Antigen-Specific T Cell Receptors and T Cell Epitopes

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. A method for providing antigen-specific lymphoid cells comprising the steps: (a) providing a single antigen-reactive T cell from a sample comprising T cells, wherein said sample is obtained from a subject previously exposed to said antigen; (b) providing a nucleic acid encoding a T cell receptor having the specificity of the T cell receptor of said single antigen-reactive T cell; and (c) introducing said nucleic acid into a lymphoid cell to provide said antigen-specific lymphoid cells.

2. A method for providing an antigen-specific T cell receptor having a defined MHC restriction comprising the steps: (a) providing a single antigen-reactive T cell from a sample comprising T cells, wherein said sample is obtained from a subject previously exposed to said antigen; (b) providing a nucleic acid encoding a T cell receptor having the specificity of the T cell receptor of said single antigen-reactive T cell; (c) introducing said nucleic acid into a lymphoid cell to provide antigen-specific lymphoid cells; and (d) determining the MHC restriction of said antigen-specific lymphoid cells.

3. A method for identifying a T cell epitope in an antigen comprising the steps: (a) providing a single antigen-reactive T cell from a sample comprising T cells, wherein said sample is obtained from a subject previously exposed to said antigen; (b) providing a nucleic acid encoding a T cell receptor having the specificity of the T cell receptor of said single antigen-reactive T cell; (c) introducing said nucleic acid into a lymphoid cell to provide antigen-specific lymphoid cells; and (d) determining the epitope specificity of said antigen-specific lymphoid cells.

4. The method of any one of claims 1 to 3, wherein said nucleic acid is RNA.

5. The method of any one of claims 1 to 4, wherein said step of providing a nucleic acid encoding a T cell receptor having the specificity of the T cell receptor of said single antigen-reactive T cell comprises providing a nucleic acid encoding a T cell receptor comprising at least the CDR sequences, preferably at least the variable region of the T cell receptor of said single antigen-reactive T cell.

6. The method of any one of claims 1 to 5, wherein said subject is seropositive for said antigen or an agent comprising said antigen.

7. The method of any one of claims 1 to 6, wherein said single antigen-reactive T cell is isolated from the sample comprising T cells using flow cytometry.

8. A peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 108 to 139, 172, 173, 175, 178 to 187 and 196 or a variant of said amino acid sequence.

9. A nucleic acid encoding the peptide of claim 8 or a cell comprising said nucleic acid.

10. A cell that presents the peptide of claim 8 or a procession product thereof.

11. An immunoreactive cell or a T cell receptor reactive with a peptide of claim 8, or a polypeptide chain of said T cell receptor.

12. A T cell receptor -chain or a T cell receptor comprising said T cell receptor -chain, wherein said T cell receptor -chain is selected from the group consisting of: (i) a T cell receptor -chain comprising at least one, preferably two, more preferably all three of the CDR sequences of a T cell receptor -chain selected from SEQ ID NOs: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194 or a variant thereof and (ii) a T cell receptor -chain comprising a T cell receptor -chain sequence selected from SEQ ID NOs: 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194 or a variant thereof.

13. A T cell receptor -chain or a T cell receptor comprising said T cell receptor -chain, wherein said T cell receptor -chain is selected from the group consisting of: (i) a T cell receptor -chain comprising at least one, preferably two, more preferably all three of the CDR sequences of a T cell receptor -chain selected from SEQ ID NOs: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 177, 189, 191, 193, and 195 or a variant thereof and (ii) a T cell receptor -chain comprising a T cell receptor -chain sequence selected from SEQ ID NOs: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 177, 189, 191, 193, and 195 or a variant thereof.

14. A T cell receptor selected from the group consisting of: (I) a T cell receptor comprising: (i) a T cell receptor -chain comprising at least one, preferably two, more preferably all three of the CDR sequences of the T cell receptor -chain of SEQ ID NO: x or a variant thereof, and (ii) a T cell receptor -chain comprising at least one, preferably two, more preferably all three of the CDR sequences of a T cell receptor -chain of SEQ ID NO: x+1 or a variant thereof; wherein x selected from 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194 and (II) a T cell receptor comprising: (i) a T cell receptor -chain comprising the T cell receptor -chain sequence of SEQ ID NO: x or a variant thereof, and (ii) a T cell receptor -chain comprising the T cell receptor -chain sequence of SEQ ID NO: x+1 or a variant thereof; wherein x selected from 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 176, 188, 190, 192, and 194.

15. A nucleic acid encoding the T cell receptor chain or T cell receptor according to any one of claims 11 to 14 or a cell comprising the T cell receptor chain or T cell receptor according to any one of claims 11 to 14 or said nucleic acid.

16. A pharmaceutical composition comprising one or more of: (i) the peptide of claim 8; (ii) the nucleic acid of claim 9 or 15; (iii) the cell of any one of claims 9, 10 and 15; (iv) the immunoreactive cell of claim 11; and (v) the T cell receptor of any one of claims 11 to 14.

17. A method for inducing an immune response in a subject, comprising administering to the subject a pharmaceutical composition of claim 16.

18. A method for stimulating, priming and/or expanding T cells, comprising contacting T cells with one or more of: (i) the peptide of claim 8; (ii) the nucleic acid of claim 9; and (iii) the cell of claim 9 or 10.

19. A method for determining an immune response in a subject, comprising determining T cells reactive with a peptide of claim 8 or the cell of claim 10 in a biological sample isolated from the subject.

20. A method for determining cytotoxic activity comprising the steps of: (i) providing a sample comprising target cells producing a reporter enzyme; (ii) subjecting the target cells to an agent the cytotoxic activity of which is to be determined; and ii) subjecting the sample to a detection assay to establish the level of reporter enzyme contained in viable cells in the sample.

Description

FIGURES

[0361] FIG. 1: Representation of the TCR-CD3 complex. The intracytoplasmic CD3 immunoreceptor tyrosine-based activation motifs (ITAMs) are indicated as cylinders (adapted from The T cell receptor facts book, M P Lefranc, G Lefranc, 2001).

[0362] FIG. 2. Technology platform for TCR isolation/validation. The approach integrates all steps from isolation of antigen-specific T cells (top) to TCR cloning (middle) and TCR validation (bottom). Patients are screened for autoantibody responses against the antigen of interest by CrELISA (Crude lysate Enzyme-Linked ImmunoSorbent Assay). Antigen-specific T cells from seropositive donors are stimulated with peptide or RNA loaded autologous DCs and IFN secreting CD8+ or CD4+ T cells are isolated by flow cytometry (top). Single cells are harvested in multiwell-plates and subjected to first-strand cDNA synthesis and enrichment by a global PCR amplification step. TCR / variable regions are cloned into vectors for in vitro transcription (IVT) containing the constant region cassettes (middle). TCR / chain RNAs are transferred into CD4+ or CD8+ T cells, cocultured with APCs expressing the appropriate antigen and HLA molecules and tested for functional reprogramming of engineered T cells (bottom).

[0363] FIG. 3. Flow cytometric sorting of pp65-specific CD8.sup.+ T cells from a CMV-seropositive donor after one week of expansion. IFNg secreting CD.sup.8+ T cells were isolated after rechallenge with autologous pp65 RNA-transfected iDCs. Control: iDCs transfected with eGFP RNA.

[0364] FIG. 4. Verification of TCR surface expression on TCR-transfected SupT1 cells analyzed by flow cytometry. SupT1 cells electroporated with TCR / chain RNAs were stained with a pan TCR antibody and analyzed by flow cytometry. SupT1 cells electroporated without RNA served as a negative control.

[0365] FIG. 5. Specificity testing of TCRs obtained from CMV-pp65-specific CD8+ T cells of a CMV seropositive donor after in vitro expansion by IFN-ELISPOT. TCR-engineered IVSB cells were tested on antigen-loaded autologous iDCs and K562-A*0201 cells for specific recognition of pp65 peptide pool, pp65.sub.495-503 or pp65 IVT RNA. Partially overlapping peptides derived from TPTE were used as control peptide pool and SSX-2.sub.241-249 was used as single peptide control. The tyrosinase derived Tyr.sub.368-376 epitope was applied as a positive control. Control TCR: TCR cloned from a CMV seronegative donor.

[0366] FIG. 6. Determination of HLA restriction and peptide specificity of TCR.sub.CD8-CMV#1 by IFN-ELISPOT. TCR-transgenic IVSB cells were analyzed for recognition of K562 cells expressing selected HLA class I alleles of the donor pulsed with pp65 overlapping peptides or without antigen as a control. K562-B*3501 cells were subsequently used to analyze TCR.sub.CD8-CMV#1-mediated recognition of individual 15-mer peptides derived from CMV-pp65.

[0367] FIG. 7. Specificity testing of TCRs cloned from ex vivo isolated CMV-pp65-specific CD8+ T cells of a CMV seropositive donor by IFN-ELISPOT. IVSB cells were transfected with TCR / chain RNAs and stimulated with K562-A*0201 pulsed with pp65.sub.495-503. The unrelated peptide SSX-2.sub.241-249 and a TCR cloned from a CMV-seronegative donor served as negative, the tyrosinase derived Tyr.sub.368-376 epitope served as positive control.

[0368] FIG. 8. Specific killing of target cells by TCR-transfected T cells analyzed by luciferase cytotoxicity assay. Peptide-pulsed K562 target cells expressing the appropriate HLA allelotype were used as targets for IVSB cells engineered with CMV-pp65-specific TCRs. As a reference, killing of Tyr.sub.368-376-pulsed target cells mediated by the endogenous receptor was analyzed. A TCR obtained from a CMV seronegative donor was used as control to exclude unspecific lysis. E:T: effector-to-target ratio.

