Peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers

Abstract

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Claims

1. A method of treating a patient who has cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of EAMKRLSYI (SEQ ID NO: 157), wherein the cancer is ovarian cancer, cholangiocellular carcinoma, head and neck squamous cell carcinoma, or pancreatic cancer.

2. The method of claim 1, wherein the T cells are autologous to the patient.

3. The method of claim 1, wherein the T cells are obtained from a healthy donor.

4. The method of claim 1, wherein the population of activated T cells are administered in the form of a composition, wherein the composition further comprises an adjuvant.

5. The method of claim 4, wherein the adjuvant is selected from anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

6. The method of claim 1, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

7. The method of claim 6, wherein the antigen presenting cell is infected with a recombinant virus expressing the peptide.

8. The method of claim 1, wherein the cancer is ovarian cancer.

9. The method of claim 1, wherein the cancer is cholangiocellular carcinoma.

10. The method of claim 1, wherein the cancer is head and neck squamous cell carcinoma.

11. The method of claim 1, wherein the cancer is pancreatic cancer.

12. A method of eliciting an immune response in a patient who has cancer, comprising administering to said patient a population of activated T cells that kill cancer cells that present a peptide consisting of the amino acid sequence of EAMKRLSYI (SEQ ID NO: 157), wherein the cancer is ovarian cancer, cholangiocellular carcinoma, head and neck squamous cell carcinoma, or pancreatic cancer.

13. The method of claim 12, wherein the activated T cells are cytotoxic T cells produced by contacting T cells with an antigen presenting cell that expresses the peptide in a complex with an MHC class I molecule on the surface of the antigen presenting cell, for a period of time sufficient to activate said T cell.

14. The method of claim 12, wherein the T cells are autologous to the patient.

15. The method of claim 12, wherein the T cells are obtained from a healthy donor.

16. The method of claim 12, wherein the population of activated T cells are administered in the form of a composition, wherein the composition further comprises an adjuvant selected from anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

17. The method of claim 12, wherein the cancer is ovarian cancer.

18. The method of claim 12, wherein the cancer is cholangiocellular carcinoma.

19. The method of claim 12, wherein the cancer is head and neck squamous cell carcinoma.

20. The method of claim 12, wherein the cancer is pancreatic cancer.

Description

FIGURES

(1) FIGS. 1A through 1S show exemplary expression profile of source genes of the present invention that are over-expressed in different cancer samples. Tumor (black dots) and normal (grey dots) samples are grouped according to organ of origin, and box-and-whisker plots represent median, 25th and 75th percentile (box), and minimum and maximum (whiskers) RPKM values. Normal organs are ordered according to risk categories. RPKM=reads per kilobase per million mapped reads. Normal samples: blood cells; blood vessel; brain; heart; liver; lung; adipose: adipose tissue; adren. gl.: adrenal gland; bile duct; bladder; BM: bone marrow; cartilage; esoph: esophagus; eye; gallb: gallbladder; head and neck; kidney; large_int: large intestine; LN: lymph node; nerve; pancreas; parathyr: parathyroid; pituit: pituitary; skel. mus: skeletal muscle; skin; small_int: small intestine; spleen; stomach; thyroid; trachea; bladder; breast; ovary; placenta; prostate; testis; thymus; uterus. Tumor samples: AML: acute myeloid leukemia: BRCA: breast cancer; CLL: chronic lymphocytic leukemia; CRC: colorectal cancer; GALB: gallbladder cancer; GB: glioblastoma; GC: gastric cancer; HCC: hepatocellular carcinoma; HNSCC: head-and-neck cancer; MEL: melanoma; NHL: non-hodgkin lymphoma; NSCLC: non-small cell lung cancer; OC: ovarian cancer; OSC_GC: esophageal/gastric cancer; OSCAR: esophageal cancer; PC: pancreatic cancer; PCA: prostate cancer; RCC: renal cell carcinoma; SCLC: small cell lung cancer; UBC: urinary bladder carcinoma; UEC: uterine and endometrial cancer. FIG. 1A) Gene symbol: CT45A2, Peptide: KYEKIFEML (SEQ ID No.: 12), FIG. 1B) Gene symbol: NLRP2, Peptide: VLYGPAGLGK (SEQ ID No.: 27), FIG. 1C) Gene symbol: NLRP7, Peptide: LLDEGAMLLY (SEQ ID No.: 31), FIG. 1D) Gene symbol: HTR3A, Peptide: GLLQELSSI (SEQ ID No.: 66), FIG. 1E) Gene symbol: VTCN1, Peptide: KVVSVLYNV (SEQ ID No.: 75), FIG. 1F) Gene symbol: CYP2W1, Peptide: RYGPVFTV (SEQ ID No.: 98), FIG. 1G) Gene symbol: MMP11, Peptide: LLQPPPLLAR (SEQ ID No.: 98), FIG. 1H) Gene symbol: MMP12, Peptide: FVDNQYWRY (SEQ ID No.: 115), FIG. 1I) Gene symbol: CTAG2, Peptide: APLPRPGAVL (SEQ ID No.: 119), FIG. 1J) Gene symbol: FAM111B, Peptide: KPSESIYSAL (SEQ ID No.: 123), FIG. 1K) Gene symbol: CCNA1, Peptide: HLLLKVLAF (SEQ ID No.: 151), FIG. 1L) Gene symbol: FAM83H, Peptide: HVKEKFLL (SEQ ID No.: 156), FIG. 1M) Gene symbol: MAGEA11, Peptide: KEVDPTSHSY (SEQ ID No.: 194), FIG. 1N) Gene symbol: MMP11, Peptide: YTFRYPLSL (SEQ ID No.: 227), FIG. 1O) Gene symbol: ZNF560, Peptide: VFVSFSSLF (SEQ ID No.: 255), FIG. 1P) Gene symbol: IGF2BP1, Peptide: ISYSGQFLVK (SEQ ID No.: 266), FIG. 1Q) Gene symbol: CLDN6, Peptide: LPMWKVTAF (SEQ ID No.: 303), FIG. 1R) Gene symbol: IGF2BP3, Peptide: IEALSGKIEL (SEQ ID No.: 413), FIG. 1S) Gene symbol: PRAME, Peptide: EEQYIAQF (SEQ ID No.: 432).

