSVTQTEGQVTVSESKSLIINCTYSATSIGYPNLFWYVR YPGEGLQLLLKVITAGQKGSSRGFEATYNKEATSFHLQKASVQESDSAVYYCALSDS NYQLIWGSGTKLIIKPDIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFI TDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFE TDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V2D1J1.3C1 SEQIDNO:153 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQS AKKPLEFMFSYSYQKLMDNQTASSRFQPQSSKKNHLDLQITALKPDDSATYFCASSP DNSGNTLYFGEGSRLIVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDH VELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQF HGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATL YAVLVSTLVVMAMVKRKNS*; TCR.sub.CD8-mPL#8: >V9D.1_1orV9D.1_2J12C(L.fwdarw.F) SEQIDNO:154 MLLVFISFLGIHFFLDVQTQTVSQSDAHVTVFEGDSVELRCNYSYGGSIYLSWYIQHH GRGLQFLLKYYSGNPVVQGVNGFKAEFSKSDSSFHLRKASVHWSDSAVYFCAVSAG GYKVVFGSGTRLLVSPDIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGT FITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSF ETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V5D2J2.1C2 SEQIDNO:155 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQS AEKPPELMFLYNLKQLIRNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSPGG AEQFFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELS WWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGL SEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAV LVSGLVLMAMVKKKNS*; TCR.sub.CD8-mPL#9: >V4D.4_2J44C(Q.fwdarw.E) SEQIDNO:156 MERNLGAVLGILWVQICWVRGDQVEQSPSALSLHEGTGSALRCNFTTTMRAVQWFQ QNSRGSLINLFYLASGTKENGRLKSTFNSKESYSTLHIRDAQLEDSGTYFCAAPFVTGS GGKLTLGAGTRLQVNLDIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGT FITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSF ETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V2D2J2.7C2 SEQIDNO:157 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQS AKKPLEFMFSYSYQKLMDNQTASSRFQPQSSKKNHLDLQITALKPDDSATYFCASSQ DGWGYEQYFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPD HVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQV QFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKA TLYAVLVSGLVLMAMVKKKNS*; TCR.sub.CD8-mPL#11: >V6D.6_2J9_2C(DF.fwdarw.NS) SEQIDNO:158 MNSSPGFVAVILLILGRTHGDSVTQTEGPVTVSESESLIINCTYSATSIAYPNLFWYVR YPGEGLQLLLKVITAGQKGSSRGFEATYNKETTSFHLQKASVQESDSAVYYCALGLG YKLTFGTGTSLLVDPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFI TDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFE TDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; V2D1J1.3C1 SEQIDNO:159 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQS AKKPLEFMFSYSYQKLMDNQTASSRFQPQSSKKNHLDLQITALKPDDSATYFCASSG DNSGNTLYFGEGSRLIVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDH VELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQF HGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATL YAVLVSTLVVMAMVKRKNS*; TCR.sub.CD8-mPL#12: >V4D.4_2J27C(Q.fwdarw.E) SEQIDNO:160 MERNLGAVLGILWVQICWVRGDQVEQSPSALSLHEGTGSALRCNFTTTMRAVQWFQ QNSRGSLINLFYLASGTKENGRLKSTFNSKESYSTLHIRDAQLEDSGTYFCAAVNTNT GKLTFGDGTVLTVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFI TDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFE TDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V30D1J2.2C2 SEQIDNO:161 MWTFLLLLWSQGSVFSVLLYQKPNRDICQSGTSLKIQCVADSQVVSMFWYQQFQEQ SLMLMATANEGSEATYESGFTKDKFPISRPNLTFSTLTVNNARPGDSSIYFCSSRTPNT GQLYFGEGSKLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELS WWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGL SEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAV LVSGLVLMAMVKKKNS*; TCR.sub.CD8-mPL#14: >V9D.1_2J12C SEQIDNO:162 MLLVLISFLGIHFFLDVQTQTVSQSDAHVTVFEGDSVELRCNYSYGGSIYLSWYIQHH GHGLQFLLKYYSGNPVVQGVNGFEAEFSKSDSSFHLRKASVHWSDSAVYFCAVSSG GYKVVFGSGTRLLVSPDIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGT FITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSF ETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V5D1J1.1C1 