[0369] FIG. 9. Specificity testing of TCRs isolated from NY-ESO-1-specific CD8.sup.+ T cells by IFN-ELISPOT. TCR.sub.CD8-NY#2 and -#5 were transferred into IVSB cells and tested for recognition of autologous iDCs loaded with NY-ESO-1 RNA or peptide pool. Negative controls: iDCs pulsed with TPTE peptide pool; a control TCR isolated from a healthy donor. Positive control: Tyr.sub.368-376-pulsed K562-A*0201.

[0370] FIG. 10. Identification of HLA restricting elements for NY-ESO-1-specific TCRs by IFN-ELISPOT. TCR-engineered IVSB cells were analyzed by IFNg-ELISPOT for recognition of K562 cells transfected with individual HLA class I alleles of the donor and pulsed with NY-ESO-1 peptide pool. Negative controls: HIV-gag peptide pool; K562 electroporated without HLA RNA (mock). Positive control: Tyr.sub.368-376 peptide.

[0371] FIG. 11: Identification of 15mer peptides recognized by NY-ESO-1-specific TCRs by IFN-ELISPOT. TCR-transfected IVSB T cells were analyzed for recognition of K562 cells expressing the appropriate HLA class I allele and pulsed with individual partially overlapping 15-mers derived from NY-ESO-1.

[0372] FIG. 12. Epitope mapping for NY-ESO-1-specific TCRs by IFN-ELISPOT. IVSB cells transfected with TCR.sub.CD8-NY#5, #6, #8 or #15 were analyzed for recognition of K562-B*3508 cells pulsed with individual nonamer peptides covering amino acids 77-107 of the NY-ESO-1 protein.

[0373] FIG. 13. Specific killing of target cells mediated by TCR.sub.CD8-NY#2 analyzed by luciferase cytotoxicity assay. Specific lysis of K562-A*6801 cells pulsed with NY-ESO-1 peptide pool by TCR.sub.CD8-NY#2-transfected IVSB cells was analyzed using different effector-to-target ratios (E:T). Control: target cells pulsed with TPTE peptide pool.

[0374] FIG. 14: Determination of HLA restriction elements for NY-ESO-1-specific TCRs obtained from CD4+ T cells by IFN-ELISPOT. TCR-transfected CD4+ T cells were analyzed for recognition of K562 expressing individual HLA class II alleles of the patient pulsed with peptide pools of either NY-ESO-1 or HIV-gag as a negative control.

[0375] FIG. 15. Epitope mapping for TCR.sub.CD4-NY#5 by IFN-ELISPOT. TCR-engineered CD4+ T cells were tested for recognition of K562 cells expressing the appropriate HLA class II allele and pulsed with partially overlapping 15-mers representing the NY-ESO-1 protein.

[0376] FIG. 16. Determination of HLA restriction and peptide specificity of TCR.sub.CD8-TPT#3 by IFN-ELISPOT. TCR-transfected IVSB cells were analyzed for recognition of K562 cells expressing HLA class I molecules of the patient pulsed with TPTE peptide pool (top). K562-B*3501 cells pulsed with individual 15mer representing the whole antigen (middle) and 9-mer peptides covering amino acids 521-535 of TPTE (bottom) were used to define the epitope recognized by TCR.sub.CD8-TPT#3. Anchor amino acids of the recognized epitope for binding to HLA B*3501 are shown in bold.

[0377] FIG. 17. Determination of HLA restriction elements for TPTE-specific TCRs isolated from CD4+ T cells by IFN-ELISPOT. TCR-transfected CD4+ T cells were analyzed for recognition of K562 cells transfected with HLA class II alleles of the patient and pulsed with overlapping peptides corresponding to TPTE or HIV-gag as a control.

[0378] FIG. 18. Epitope mapping for TPTE-specific TCRs isolated from CD4+ T cells by IFN-ELISPOT. Epitope locations of TCRs were determined using TCR-transfected CD4+ T cells in combination with K562 cells transfected with the appropriate HLA class II antigen and pulsed with individual partially overlapping 15-mer peptides covering the TPTE protein.

[0379] FIG. 19. Flow cytometric sorting of PLAC1-specific CD8+ T cells obtained from immunized mice. Spleen cells of PLAC1-immunized HLA A*0201-transgenic mice (A2.1/DR1 mice) were pulsed with overlapping peptides corresponding to PLAC1 or a control antigen (WT1). 24 h later cells were harvested, stained with fluorochrome-conjugated antibodies and CD3+/CD8+/CD137+ cells were isolated. Histogram plots were gated on CD3+/CD8+ cells. M1-5: PLAC1-immunized mice; Con1-3: control mice.

[0380] FIG. 20. Specificity testing of TCRs cloned from CD8+ T cells of PLAC1-immunized mice by IFN-ELISPOT. TCR-engineered IVSB cells were tested for recognition of K562-A*0201 cells pulsed with overlapping peptides corresponding to PLAC1 or NY-ESO-1 as a control antigen. As a positive control, IFN secretion in response to Tyr.sub.368-376-pulsed target cells was analyzed.

[0381] FIG. 21. Determination of peptide specificity of TCR.sub.CD8-Pl#8 by IFN-ELISPOT. TCR-transfected CD8+ T cells were tested for specific recognition of K562-A*0201 cells pulsed with individual partially overlapping 15-mer peptides covering the PLAC1 protein.

[0382] FIG. 22. Definition of A*0201-restricted immunodominant epitopes recognized by PLAC1-specific TCRs by IFN-ELISPOT. TCR-transfected IVSB cells were analyzed for recognition of K562-A*0201 cells pulsed with individual 9-mer peptides covering amino acids 25-43 of PLAC1 to define the epitope recognized by TCR.sub.CD8-Pl#11. Recognized peptides are shown in bold. Positive control: PLAC1 15-mer peptide 7.

EXAMPLES

[0383] 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

[0384] Serotyping

[0385] 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.

[0386] Cell Lines and Reagents

[0387] 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-Mel and AK-EBV cells.

[0388] Peripheral Blood Mononuclear Cells (PBMCs), Monocytes and Dendritic Cells (DCs)

[0389] 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.

[0390] Peptides and Peptide Pulsing of Stimulator Cells

[0391] 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.

[0392] Vectors for In Vitro Transcription (IVT) of RNA

[0393] 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)).

[0394] 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)).

[0395] 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 pST-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.

[0396] Primers were purchased from Operon Biotechnologies, Cologne, Germany.

[0397] Generation of In Vitro Transcribed (IVT) RNA and Transfer into Cells

[0398] 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).

[0399] In Vitro Expansion of Antigen-Specific T Cells

[0400] 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.

[0401] Single-Cell Sorting of Antigen-Specific CD8+ or CD4+ T Cells after IFN Secretion Assay

[0402] 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.

[0403] In Vivo Priming of T Cells by Intranodal Immunization of HLA A2.1/DR1 Mice with IVT RNA

[0404] 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.

[0405] Harvest of Spleen Cells

[0406] 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.

[0407] Single-Cell Sorting of Antigen-Specific CD8+ T Cells after CD137 Staining

[0408] For antigen-specific restimulation 2.5106/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.

[0409] RNA Extraction, SMART-Based cDNA Synthesis and Unspecific Amplification from Sorted Cells

[0410] 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.

[0411] 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 g RNA extracted from patient-derived PBMCs.

[0412] Design of PCR Primers for TCR and HLA Amplification

[0413] For design of human TCR consensus primers, all 67 TCR-VB 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 3end were designed to anneal to as many leader sequences as possible and equipped with a 15 bp 5extension 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.

[0414] 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.

[0415] 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.

[0416] PCR Amplification and Cloning of V(D)J and HLA Sequences

[0417] 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 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.

[0418] 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 AsiSI-digested IVT vector. EciI- or SapI-sites within the inserts were mutated using QuikChange Site-Directed Mutagenesis Kits (Stratagene, La Jolla, Calif.).

[0419] Flow Cytometric Analyses

[0420] 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).

[0421] Luciferase Cytotoxicity Assay

[0422] 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.

[0423] 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.

[0424] 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.

[0425] 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.

[0426] ELISPOT (Enzyme-Linked ImmunoSPOT Assay)

[0427] 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). 2-510.sup.4/well antigen presenting stimulator cells were plated in triplicates together with 0.3-310.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-Pp65

[0428] The TCR isolation/validation protocol (FIG. 2) was' established using the human cytomegalovirus (CMV)-phosphoprotein 65 (CMV-pp65, pp65, 65 kDa lower matrix phosphoprotein, UL83) as a model antigen, that is known to induce high frequencies of antigen-specific T cells in the peripheral blood of healthy donors. CMV is a ubiquitous -herpesvirus infecting the host via body fluids such as blood or saliva.

[0429] In healthy individuals primary CMV infection and reactivation of endogenous latent viruses is controlled by the immune system, while in immunocompromised individuals such as transplant recipients or AIDS patients it results in significant morbidity and mortality.

[0430] 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).

[0431] 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 (FIG. 2 top, FIG. 3).

[0432] 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 (FIG. 2 middle).

[0433] 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 (FIG. 4).