(2) FIGS. 1T through 1V show exemplary expression profiles of source genes of the present invention, that are over-expressed in different cancer samples. Tumor (black dots) and normal (grey dots) samples are grouped according to organ of origin. Box-and-whisker plots represent median FPKM value, 25th and 75th percentile (box) plus whiskers that extend to the lowest data point still within 1.5 interquartile range (IQR) of the lower quartile and the highest data point still within 1.5 IOR of the upper quartile. Normal organs are ordered according to risk categories. FPKM: fragments per kilobase per million mapped reads. Normal samples: blood cells; bloodvess (blood vessels); brain; heart; liver, lung; adipose (adipose tissue); adrenal gl (adrenal gland); bile duct; bladder, bone marrow; cartilage; esoph (esophagus); eye; gall bl (gallbladder); head&neck; intest. la (large intestine); intest. sm (small intestine); kidney; lymph node; nerve perith (peripheral nerve); pancreas; parathyr (parathyroid gland); pent (peritoneum); pituit (pituitary); pleura; skel. mus (skeletal muscle); skin; spleen; stomach; thyroid; trachea; ureter, breast; ovary; placenta; prostate; testis; thymus; uterus. Tumor samples: AML (acute myeloid leukemia); BRCA (breast cancer); CCC (cholangiocellular carcinoma); CLL (chronic lymphocytic leukemia); CRC (colorectal cancer); GBC (gallbladder cancer); GBM (glioblastoma); GC (gastric cancer); HCC (hepatocellular carcinoma); HNSCC (head and neck squamous cell carcinoma); MEL (melanoma); NHL (non-hodgkin lymphoma); NSCLCadeno (non-small cell lung cancer adenocarcinoma); NSCLCother (NSCLC samples that could not unambiguously be assigned to NSCLCadeno or NSCLCsquam); NSCLCsquam (squamous cell non-small cell lung cancer); OC (ovarian cancer); OSCAR (esophageal cancer); PACA (pancreatic cancer); PRCA (prostate cancer); RCC (renal cell carcinoma); SCLC (small cell lung cancer); UBC (urinary bladder carcinoma); UEC (uterine and endometrial cancer). FIG. 1T) Gene symbol: MAGEA4, Peptide: SPDAESLFREALSNKVDEL (SEQ ID No.: 597), FIG. 1U) Gene symbol: MAGEA4, Peptide: LSNKVDELAHFLLRK (SEQ ID No.: 601), FIG. 1V) Gene symbol: MAGEB3, Peptide: KLITQDLVKLKYLEYRQ (SEQ ID No.: 604).