SEQIDNO:163 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQS AEKPPELMFLYNLKQLIRNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSQGG TEVFFGKGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELS WWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGL SEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAV LVSTLVVMAMVKRKNS*; TCR.sub.CD8-mPL#17: >V14.1J31_1oder_2C SEQIDNO:164 MDKILTATFLLLGLHLAGVNGQQQEKRDQQQVRQSPQSLTVWEGETAILNCSYEDST FNYFPWYQQFPGEGPALLISIRSVSDKKEDGRFTIFFNKREKKLSLHITDSQPGDSATY FCAPNNRIFFGDGTQLVVKPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTM ESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLT EKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V13.2D2J2.1C2 SEQIDNO:165 MGSRLFFVLSSLLCSKHMEAAVTQSPRNKVAVTGGKVTLSCNQTNNHNNMYWYRQ DTGHGLRLIHYSYGAGSTEKGDIPDGYKASRPSQENFSLILELATPSQTSVYFCASLGY NYAEQFFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVE LSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFH GLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLY AVLVSGLVLMAMVKKKNS*; TCR.sub.CD8-mPL#19: >V6D.3J22C SEQIDNO:166 MNNSPALVTVMLFILGRTHGDSVIQMQGQVTLSENDFLFINCTYSTTGYPTLFWYVQ YSGEGPQLLLQVTTANNKGSSRGFEATYDKGTTSFHLQKTSVQEIDSAVYYCAMSDA SGSWQLIFGSGTQLTVMPDIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMES GTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTE KSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V13.3D1J1.6C1 SEQIDNO:167 MGSRLFFVVLILLCAKHMEAAVTQSPRSKVAVTGGKVTLSCHQTNNHDYMYWYRQ DTGHGLRLIHYSYVADSTEKGDIPDGYKASRPSQENFSLILELASLSQTAVYFCASSPD RPSYNSPLYFAAGTRLTVTEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPD HVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQV QFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKA TLYAVLVSTLVVMAMVKRKNS*; TCR.sub.CD8-mPL#20: >V12.3_3J38C SEQIDNO:168 MRPGTCSVLVLLLMLRRSNGDGDSVTQKEGLVTLTEGLPVMLNCTYQTIYSNAFLF WYVHYLNESPRLLLKSSTDNKRTEHQGFHATLHKSSSSFHLQKSSAQLSDSALYYCA LNNVGDNSKLIWGLGTSLVVNPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPK TMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDA TLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V5D2J1.1C1 SEQIDNO:169 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQS AEKPPELMFLYNLKQLIRNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSQYG GANTEVFFGKGTRLTVVEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDH VELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQF HGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATL YAVLVSTLVVMAMVKRKNS*; TCR.sub.CD8-mPL#22: >V 13D.2J34_2C(V.fwdarw.L) SEQIDNO:170 MKRLLCSLLGLLCTQVCWVKGQQVQQSPASLVLQEGENAELQCNFSSTATRLQWFY QHPGGRLVSLFYNPSGTKHTGRLTSTTVTNERRSSLHISSSQTTDSGTYFCAAASNTN KVVFGTGTRLQVLPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFIT DKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFET DMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V20D1J2.1C2 SEQIDNO:171 MLLLLLLLGPGCGLGALVYQYPRRTICKSGTSMRMECQAVGFQATSVAWYRQSPQK TFELIALSTVNSAIKYEQNFTQEKFPISHPNLSFSSMTVLNAYLEDRGLYLCGVDRANY AEQFFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELS WWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGL SEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAV LVSGLVLMAMVKKKNS*; TCR.sub.CD8-mPL#25: >V8.1_3J21C SEQIDNO:194 MHSLLGLLLWLQLTRVNSQLAEENSWALSVHEGESVTVNCSYKTSITALQWYRQKS GKGPAQLILIRSNEREKRNGRLRATLDTSSQSSSLSITATRCEDTAVYFCATDNVLYFG SGTKLTVEPNIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVL DMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLN FQNLSVMGLRILLLKVAGFNLLMTLRLWSS*; >V31D2J2.1C2 SEQIDNO:195 MLYSLLAFLLGMFLGVSAQTIHQWPVAEIKAVGSPLSLGCTIKGKSSPNLYWYWQAT GGTLQQLFYSITVGQVESVVQLNLSASRPKDDQFILSTEKLLLSHSGFYLCAWKLGNY AEQFFGPGTRLTVLEDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELS WWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGL SEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAV LVSGLVLMAMVKKKNS*;