[0434] For functional validation of cloned TCRs, the monospecific T cell line IVSB recognizing the tyrosinase-derived epitope Tyr.sub.368-376 (Wlfel 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 (FIG. 2 bottom, FIG. 5). As the TCRs were generated by stimulation with whole antigen, they were evaluated for mediating specific recognition of autologous DCs either pulsed with pp65 peptide pool or pp65 encoding IVT RNA. An unrelated TPTE peptide pool was used as a control. TCR.sub.CD8-CMV#1 and TCR.sub.CD8-CMV#4 both specifically recognized pp65 expressing target cells compared to a control TCR isolated from a CMV seronegative donor.

[0435] 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 (FIG. 6 top). HLA B*3501 was identified as restriction element. Analysis of individual 15-mers of the pp65 peptide pool revealed recognition of peptides P30, P31 and P32, with reactivity decreasing gradually (FIG. 6 bottom). This localized the epitope recognized by TCR.sub.CD8-CMV#1 within the region of amino acids 117-131 of pp65 suggesting its identity with the previously reported and highly immunogenic HLA-B*3501-restricted epitope CMV-pp65.sub.123-131 (Seq. IPSINVHHY) (Gavin, M. A. et al. (1993), J. Immunol. 151, 3971-3980).

[0436] 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.

[0437] 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.495-503 and activated IFN secreting T cells were sorted by flow cytometry.

[0438] Specificity of TCRs obtained ex vivo from the CD8+ T cells after presensitation with pp65.sub.495-503 was analyzed in an IFN-ELISPOT assay. As shown in FIG. 7, four of six TCRs were able to redirect IVSB cells to recognize K562-A*0201 cells pulsed with pp65.sub.495-503 compared to a control peptide. In contrast, IVSB cells equipped with a control TCR isolated from a CMV-seronegative donor did not secrete IFN upon coculture with K562-A*0201 cells pulsed with pp65.sub.495-503.

[0439] 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.

[0440] 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 (FIG. 8).

[0441] 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.

[0442] 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

[0443] 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.

[0444] 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).

[0445] 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 FIG. 9, TCRs recognized DCs either pulsed with NY-ESO-1 peptide pool or transfected with NY-ESO-1 RNA, the latter confirming recognition of a naturally processed epitope.

[0446] 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 FIG. 10.

[0447] 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 (FIG. 11).

[0448] Remarkably, epitopes of all seven TCRs were localized to amino acids 85-111 of the NY-ESO-1 protein (FIG. 11, 12). This region is known to undergo efficient proteosomal cleavage due to hydrophobic sequences and is processed into multiple epitopes with various HLA restrictions (Valmori, D. et al. (2007), Clin. Immunol. 122, 163-172). By screening serial nonamers, we narrowed down the HLA-B*3508 restricted epitope of TCR.sub.CD8-NY#5, #6, #8 and #15 to NY-ESO-1.sub.92-100 (seq. LAMPFATPM) (FIG. 12).

[0449] 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 FIG. 13, IVSB effectors were reprogrammed by TCR.sub.CD8-NY#2 to specifically lyse target cells at different E:T ratios.

[0450] 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 (FIG. 14) and confinement of epitope localizations (FIG. 15) revealed that 7 of these TCRs recognized epitopes in a peptide stretch comprising aa 117-147 in the context of different HLA class II allelotypes, suggesting a hot spot for T helper cell epitopes (Table 5).

[0451] 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

[0452] 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.

[0453] 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.

[0454] 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 FIG. 16. This TCR was shown to reprogram IVSB cells for specific recognition of K562 cells presenting TPTE peptides on HLA B*3501 (FIG. 16 top). The HLA-B*3501-restricted epitope could be localized to TPTE 15-mers P130, P131 and P132, with highest reactivity to peptide P131 representing amino acids 521-535 of TPTE (FIG. 16 middle). By analyzing serial nonamers covering this region, the novel epitope TPTE.sub.527-535 (seq. YPSDFAVEI) could be defined, which complies with the requirements of a B*3501 binding motif with proline as an anchor residue at position 2, aspartic acid as a charged residue at position 4 and isoleucine as a hydrophobic amino acid at position 9 (Falk, K. et al. (1993), Immunogenetics 38, 161-162) (FIG. 16 bottom).

[0455] 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 (FIG. 17). After determination of HLA restrictions TPTE-specific TCRs were analyzed for recognition of TPTE 15mer peptides in order to localize the recognized epitopes (FIG. 18).

[0456] 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

[0457] 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.

[0458] 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 (FIG. 19). Notably, in all five mice a significant percentage of PLAC1-specific T cells (ranging from 16-48% of CD8+ cells) could be established by intranodal immunization with PLAC1 IVT RNA.

[0459] 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 (FIG. 20). A total of 11 TCRs were shown to mediate specific recognition of K562-A*0201 cells pulsed with peptides derived from PLAC1 compared to a control antigen. Remarkably, IFN secretion mediated by the PLAC1-specific TCRs was even higher compared to those mediated by the endogenous TCR of IVSB effectors. Epitope mapping by the use single-peptide-pulsed HLA allele-expressing K562 target cells, disclosed that all identified PLAC1-specific TCRs recognize 15mer peptides 7 and 8 representing amino acid 25-43 of PLAC1 (FIG. 21). By screening serial nonamers covering this region, we identified two HLA-A*0201 restricted epitopes: PLAC1 amino acids 28-36 and amino acids 30-41, with best recognition of amino acids 31-39 (FIG. 22, Table 5). Notably, all PLAC1-specific TCRs obtained from 4 different mice were shown to recognize these two epitopes indicating preferential procession of these PLAC1 peptides as well as efficient binding and presentation on HLA A*0201. All TCRs mediated increased IFN secretion in response to amino acids 31-39 compared to amino acids 28-36. The latter was properly recognized by some of the TCRs only.

[0460] 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

[0461] 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.

[0462] 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).

[0463] 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.

[0464] 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.

[0465] Tables

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

TABLE-US-00002 TABLE 2 NY-ESO-1-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-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

TABLE-US-00003 TABLE 3 TPTE-specific TCRs Recognized Designation TCR alpha chain.sup.a TCR beta chain.sup.a HLA class I/II 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

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-mP1#2 V6D.6_5 J33 C V2 D1 J1.3 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#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-mP1#9 V4D.4_2 J44 C V2 D2 J2.7 C2 A*0201 aa 25-43 TCR.sub.CD8-mP1#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-mP1#12 V4D.4_2 J27 C V30 D1 J2.2 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#14 V9D.1_2 J12 C V5 D1 J1.1 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#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-mP1#19 V6D.3 J22 C V13.3 D1 J1.6 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#20 V12.3_3 J38 C V5 D2 J1.1 C1 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#22 V13D.2 J34_2 C V20 D1 J2.1 C2 A*0201 aa 28-36, 30-41, best 31-39 TCR.sub.CD8-mP1#25 V8.1_3 J21 C V31 D2 J2.1 C2 A*0201 aa 25-43

TABLE-US-00005 TABLE 5 T cell epitopes derived from the antigens hCMV pp65, NY-ESO-I, TPTE, PLAC1 HLA class I/II SEQ ID Antigen Epitope Amino acid sequence restriction NO: hCMV pp65 aa 117-139, PLKMLNIPSINVHHYPSAAERKH B*3501 108 best 117-131 aa 495-503 NLVPMVATV A*0201 109 aa 117-139 PLKMLNIPSINVHHYPSAAERKH DRB1*0701 108 aa 337-359 VELRQYDPVAALFFFDIDLLLQR DRB1*0701 110 NY-ESO-I aa 92-100 LAMPFATPM B*3508 111 aa 93-107 AMPFATPMEAELARR A*6801 112 aa 97-111 ATPMEAELARRSLAQ B*0702 113 aa 85-99 SRLLEFYLAMPFATP DRB5*0202 114 aa 117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*0401 115 aa 117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*1101 115 aa 117-139 PVPGVLLKEFTVSGNILTIRLTA DRB1*1601 115 aa 117-139 PVPGVLLKEFTVSGNILTIRLTA DRB3*0201 115 aa 129-147 SGNILTIRLTAADHRQLQL DRB5*0202 116 aa 165-180 CFLPVFLAQPPSGQRR DRB1*0401 117 aa 121-135 VLLKEFTVSGNILTI DRB3*0201 175 TPTE aa 185-199 RNIPRWTHLLRLLRL B*0702 118 aa 527-535 YPSDFAVEI B*3501 119 aa 53-71 SPISESVLARLSKFEVEDA DRB1*1401 120 aa 81-95 IKKIVHSIVSSFAFG DRB1*1501 121 aa 109-127 ILADLIFTDSKLYIPLEYR DRB1*0701 122 aa 117-135 DSKLYIPLEYRSISLAIAL DRB1*1501 123 aa 141-155 VLLRVFVERRQQYFS DRB1*1301 124 aa 173-187 DVVYIFFDIKLLRNI DRB1*1501 125 aa 177-191 IFFDIKLLRNIPRWT DRB1*1501 126 aa 177-195 IFFDIKLLRNIPRWTHLLR DRB1*1301 127 aa 177-195 IFFDIKLLRNIPRWTHLLR DRB5*0202 127 aa 181-195 IKLLRNIPRWTHLLR DRB3*0201/2 128 aa 181-195 IKLLRNIPRWTHLLR DRB3*0301 128 aa 217-231 KLIRRRVSENKRRYT DRB1*1301 129 aa 217-231 KLIRRRVSENKRRYT DRB5*0202 129 aa 221-235 RRVSENKRRYTRDGF DRB1*1301 130 aa 269-283 RFLDKKHRNHYRVYN DRB1*1301 131 aa 277-291 NHYRVYNLCSERAYD DRB1*1601 132 aa 393-411 YVAYFAQVKHLYNWNLPPR DRB1*1501 133 aa 405-423 NWNLPPRRILFIKHFIIYS DRB4*0101 134 aa 409-423 PPRRILFIKHFIIYS DRB1*1301 135 aa 413-427 ILFIKHFIIYSIPRY DRB1*1501 136 aa 417-435 KHFIIYSIPRYVRDLKIQI DRB1*1301 137 aa 417-435 KHFIIYSIPRYVRDLKIQI DRB1*1401 137 aa 453-467 VLDNITTDKILIDVF DQA1*0102/B1*0602 138 aa 453-467 VLDNITTDKILIDVF DQA1*0103/B1*0602 138 aa 453-467 VLDNITTDKILIDVF DQA1*0103/B1*0603 138 aa 497-515 WLHTSFIENNRLYLPKNEL DRB1*1401 139 aa 102-110 VLLDVTLIL A*0201 178 aa 164-172 AIIVILLLV A*0201 179 aa 188-196 PRWTHLLRL B*0702 180 aa 53-67 SPISESVLARLSKFE DQA1*0102/DQB1*0602 181 aa 77-91 YDSKIKKIVHSIVSS DQA1*0102/DQB1*0602 182 aa 121-135 YIPLEYRSISLAIAL DRB1*0701 183 aa 145-159 VFVERRQQYFSDLFN DRB1*0701 184 aa 149-163 RRQQYFSDLFNILDT DRB1*1501 185 aa 157-171 LFNILDTAIIVILLL DRB1*1501 186 aa 245-259 RIIAMSFPSSGRQSF DQA1*0102/DQB1*0602 187 PLAC1 aa 28-36 VLCSIDWFM A*0201 172 aa 30-41, CSIDWFMVTVHP A*0201 173 best 31-39 aa 25-43 PMTVLCSIDWFMVTVHPFM A*0201 196