(3) FIG. 2 shows exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*02+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*02 in complex with SeqiD No 773 peptide (ALYGKLLKL, Seq ID NO: 773) (left panel. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*02/SeqID No 773. Right panel shows control staining of cells stimulated with irrelevant A*02/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(4) FIG. 3 shows exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*24+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*24 in complex with SeqiD No 774 peptide (left panel). After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*24/SeqID No 774 (VYVDDIYVI, Seq ID NO: 774). Right panel shows control staining of cells stimulated with irrelevant A*24/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(5) FIGS. 4A and 4B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*02+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*02 in complex with SeqiD No 67 peptide SLLLPSIFL (FIG. 4A, left panel) and SeqiD No 75 peptide KWSVLYNV (FIG. 4B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*02/SeqID No 67 (FIG. 4A) or A*02/SeqID No 75 (FIG. 4B). Right panels (FIGS. 4A and 4B) show control staining of cells stimulated with irrelevant A*02/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(6) FIGS. 5A and 5B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*24+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*24 in complex with SeqiD No 11 peptide SYSDLHYGF (FIG. 5A, left panel) and SeqiD No 79 peptide SYNEHWNYL (FIG. 5B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*24/SeqID No 11 (FIG. 5A) or A*24/SeqID No 79 (FIG. 5B). Right panels (FIGS. 5A and 5B) show control staining of cells stimulated with irrelevant A*24/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(7) FIGS. 6A and 6B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-B*07+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-B*07 in complex with SeqiD No 33 peptide SPTFHLTL (FIG. 6A, left panel) and SeqiD No 40 peptide KPGTSYRVTL (FIG. 6B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with B*07/SeqID No 33 (FIG. 6A) or B*07/SeqID No 40 (FIG. 6B). Right panels (FIGS. 6A and 6B) show control staining of cells stimulated with irrelevant B*07/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(8) FIGS. 7A and 7B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*01+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*01 in complex with SeqiD No 113 peptide QLDSNRLTY (FIG. 7A, left panel) and SeqiD No 115 peptide FVDNQYWRY (FIG. 7B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*01/SeqID No 113 (FIG. 7A) or A*01/SeqID No 115 (FIG. 7B). Right panels (FIGS. 7A and 7B) show control staining of cells stimulated with irrelevant A*01/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(9) FIGS. 8A and 8B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-A*03+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-A*03 in complex with SeqiD No 23 peptide GMMKGGIRK (FIG. 8A, left panel) and SeqiD No 90 peptide KVAGERYVYK (FIG. 8B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with A*03/SeqID No 23 (FIG. 8A) or A*03/SeqID No 90 (FIG. 8B). Right panels (FIGS. 8A and 8B) show control staining of cells stimulated with irrelevant A*03/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

(10) FIGS. 9A and 9B show exemplary results of peptide-specific in vitro CD8+ T cell responses of a healthy HLA-B*44+ donor. CD8+ T cells were primed using artificial APCs coated with anti-CD28 mAb and HLA-B*44 in complex with SeqiD No 200 peptide AESIPTVSF (FIG. 9A, left panel) and SeqiD No 211 peptide EEKVFPSPLW (FIG. 9B, left panel), respectively. After three cycles of stimulation, the detection of peptide-reactive cells was performed by 2D multimer staining with B*44/SeqID No 200 (FIG. 9A) or B*44/SeqID No 211 (FIG. 9B). Right panels (FIGS. 9A and 9B) show control staining of cells stimulated with irrelevant B*44/peptide complexes. Viable singlet cells were gated for CD8+ lymphocytes. Boolean gates helped excluding false-positive events detected with multimers specific for different peptides. Frequencies of specific multimer+ cells among CD8+ lymphocytes are indicated.

EXAMPLES

Example 1

(11) Identification of Tumor Associated Peptides Presented on the Cell Surface

(12) Tissue Samples

(13) Patients' tumor tissues and normal tissues were obtained from the University Hospital Tübingen (Tubingen, Germany). Written informed consents of all patients had been given before surgery or autopsy. Tissues were shock-frozen immediately after excision and stored until isolation of TUMAPs at −70° C. or below.

(14) Isolation of HLA Peptides from Tissue Samples

(15) HLA peptide pools from shock-frozen tissue samples were obtained by immune precipitation from solid tissues according to a slightly modified protocol (Falk et al., 1991; Seeger et al., 1999) using the HLA-A*02-specific antibody BB7.2, the HLA-A, -B, C-specific antibody W6/32, the HLA-DR specific antibody L243 and the pan-HLA class II specific antibody Tü39, CNBr-activated sepharose, acid treatment, and ultrafiltration.