[0466] 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. .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.b designations 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.c The TCR beta gene is V12.4_1 or V12.4_2.sup.d The TCR beta gene is V6.2 or V6.3.sup.e The TCR alpha gene is V9D.1_1 or V9D.1_2.sup.f The TCR alpha gene is J31_1J or J31_2.sup.g Promiscous TCRs recognizing more than one epitope.sup.aa=amino acids

TABLE-US-00006 1.hCMVpp65-specificTcellreceptors TCR.sub.CD8-CMV#1: SEQIDNO:4;> V1.2J24_2C(V> A) MWGAFLLYVSMKMGGTTGQNIDQPTEMTATEGAIVQINCTYQTSGFNGLFWYQQHAGEAPTFLSYNVLDGLEE KGRFSSFLSRSKGYSYLLLKELQMKDSASYLCAVADSWGKLQFGAGTQVVVTPDIQNPDPAVYQLRDSKSSDK SVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:5;> V3.1D2J2.1C2(C> T) MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQEGLAGASNNEQFFGPGTRLTVLEDLKNVFPPE VAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVS ATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-CMV#4: SEQIDNO:6;> V3J43C MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVKCTYSVSGNPYLFWYVQYPNRGLQFLLKYITGD NLVKGSYGFEAEFNKSQTSFHLKKPSALVSDSALYFCAVSASNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSK SSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFP SPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:7;> V6.5D1J1.2C1(S> R) MRIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWYRQDPGMGLRLIHYSVGAGI TDQGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCASSPQTGASFNYGYTFGSGTRLTVVEDLNKVFPPEV AVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSA TFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDF* TCR.sub.CD8-CMV#8: SEQIDNO:8;> V22J58C MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQNPWGQLINLFYIPSGT KQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAVVRWETSGSRLTFGEGTQLTVNPDIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDVTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:9;> V10.1DJ1.4C1 MGTRLFFYVAICLLWAGHRDAEITQSPRHKITETGRQVTLACHQTWNHNNMFWYRQDLGHGLRLIHYSYGVQD TNKGEVSDGYSVSRSNTEDLPLTLESAASSQTSVYFCASSDPTEEKLFFGSGTQLSVLEDLNKVFPPEVAVFE PSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDF* TCR.sub.CD8-CMV#9: SEQIDNO:10;> V19J26C MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWYKQPPSGELVFLIRRNS FDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALSEGGSYGQNFVFGPGTRLSVLPYIQNPDPAVY QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIP EDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:11;> V13D2J2.1C2(MLSLPDSAWN> MG) MGTRLLCRVMLCLLGAGSVAAGVIQSPRHLIKEKRETATLKCYPIPRHDTVYWYQQGPGQDPQFLISFYEMKQ SDKGSIPDRFSAQQFSDYHSELNMSSLELGDSALYFCASSLRDEQFFGPGTRLTVLEDLKNVFPPEVAVFEPS EAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNP RNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLV SALVLMAMVKRKDSRG* TCR.sub.CD8-CMV#10: SEQIDNO:12;> V24J49C MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRWETAKSPEALFVMT LNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCARNTGNQFYFGTGTSLTVIPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:13;> V6.5D1J1.2C1 MSIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWYRQDPGMGLRLIHYSVGAGI TDQGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCATQLATGTNYGYTFGSGTRLTVVEDLNKVFPPEVAV FEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDF* TCR.sub.CD8-CMV#11: SEQIDNO:14;> V16J36C MKPTLISVLVIIFILRGTRAQRVTQPEKLLSVFKGAPVELKCNYSYSGSPELFWYVQYSRQRLQLLLRHISRE SIKGFTADLNKGETSFHLKKPFAQEEDSAMYYCALGWANNLFFGTGTRLTVIPYIQNPDPAVYQLRDSKSSDK SVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:15;> V25.1D1J2.2C2(T> G;M> G) MGTRLLCYGGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNS TEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASTEGTGHTFELFFGEGSRLTVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-CMV#12: SEQIDNO:16;> V39J58C MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQDPGKSLESLFVLLSNGAV KQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDIETSGSRLTFGEGTQLTVNPDIQNPDPAVYQLRDSK SSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFP SPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:17;> V9D2J2.2C2(F> T) MGTRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQFLIQYYNGEE RAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSALGGAGTGELFFGEGSRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-CMV#14: SEQIDNO:18;> V24J21C MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRWETAKSPEALFVMT LNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCAFINFNKFYFGSGTKLNVKPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:19;> V3.1D2J2.2C2(C> T) MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQVLGPGELFFGEGSRLTVLEDLKNVFPPEVAVF EPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDSRG* TCR.sub.CD8-CMV#15: SEQIDNO:20;> V12.3J43C MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQYSRKGPELLMYTY SSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAMVNNNNDMRFGAGTRLTVKPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDIF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:21;> V12.4D1J1.4C1 MDSWTLCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHDYLFWYRQTMMRGLELLIYFNNNVP IDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSYGTYEKLFFGSGTQLSVLEDLNKVFPPEVAVF EPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYA VLVSLAVLMAMVKRKDF* TCR.sub.CD8-CMV#16: SEQIDNO:22;> V13.1_2J50C MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQELGKRPQLLIDIRSNV GEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAATYDKVIFGPGTSLSVIPNIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:23;> V25.1J1.3C1(TI> GT) MGTRLLCYMGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGMELHLIHYSYGVNS TEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCASSETSFSGNTIYFGEGSWLTVVEDLNKVFPPEVAV FEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDF* TCR.sub.CD4-CMV#1: SEQIDNO:24;> V21J43C METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFRQDPGKGLTSLLLIQSSQ REQTSGRLNASLDKSSGRSTLYIAASQPGDSATYLCAVKDNDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKSS DKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSP ESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:25;> V3.1D1J1.1C1(C> T) MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQEKRGAFFGQGTRLTVVEDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDF* TCR.sub.CD4-CMV#3: SEQIDNO:26;> V8.6_2J37_2C MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGS TLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSSYGSSNTGKLIFGQGTTLQVKPDIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:27;> V6.1D1J1.2C1(I> L) MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGT TDKGEVPNGYNVSRLNICREFSLRLESAAPSQTSVYFCASSTAGGRNYGYTFGSGTRLTVVEDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDF* TCR.sub.CD4-CMV#5: SEQIDNO:28;> V22J49C MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQNPWGQLINLFYIPSGT KQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAAGSNTGNQFYFGTGTSLTVIPNIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPS PESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:29;> V6.2D2J2.3C2(G> A) MSLGLLCCAAFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWYRQDPGMGLRLIHYSVGEGT TAKGEVPDGYNVSRLKICQNFLLGLESAAPSQTSVYFCASSSRGYGTDTQYFGPGTRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWVVVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSA TFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVICRKDSRG* 2.NY-ESO-I-specificTcellreceptors TCR.sub.CD8-NY#2: SEQIDNO:30;> V3J28C MASAPISMLAMLFTLSGLRAQSVAQPEDQVNVAEGNPLTVKCTYSVSGNPYLFWYVQYPNRGLQFLLKYITGD NLVKGSYGFEAEFNKSQTSFHLICKPSALVSDSALYFCAVRPLYSGAGSYQLTFGKGTKLSVIPNIQNPDPAV YQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:31;> V20.1_2J2.3C2 MLLLLLLLGPGSGLGAVVSQHPSRVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSARNLPLTDTQYFGPGTRLTVLEDLKNVFPPEVAVFEP SEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDSRG* TC12.sub.CD8-NY#5: SEQIDNO:32;> V24J3C MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRWETAKSPEALFVMT LNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCASTSYSSASKIIFGSGTRLSIRPNIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:33;> V7.6D2J2.2C2(S> R) MGTRLLCWVVLGFLGTDHTGAGVSQSPRYKVTKRGQDVALRCDPISGHVSLYWYRQALGQGPEFLTYFNYEAQ QDKSGLPNDRFSAERPEGSISTLTIQRTEQRDSAMYRCASSHSSGGAGELFFGEGSRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-NY#6: SEQIDNO:34;> V17J47_2C METLLGVSLVILWLQLARVNSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYRQNSGRGLVHLILIRSNE REKHSGRLRVTLDTSKKSSSLLITASRAADTASYFCATDEYGNKLVFGAGTILRVKSYIQNPDPAVYQLRDSK SSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFP SPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:35;> V12.3D2J2.1C2(F> L) MDSWILCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMRGLELLIYFNNNVP IDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSYPGFNEQFFGPGTRLTVLEDLKNVFPPEVAVF EPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDSRG* TCR.sub.CD8-NY#8: SEQIDNO:36;> V8.6_2J9C(A> V) MLLLLVPVFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGS TLVKGINGFEAEFNKSQTSFHLRICPSVHISDTAEYFCAVSDQGTGGFKTIFGAGTRLFVKANIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:37;> V28.1D1J1.1C1 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGLGLRLIYFSYDVKM KEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASRGTVTSSLMNTEAFFGQGTRLTVVEDLNKVFPPE VAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVS ATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDF* TCR.sub.CD8-NY#12: SEQIDNO:38;> V1.1J23C MWGAFLLYVSMKMGGTAGQSLEQPSEVTAVEGAIVQINCTYQTSGFYGLSWYQQHDGGAPTFLSYNALDGLEE TGRFSSFLSRSDSYGYLLLQELQMKDSASYFCAVRDKQGGKLIFGQGTELSVKPNIQNPDPAVYQLRDSKSSD KSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPE SSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:39;> V4.1D2J2.1C2(C> S) MGSRLLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNICKSLKCEQHMGHRAMYWYKQKAKKPPELMFVYSYEK LSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASMGKRGGNEQFFGPGTRLTVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATI LYEILLGKATLYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-NY#13: SEQIDNO:40;> V5J33C MKTFAGFSFLFLWLQLDCMSRGEDVEQSLFLSVREGDSSVINCTYTDSSSTYLYWYKQEPGAGLQLLTYIFSN MDMKQDQRLTVLLNKKDKHLSLRIADTQTGDSAIYFCAERGQDSNYQLIWGAGTKLIIKPDIQNPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDT FFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:41;> V5.5_2D1J2.5C2(PG> TR;C> F) MGTRLLFWVLLCLLGAGPVDAGVTQSPTHLIKTRGQHVTLRCSPISGHKSVSWYQQVLGQGPQFIFQYYEKEE RGRGNFPDRFSARQFPNYSSELNVNALLLGDSALYLCASSGWTGRSFGGGAQYFGPGTRLLVLEDLKNVFPPE VAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVS ATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKA TLYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-NY#15: SEQIDNO:42;> V12.22J53C(K> I) MISLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIASLNCTYSDRGSQSFFWYRQYSGKSPELIMSIYS NGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVPYYWSSGGSNYKLTFGKGILLTVNPNIQNPDPAV YQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSII PEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:43;> V4.1D2J2.5C2(C> S) MGSRLLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNICKSLKCEQHMGHRAMYWYKQKAKKPPELMFVYSYEK LSINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASSQSGLEETQYFGPGTRLLVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-NY#1: SEQIDNO:44;> V22J20C(DonorSNPN> K) MKRILGALLGLLSAQVCCVRGIQVEQSPPDLILQEGANSTLRCNFSDSVNNLQWFHQNPWGQLINLFYIPSGT KQNGRLSATTVATERYSLLYISSSQTTDSGVYFCAVNDYKLSFGAGTTVTVRANIQKPDPAVYQLRDSKSSDK SVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPES SCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:45;> V9D1J1.1C1(F> T) MGTRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQGLQFLIQYYNGEE RAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSPGVSGTTEAFFGQGTRLTVVEDLNKVFPPEVAV FEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDF* TCR.sub.CD4-NY#3: SEQIDNO:46;> V12.3J54C MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQYSRKGPELLMYTY SSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAMSKGAQKLVFGQGTRLTINPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:47;> V11.2D2J2.2C2 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGV VDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSLGDSNTGELFFGEGSRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-NY#5: SEQIDNO:140;> V8.4_3J48C MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQYPNQGLQLLLKYTTGA TLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVSRANFGNEKLTFGTGTRLTIIPNIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:141;> V4.1D1J1.5C1(GCKL.fwdarw. SNQV) MSNQVLCCAVLCLLGAVPIDTEVTQTPKHLVMGMTNKKSLKCEQHMGHRAMYWYKQKAKKPPELMFVYSYEKL SINESVPSRFSPECPNSSLLNLHLHALQPEDSALYLCASSQDPRGGPQHFGDGTRLSILEDLNKVFPPEVAVF EPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDF* TCR.sub.CD4-NY#7: SEQIDNO:142;> V8.6_2J13_2C MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGS TLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVSKSGGYQKVTFGTGTKLQVIPNIQNPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSHPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:143;> V20.1D2J2.5C2 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAAPGLAGGQGGSQYFGPGTRLLVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-NY#10: SEQIDNO:144;> V9.2_3J42C MNYSPGLVSLILLLLGRTRGDSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLKATKAD DKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCARAVNYGGSQGNLIFGKGTKLSVKPNIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:145;> V7.9_3D2J2.7C2(S.fwdarw. R) MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQ LEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSLGHEQYFGPGTRLTVTEDLKNVFPPEVAVFEP SEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDSRG* TCR.sub.CD4-NY11: SEQIDNO:146;> V8.1J23C MLLLLIPVLGMIFALRDARAQSVSQHNHHVILSEAASLELGCNYSYGGTVNLFWYVQYPGQHLQLLLKYFSGD PLVKGIKGFEAEFIKSKFSFNLRKPSVQWSDTAEYFCAVNRRTGNQGGKLIFGQGTELSVKPNIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:147;> V11.2D1J1.2C1 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQGPKLLIQFQNNGV VDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSLGPYIDGAGCTFGSGTRLTVVEDLNKVFPPEV AVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSA TFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDF* TCR.sub.CD4-NY#13: SEQIDNO:148;> V21_2J24_2C METLLGLLILWLQLQWVSSKQEVTQIPAALSVPEGENLVLNCSFTDSAIYNLQWFRQDPGKGLTSLLLIQSSQ REQTSGRLNASLDKSSGRSTLYIAASQPGDSATYLCAVPTDSWGKLQFGAGTQVVVTPDIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:149;> V7.9_3D1J2.3C2(S.fwdarw. R) MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQ LEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSSKLTGIPEGTDTQYFGPGTRLTVLEDLKNVFP PEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLR VSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLG KATLYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-NY#16: SEQIDNO:150;> V8.4_3J10C MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQYPNQGLQLLLKYTTGA TLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVKKGGGNKLTFGTGTQLKVELNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:151;> V20.1D1J1.5C1 MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSATGPSEHQPQHFGDGTRLSILEDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDF* TCR.sub.CD4-NY#14: SEQIDNO:176;> V8.4_3J37_2C MLLLLVPVLEVIFTLGGTRAQSVTQLGSHVSVSEGALVLLRCNYSSSVPPYLFWYVQYPNQGLQLLLKYTTGA TLVKGINGFEAEFKKSETSFHLTKPSAHMSDAAEYFCAVSKGSSNTGKLIFGQGTTLQVKPDIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:177;> V3.1D2J1.3C1 MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQDPGGAGNTIYFGEGSWLTVVEDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDF* 3.TPTE-specificTcellreceptors: TCR.sub.CD8-TPT#3: SEQIDNO:48;> V27J16C MVLKFSVSILWIQLAWVSTQLLEQSPQFLSIQEGENLTVYCNSSSVFSSLQWYRQEPGEGPVLLVTVVTGGEV KKLKRLTFQFGDARKDSSLHITAAQPGDTGLYLCAGAQGQKLLFARGTMLKVDLNIQNPDPAVYQLRDSKSSD KSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPE SSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:49;> V7.9D2J2.2C2 MGTRLLCWMALCLLGADHADTGVSQNPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQ LEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSHLAGGNTGELFFGEGSRLTVLEDLKNVFPPEV AVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSA TFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD8-TPT#35: SEQIDNO:50;> V19J17C MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWYKQPPSGELVFLIRRNS FDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALIEAAAGNKLTFGGGTRVLVKPNIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:51;> V12.4D2J2.7C2(L> F) MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHDYLFWYRQTMMRGLELLIYFNNNVP IDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCAGSLRLAGAAEQYFGPGTRLTVTEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#4: SEQIDNO:52;> V14/DV4J48C MSLSSLLKVVTASLWLGPGIAQKITQTQPGMFVQEKEAVTLDCTYDTSDPSYGLFWYKQPSSGEMIFLIYQGS YDQQNATEGRYSLNFQKARKSANLVISASQLGDSAMYFCATASNFGNEKLTFGTGTRLTIIPNIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:53;> V29.1D1J1.2C1 MLSLLLLLLGLGSVFSAVISQKPSRDICQRGTSLTIQCQVDSQVTMMFWYRQQPGQSLTLIATANQGSEATYE SGFVIDKFPISRPNLTFSTLTVSNMSPEDSSIYLCSVDRDREDGYTFGSGTRLTVVEDLNKVFPPEVAVFEPS EAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNP RNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLV SALVLMAMVKRKDF* TCR.sub.CD4-TPT#5: SEQIDNO:54;> V38.2/DV8J40C MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYSRTSGTYKYIFGTGTRLKVLANIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:55;> V4.2D2J2.7C2(GCRL> SNQV) MSNQVLCCAVLCLLGAVPMETGVTQTPRHLVMGMTNKKSLKCEQHLGHNAMYWYKQSAKKPLELMFVYNFKEQ TENNSVPSRFSPECPNSSHLFLHLHTLQPEDSALYLCASSQEISGSSYEQYFGPGTRLTVTEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#6: SEQIDNO:56;> V12.3J35C MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQYSRKGPELLMYTY SSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAMSAVSFGNVLHCGSGTQVIVLPHIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:57;> V5.4D1J1.3C1(PG> TR) MGTRLLCWVLLCLLGAGSVETGVTQSPTHLIKTRGQQVTLRCSSQSGHNTVSWYQQALGQGPQFIFQYYREEE NGRGNFPPRFSGLQFPNYSSELNVNALELDDSALYLCASSFGENTIYFGEGSWLTVVEDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDF* TCR.sub.CD4-TPT#8: SEQIDNO:58;> V38.1J45C MTRVSLLWAVVVSTCLESGMAQTVTQSQPEMSVQEAETVTLSCTYDTSENNYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDTAMYFCAFMKHPSGGGADGLTFGKGTHLIIQPYIQNPDPA VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:59;> V3.1D1J2.7C2(C> T) MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMFSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSHERGGAYEQYFGPGTRLTVTEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#11: SEQIDNO:60;> V17J27C METLLGVSLVILWLQLARVNSQQGEEDPQALSIQEGENATMNCSYKTSINNLQWYRQNSGRGLVHLILIRSNE REKHSGRLRVTLDTSKKSSSLLITASRAADTASYFCAGYNTNAGKSTFGDGTTLTVKPNIQNPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:61;> V6.62D1J2.3C2(IS> LG) MSLGLLCCAAFPLLWAGPVNAGVTQTPKFRILKIGQSMTLQCAQDMNHNYMYWYRQDPGMGLKLIYYSVGAGI TDKGEVPNGYNVSRSTTEDFPLRLELAAPSQTSVYFCASSFGQVWADTQYFGPGTRLTVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#13: SEQIDNO:62;> V20_2J29C MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLFWYRQHPGKGPEFLFTLYS AGEEKEKERLKATLTKKESFLHITAPKPEDSATYLCAVQASNSGNTPLVFGKGTRLSVIANIQNPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDT FFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:63;> V19D2J2.1C2 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVND FQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSAPHQRGTNEQFFGPGTRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#17: SEQIDNO:64;> V29/DV5J49C MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMFDYFLWYKKYPAEGPTFL ISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYFCAASPNTGNQFYFGTGTSLTVIPNIQNPDPA VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:65;> V7.2D1J2.7C2 MGTRLLFWVAFCLLGADHTGAGVSQSPSNKVTEKGKDVELRCDPISGHTALYWYRQSLGQGLEFLIYFQGNSA PDKSGLPSDRFSAERTGGSVSTLTIQRTQQEDSAVYLCASSLTGGPYEQYFGPGTRLTVTEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#27: SEQIDNO:66;> V13.1_2J45C(DonorSNPN> K) MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQELGKRPQLIIDIRSNV GEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAALYSGGGADGLTFGKGTHLIIQPYIQKPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDT FFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:67;> V19D1J1.1C1 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVND FQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSIGGGVNTEAFFGQGTRLTVVEDLNKVFPPEVAV FEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#33: SEQIDNO:68;> V29/DV5J42C(DonorSNPN> K) MAMLLGASVLILWLQPDWVNSQQKNDDQQVKQNSPSLSVQEGRISILNCDYTNSMFDYFLWYKKYPAEGPTFL ISISSIKDKNEDGRFTVFLNKSAKHLSLHIVPSQPGDSAVYFCAARSYGGSQGNLIFGKGTKLSVKPNIQKPD PAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNN SIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:69;> V24.1D2J2.1C2 MASLLFFCGAFHLLGTGSMDADVTQTPRNRITKTGKRIMLECSQTKGHDRMYWYRQDPGLGLRLIYYSFDVKD INKGEISDGYSVSRQAQAKFSLSLESAIPNQTALYFCATSDTGTSRNEQFFGPGTRLTVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#38: SEQIDNO:70;> V39J18C(DonorSNPN> K) MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQDPGKSLESLFVLLSNGAV KQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVGFRGSTLGRLYFGRGTQLTVWPDIQKPDPAVYQLRDS KSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFF PSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:71;> V5.5_2D1J1.4C1(PG> TR) MGTRLLCWVLLCLLGAGPVDAGVTQSPTHLIKTRGQHVTLRCSPISGHKSVSWYQQVLGQGPQFIFQYYEKEE RGRGNFPDRFSARQFPNYSSELNVNALLLGDSALYLCASSWGQGNEKLFFGSGTQLSVLEDLNKVFPPEVAVF EPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#42: SEQIDNO:72;> V25J10C MLLITSMLVLWMQLSQVNGQQVMQIPQYQHVQEGEDFTTYCNSSTTLSNIQWYKQRPGGHPVFLIQLVKSGEV KKQKRLTFQFGEAKKNSSLHITATQTTDVGTYFCAGSTGGGNKLTFGTGTQLKVELNIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQINVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPS PESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:73;> V7.8D2J2.7C2(GTR> DIW;L> V) MDIWLVCWVVLGFLGTDHTGAGVSQSPRYKVAKRGQDVALRCDPISGHVSLFWYQQALGQGPEFLTYFQNEAQ LDKSGLPSDRFFAERPEGSVSTLKIQRTQQEDSAVYLCASSDFYEQYFGPGTRLTVTEDLKNVFPPEVAVFEP SEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#45: SEQIDNO:74;> V13.2J23C MAGIRALFMYLWLQLDWVSRGESVGLHLPTLSVQEGDNSIINCAYSNSASDYFIWYKQESGKGPQFIIDIRSN MDKRQGQRVTVLLNKTVICHLSLQIAATQPGDSAVYFCAETRQGGKLIFGQGTELSVKPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:75;> V20.1D1J1.2C1(ISLLLPGSLAGmissingfollowingGPG) MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAPPGVTVRAYGYTFGSGTRLTVVEDLNKVFPPEVAVF EPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#48: SEQIDNO:76;> V38.2/DV8J42C MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRNYGGSQGNLIFGKGTKLSVKPNIQNPDPAVY QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIP EDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:77;> V28D1J1.1C1 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGLGLRLIYFSYDVKM KEKGDIPEGYSVSREICKERFSLILESASTNQTSMYLCASNRLNTEAFFGQGTRLTVVEDLNKVFPPEVAVFE PSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#49: SEQIDNO:78;> V38.1J49C MTRVSLLWAVVVSTCLESGMAQTVTQSQPEMSVQEAETVTLSCTYDTSENNYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDTAMYFCAFMKNTGNQFYFGTGTSLTVIPNIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:79;> V19D2J2.2C2 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRICEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVN DFQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASRRLDGLGIGELFFGEGSRLTVLEDLKNVFPPEV AVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSA TFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKAT LYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#51: SEQIDNO:80;> V13.1_2J53C MTSIRAVFIFLWLQLDLVNGENVEQHPSTLSVQEGDSAVIKCTYSDSASNYFPWYKQELGKRPQLIIDIRSNV GEKKDQRIAVTLNKTAKHFSLHITETQPEDSAVYFCAALSGGSNYKLTFGKGTLLTVNPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:81;> V14D1J1.1C1 MVSRLLSLVSLCLLGAKHIEAGVTQFPSHSVIEKGQTVTLRCDPISGHDNLYWYRRVMGKEIKFLLHFVKESK QDESGMPNNRFLAERTGGTYSTLKVQPAELEDSGVYFCASSQQENTEAFFGQGTRLTVVEDLNKVFPPEVAVF EPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#52: SEQIDNO:82;> V8.3J54C(AdditionAlMA) MAMLLELIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSPGQGLQLLLKYFS GDTLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGAQGAQKLVFGQGTRLTINPNIQNPDPAVYQL RDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPED TFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:83;> V6.1D2J2.7C2(I> L) MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGT TDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCASSEAGGSSFEQYFGPGTRLTVTEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQNSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#54: SEQIDNO:84;> V9.2J23C MNYSPGLVSLILLLLGRTRGNSVTQMEGPVTLSEEAFLTINCTYTATGYPSLFWYVQYPGEGLQLLLICATKA DDKGSNKGFEATYRKETTSFHLEKGSVQVSDSAVYFCALGRGKLIFGQGTELSVKPNIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPS PESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:85;> V20.1D1J1.1C1(ISLLLPGSLAGmissingfollowingGPG) MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAVDSDLEAFFGQGTRLTVVEDLNKVFPPEVAVFEPSE AEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPR NHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVS ALVLMAMVKRKDF* TCR.sub.CD4-TPT#55: SEQIDNO:86;> V38.2/DV8J34C MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRSAVYNTDKLIFGTGTRLQVFPNIQNPDPAVY QLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIP EDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:87;> V5.1J2.1C2 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQGLQFLFEYFSETQ RNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSFSSYNEQFFGPGTRLTVLEDLKNVFPPEVAVFE PSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#57: SEQIDNO:88;> V8.1J27C MLLLLIPVLGMIFALRDARAQSVSQHNHHVILSEAASLELGCNYSYGGTVNLFWYVQYPGQHLQLLLKYFSGD PLVKGIKGFEAEFIKSKFSFNLRKPSVQWSDTAEYFCAVNARDNAGKSTFGDGTTLTVKPNIQNPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDT FFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:89;> V5.1D2J2.7C2 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQGLQFLFEYFSETQ RNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASRGEPSSYEQYFGPGTRLTVTEDLKNVFPPEVAVF EPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFW QNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#59: SEQIDNO:90;> V39J49C MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQDPGKSLESLFVLLSNGAV KQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDNEFYFGTGTSLTVIPNIQNPDPAVYQLRDSKSSDKS VCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS CDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:91;> V7.9_3D2J2.4C2(S> R) MGTRLLCWMALCLLGADHADTGVSQDPRHKITKRGQNVTFRCDPISEHNRLYWYRQTLGQGPEFLTYFQNEAQ LEKSRLLSDRFSAERPKGSFSTLEIQRTEQGDSAMYLCASSLLGAGNIQYFGAGTRLSVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQNSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYA VLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#67: SEQIDNO:92;> V12.3J9C MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQYSRKGPELLMYTY SSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCALYTGGFKTIFGAGTRLFVKANIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:93;> V5.1D2J2.7C2 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQGLQFLFEYFSETQ RNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSFMGTEQYFGPGTRLTVTEDLKNVFPPEVAVFEP SEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#76: SEQIDNO:94;> V8.3J57C MLLELIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSPGQGLQLLLKYFSGD TLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGAFTRGGSEKLVFGKGMKLTVNPYIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:95;> V19D2_2J2.7C2 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVND FQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCATGSYVGYEQYFGPGTRLTVTEDLKNVFPPEVAVFE PSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#77: SEQIDNO:96;> V14/DV4_3J50C MSLSSLLKVVTASLWLGPGIAQKITQTQPGMFVQEKEAVTLDCTYDTSDPSYGLFWYKQPSSGEMIFLIYQGS YDQQNATEGRYSLNFQKARKSANLVISASQLGDSAMYFCAMREGLAKTSYDKVIFGPGTSLSVIPNIQNPDPA VYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSI IPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:97;> V20.1D2J2.2C2(ISLLLPGSLAGismissingfollowingGPG) MLLLLLLLGPGSGLGAVVSQHPSWVICKSGTSVKIECRSLDFQATTMFWYRQFPKQSLMLMATSNEGSKATYE QGVEKDKFLINHASLTLSTLTVTSAHPEDSSFYICSAPGTGHSAGELFFGEGSRLTVLEDLKNVFPPEVAVFE PSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#78: SEQIDNO:98;> V8.6_2J21C MLLLLVPAFQVIFTLGGTRAQSVTQLDSQVPVFEEAPVELRCNYSSSVSVYLFWYVQYPNQGLQLLLKYLSGS TLVKGINGFEAEFNKSQTSFHLRKPSVHISDTAEYFCAVGPNNFNKFYFGSGTKLNVKPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:99;> V2D1J1.6_2C1(L> I) MDIWLVCWAIFSLLKAGLTEPEVTQTPSHQVTQMGQEVILRCVPISNHLYFYWYRQILGQKVEFLVSFYNNEI SEKSEIFDDQFSVERPDGSNFTLKIRSTKLEDSAMYFCASSPVGGYNSPLHFGNGTRLTVTEDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#79: SEQIDNO:100;> V38.2/DV8J39C MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRSYNAGNMLTFGGGTRLMVKPHIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:101;> V5.1D2J2.1C2 MGSRLLCLVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQGLQFLFEYFSETQ RNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSDTSGGGGEQFFGPGTRLTVLEDLKNVFPPEVAV FEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATF WQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLY AVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#82: SEQIDNO:102;> V38.2/DV8J39C MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQPPSRQMILVIRQEA YKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRSAGLLLTFGGGTRLMVKPHIQNPDPAVYQLR DSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDT FFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:103;> V 19D1J2.7C2 MSNQVLCCVVLCFLGANTVDGGITQSPKYLFRKEGQNVTLSCEQNLNHDAMYWYRQDPGQGLRLIYYSQIVND FQKGDIAEGYSVSREKKESFPLTVTSAQKNPTAFYLCASSKAPGQGNTQGWEQYFGPGTRLTVTEDLKNVFPP EVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRV SATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGK ATLYAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#87: SEQIDNO:104;> V39J31C MKKLLAMILWLQLDRLSGELKVEQNPLFLSMQEGKNYTIYCNYSTTSDRLYWYRQDPGKSLESLFVLLSNGAV KQEGRLMASLDTKARLSTLHITAAVHDLSATYFCAVDMWNNNARLMFGDGTQLVVKPNIQNPDPAVYQLRDSK SSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFP SPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:105;> V5.1J2.6C2 MGSRLLCWVLLCLLGAGPVICAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQGLQFLFEYFSET QRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSLAQSGANVLTFGAGSRLTVLEDLKNVFPPEVA VFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDSRG* TCR.sub.CD4-TPT#91: SEQIDNO:106;> V20_2J53C MEKMLECAFIVLWLQLGWLSGEDQVTQSPEALRLQEGESSSLNCSYTVSGLRGLFWYRQDPGKGPEFLFTLYS AGEEKEKERLKATLTKKESFLHITAPICPEDSATYLCAVLGGSNYKLTFGKGTLLTVNPNIQNPDPAVYQLRD SKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTF FPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:107;> V6.1D1J2.7C2(I> L) MSLGLLCCVAFSLLWASPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHNSMYWYRQDPGMGLRLIYYSASEGT TDKGEVPNGYNVSRLNKREFSLRLESAAPSQTSVYFCAISRDSYEQYFGPGTRLTVTEDLKNVFPPEVAVFEP SEAEISHTQKATLVCLATGFYPDHVELSWWVNGICEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQ NPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAV LVSALVLMAMVKRKDSRG* TCR.sub.CD8-TPT#35/2: SEQIDNO:188;> V19J17C MLTASLLRAVIASICVVSSMAQKVTQAQTEISVVEKEDVTLDCVYETRDTTYYLFWYKQPPSGELVFLIRRNS FDEQNEISGRYSWNFQKSTSSFNFTITASQVVDSAVYFCALIEAAAGNKLTFGGGTRVLVKPNIQNPDPAVYQ LRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPE DTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:189;> V6.2oderV6.3D1J1.2C1(A.fwdarw. V) MSLGLLCCGVFSLLWAGPVNAGVTQTPKFRVLKTGQSMTLLCAQDMNHEYMYWYRQDPGMGLRLIHYSVGEGT TAKGEVPDGYNVSRLKKQNFLLGLESAAPSQTSVYFCASSDGYGYTFGSGTRLTVVEDLNKVFPPEVAVFEPS EAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNP RNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLV SALVLMAMVKRKDF* TCR.sub.CD4-TPT#9: SEQIDNO:190;> V23/DV6J49C MDKILGASFLVLWLQLCWVSGQQKEKSDQQQVKQSPQSLIVQKGGISIINCAYENTAFDYFPWYQQFPGKGPA LLIAIRPDVSEKKEGRFTISFNKSAKQFSLHIMDSQPGDSATYFCAASFYIGNQFYFGTGTSLTVIPNIQNPD PAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNN SIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:191;> V3.1D1J1.2C1(C.fwdarw. T) MGTRLLCCVVFCLLQAGPLDTAVSQTPKYLVTQMGNDKSIKCEQNLGHDTMYWYKQDSKKFLKIMPSYNNKEL IINETVPNRFSPKSPDKAHLNLHINSLELGDSAVYFCASSQEALGGGYGYTFGSGTRLTVVEDLNKVFPPEVA VFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSAT FWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATL YAVLVSALVLMAMVKRKDF* TCR.sub.CD4-TPT#48/2: SEQIDNO:192;> V8.3J43C(E.fwdarw. V) MLLVLIPLLGIHFVLRTARAQSVTQPDIHITVSEGASLELRCNYSYGATPYLFWYVQSPGQGLQLLLKYFSGD TLVQGIKGFEAEFKRSQSSFNLRKPSVHWSDAAEYFCAVGAYDMRFGAGTRLTVKPNIQNPDPAVYQLRDSKS SDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPS PESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS* SEQIDNO:193;> V28D1J1.1C1 MGIRLLCRVAFCFLAVGLVDVKVTQSSRYLVKRTGEKVFLECVQDMDHENMFWYRQDPGLGLRLIYFSYDVKM KEKGDIPEGYSVSREKKERFSLILESASTNQTSMYLCASNRLNTEAFFGQGTRLTVVEDLNKVFPPEVAVFEP SEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQN PRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVL VSALVLMAMVKRKDF* 4.PLAC1-specificTcellreceptors TCR.sub.CD8-mPL#2: SEQIDNO:152;> V6D.6_5J33C(DFSoderDSS.fwdarw. NSF) MNSFPGFVAVILLILGRTHGDSVTQTEGQVTVSESKSLIINCTYSATSIGYPNLFWYVRYPGEGLQLLLKVIT AGQKGSSRGFEATYNKEATSFHLQKASVQESDSAVYYCALSDSNYQLIWGSGTKLIIKPDIQNPEPAVYQLKD PRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSS DVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:153;> V2D1J1.3C1 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQSAKKPLEFMFSYSYQKL MDNQTASSRFQPQSSKKNHLDLQITALKPDDSATYFCASSPDNSGNTLYFGEGSRLIVVEDLRNVTPPKVSLF EPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPR NHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVS TLVVMAMVKRKNS* TCR.sub.CD8-mPL#8: SEQIDNO:154;> V9D.1_1orV9D.1_2J12C(L.fwdarw. F) MLLVFISFLGIHFFLDVQTQTVSQSDAHVTVFEGDSVELRCNYSYGGSIYLSWYIQHHGRGLQFLLKYYSGNP VVQGVNGFKAEFSKSDSSFHLRKASVHWSDSAVYFCAVSAGGYKVVFGSGTRLLVSPDIQNPEPAVYQLKDPR SQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDV PCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:155;> V5D2J2.1C2 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQSAEKPPELMFLYNLKQLI RNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSPGGAEQFFGPGTRLTVLEDLRNVTPPKVSLFEPS KAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHF RCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVSGLV LMAMVKIKKNS* TC12.sub.CD8-mPL#9: SEQIDNO:156;> V4D.4_2J44C(Q.fwdarw. E) MERNLGAVLGILWVQICWVRGDQVEQSPSALSLHEGTGSALRCNFTTTMRAVQWFQQNSRGSLINLFYLASGT KENGRLKSTFNSKESYSTLHIRDAQLEDSGTYFCAAPFVTGSGGKLTLGAGTRLQVNLDIQNPEPAVYQLKDP RSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSD VPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:157;> V2J2.7C2 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQSAKKPLEFMFSYSYQKL MDNQTASSRFQPQSSKKNHLDLQITALKPDDSATYFCASSQDGWGYEQYFGPGTRLTVLEDLRNVTPPKVSLF EPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPR NHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVS GLVLMAMVKKKNS* TCR.sub.CD8-mPL#11: SEQIDNO:158;> V6D.6_2J9_2C(DF.fwdarw. NS) MNSSPGFVAVILLILGRTHGDSVTQTEGPVTVSESESLIINCTYSATSIAYPNLFWYVRYPGEGLQLLLKVIT AGQKGSSRGFEATYNKETTSFHLQKASVQESDSAVYYCALGLGYKLTFGTGTSLLVDPNIQNPEPAVYQLKDP RSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSD VPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:159;> V2D1J1.3C1 MGSIFLSCLAVCLLVAGPVDPKIIQKPKYLVAVTGSEKILICEQYLGHNAMYWYRQSAKKPLEFMFSYSYQKL MDNQTASSRFQPQSSICKNHLDLQITALKPDDSATYFCASSGDNSGNTLYFGEGSRLIVVEDLRNVTPPKVSL FEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNP RNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLV STLVVMAMVKRKNS* TCR.sub.CD8-mPL#12: SEQIDNO:160;> V4D.42J27C(Q.fwdarw. E) MERNLGAVLGILWVQICWVRGDQVEQSPSALSLHEGTGSALRCNFTTTMRAVQWFQQNSRGSLINLFYLASGT KENGRLKSTFNSKESYSTLHIRDAQLEDSGTYFCAAVNTNTGKLTFGDGTVLTVKPNIQNPEPAVYQLKDPRS QDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVP CDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:161;> V30D1J2.2C2 MWTFLLLLWSQGSVFSVLLYQKPNRDICQSGTSLKIQCVADSQVVSMFWYQQFQEQSLMLMATANEGSEATYE SGFTKDKFPISRPNLTFSTLTVNNARPGDSSIYFCSSRTPNTGQLYFGEGSKLTVLEDLRNVTPPKVSLFEPS KAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHF RCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVSGLV LMAMVKKKNS* TCR.sub.CD8-mPL#14: SEQIDNO:162;> V9D.1_2J12C MLLVLISFLGIHFFLDVQTQTVSQSDAHVTVFEGDSVELRCNYSYGGSIYLSWYIQHHGHGLQFLLKYYSGNP VVQGVNGFEAEFSKSDSSFHLRKASVHWSDSAVYFCAVSSGGYKVVFGSGTRLLVSPDIQNPEPAVYQLKDPR SQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDV PCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:163;> V5D1J1.1C1 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQSAEKPPELMFLYNLKQLI RNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSQGGTEVFFGKGTRLTVVEDLRNVTPPKVSLFEPS KAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHF RCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLV VMAMVKRKNS* TCR.sub.CD8-mPL#17: SEQIDNO:164;> V14.1J31_1oder_2C MDKILTATFLLLGLHLAGVNGQQQEKRDQQQVRQSPQSLTVWEGETAILNCSYEDSTFNYFPWYQQFPGEGPA LLISIRSVSDKKEDGRFTIFFNKREKKLSLHITDSQPGDSATYFCAPNNRIFFGDGTQLVVKPNIQNPEPAVY QLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNAT YPSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:165;> V13.2D2J2.1C2 MGSRLFFVLSSLLCSKHMEAAVTQSPRNKVAVTGGKVTLSCNQTNNHNNMYWYRQDTGHGLRLIHYSYGAGST EKGDIPDGYKASRPSQENFSLILELATPSQTSVYFCASLGYNYAEQFFGPGTRLTVLEDLRNVTPPKVSLFEP SKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNH FRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVSGL VLMAMVKKKNS* TCR.sub.CD8-mPL#19: SEQIDNO:166;> V6D.3J22C MNNSPALVTVMLFILGRTHGDSVIQMQGQVTLSENDFLFINCTYSTTGYPTLFWYVQYSGEGPQLLLQVTTAN NKGSSRGFEATYDKGTTSFHLQKTSVQEIDSAVYYCAMSDASGSWQLIFGSGTQLTVMPDIQNPEPAVYQLKD PRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSS DVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:167;> V13.3D1J1.6C1 MGSRLFFVVLILLCAKHMEAAVTQSPRSKVAVTGGKVTLSCHQTNNHDYMYWYRQDTGHGLRLIHYSYVADST EKGDIPDGYKASRPSQENFSLILELASLSQTAVYFCASSPDRPSYNSPLYFAAGTRLTVTEDLRNVTPPKVSL FEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNP RNHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLV STLVVMAMVKRKNS* TCR.sub.CD8-mPL#20: SEQIDNO:168;> V12.3_3J38C MRPGTCSVLVLLLMLRRSNGDGDSVTQKEGLVTLTEGLPVMLNCTYQTIYSNAFLFWYVHYLNESPRLLLKSS TDNKRTEHQGFHATLHKSSSSFHLQKSSAQLSDSALYYCALNNVGDNSKLIWGLGTSLVVNPNIQNPEPAVYQ LKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATY PSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:169;> V5D2J1.1C1 MSCRLLLYVSLCLVETALMNTKITQSPRYLILGRANKSLECEQHLGHNAMYWYKQSAEKPPELMFLYNLKQLI RNETVPSRFIPECPDSSKLLLHISAVDPEDSAVYFCASSQYGGANTEVFFGKGTRLTVVEDLRNVTPPKVSLF EPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPR NHFRCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVS TLVVMAMVKRKNS* TCR.sub.CD8-mPL#22: SEQIDNO:170;> V 13D.2J34_2C(V.fwdarw. L) MKRLLCSLLGLLCTQVCWVKGQQVQQSPASLVLQEGENAELQCNFSSTATRLQWFYQHPGGRLVSLFYNPSGT KHTGRLTSTTVTNERRSSLHISSSQTTDSGTYFCAAASNTNKVVFGTGTRLQVLPNIQNPEPAVYQLKDPRSQ DSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPC DATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:171;> V20D1J2.1C2 MLLLLLLLGPGCGLGALVYQYPRRTICKSGTSMRMECQAVGFQATSVAWYRQSPQKTFELIALSTVNSAIKYE QNFTQEKFPISHPNLSFSSMTVLNAYLEDRGLYLCGVDRANYAEQFFGPGTRLTVLEDLRNVTPPKVSLFEPS KAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHF RCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVSGLV LMAMVKKKNS* TCR.sub.CD8-mPL#25: SEQIDNO:194;> V8.1_3J21C MHSLLGLLLWLQLTRVNSQLAEENSWALSVHEGESVTVNCSYKTSITALQWYRQKSGKGPAQLILIRSNEREK RNGRLRATLDTSSQSSSLSITATRCEDTAVYFCATDNVLYFGSGTKLTVEPNIQNPEPAVYQLKDPRSQDSTL CLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSNGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATL TEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS* SEQIDNO:195;> V31D2J2.1C2 MLYSLLAFLLGMFLGVSAQTIHQWPVAEIKAVGSPLSLGCTIKGKSSPNLYWYWQATGGTLQQLFYSITVGQV ESVVQLNLSASRPKDDQFILSTEKLLLSHSGFYLCAWKLGNYAEQFFGPGTRLTVLEDLRNVTPPKVSLFEPS KAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTDPQAYKESNYSYCLSSRLRVSATFWHNPRNHF RCQVQFHGLSEEDKWPEGSPKPVTQNISAEAWGRADCGITSASYHQGVLSATILYEILLGKATLYAVLVSGLV LMAMVKKKNS*