(16) Mass Spectrometry Analyses

(17) The HLA peptide pools as obtained were separated according to their hydrophobicity by reversed-phase chromatography (Ultimate 3000 RSLC Nano UHPLC System, Dionex)) and the eluting peptides were analyzed in LTQ-Orbitrap and Fusion Lumos hybrid mass spectrometers (ThermoElectron) equipped with an ESI source. Peptide samples were loaded with 3% of solvent B (20% H.sub.2O, 80% acetonitrile and 0.04% formic acid) on a 2 cm PepMap 100 C18 Nanotrap column (Dionex) at a flowrate of 4 μl/min for 10 min. Separation was performed on either 25 cm or 50 cm PepMap C18 columns with a particle size of 2 μm (Dionex) mounted in a column oven running at 50° C. The applied gradient ranged from 3 to 32% solvent B within 90 min at a flow rate of 300 nl/min (for 25 cm columns) or 140 min at a flow rate of 175 nl/min (for 50 cm columns). (Solvent A: 99% H.sub.2O, 1% ACN and 0.1% formic acid; Solvent B: 20% H.sub.2O, 80% ACN and 0.1% formic acid).

(18) Mass spectrometry analysis was performed in data dependent acquisition mode employing a top five method (i.e. during each survey scan the five most abundant precursor ions were selected for fragmentation). Alternatively, a TopSpeed method was employed for analysis on Fusion Lumos instruments,

(19) Survey scans were recorded in the Orbitrap at a resolution of 60,000 (for Orbitrap XL) or 120,000 (for Orbitrap Fusion Lumos). MS/MS analysis was performed by collision induced dissociation (CID, normalized collision energy 35%, activation time 30 ms, isolation width 1.3 m/z) with subsequent analysis in the linear trap quadrupole (LTQ). Mass range for HLA class I ligands was limited to 400-650 m/z with possible charge states 2+ and 3+ selected for fragmentation. For HLA class II mass range was set to 300-1500 m/z allowing for fragmentation with all positive charge states ≥2.

(20) Tandem mass spectra were interpreted by MASCOT or SEQUEST at a fixed false discovery rate (q≤0.05) and additional manual control. In cases where the identified peptide sequence was uncertain it was additionally validated by comparison of the generated natural peptide fragmentation pattern with the fragmentation pattern of a synthetic sequence-identical reference peptide.

(21) Table 19 shows the presentation on various cancer entities for selected peptides, and thus the particular relevance of the peptides as mentioned for the diagnosis and/or treatment of the cancers as indicated (e.g. peptide SEQ ID No. 1 for colorectal cancer, gallbladder cancer, non-hodgkin lymphoma, non-small cell lung cancer, and uterine and endometrial cancer, peptide SEQ ID No. 2 for breast cancer, cholangiocellular carcinoma, colorectal cancer, gallbladder cancer, gastric cancer, head and neck squamous cell carcinoma, melanoma, non-hodgkin lymphoma, non-small cell lung cancer, esophageal cancer, pancreatic cancer, prostate cancer, renal cell carcinoma, small cell lung cancer, and uterine and endometrial cancer).

(22) TABLE-US-00010 TABLE 19 Overview of presentation of selected tumor-associated peptides of the present invention across tumor types. AML: acute myeloid leukemia; BRCA: breast cancer; CCC: cholangiocellular carcinoma; CLL: chronic lymphocytic leukemia; CRC: colorectal cancer; GBC: gallbladder cancer; GBM: glioblastoma; GC: gastric cancer; GEJC: gastro-esophageal junction cancer; HCC: hepatocellular carcinoma; HNSCC: head and neck squamous cell carcinoma; MEL: melanoma; NHL: non-hodgkin lymphoma; NSCLC: non-small cell lung cancer; OC: ovarian cancer; OSCAR: esophageal cancer; PACA: pancreatic cancer; PRCA: prostate cancer; RCC: renal cell carcinoma; SCLC: small cell lung cancer; UBC: urinary bladder carcinoma; UEC: uterine and endometrial cancer Seq Peptide Presentation on ID No Sequence tumor types 1 MIPTFTALL CRC, GBC, NHL, NSCLC, UEC 2 TLLKALLEI BRCA, CCC, CRC, GBC, GC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UEC 3 ALIYNLVGI HCC 4 ALFKAWAL AML, BRCA, CLL, CRC, GBC, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, RCC, SCLC, UBC, UEC 5 RLLDFINVL UEC 7 ALQAFEFRV GC, GEJC, HNSCC, NSCLC, PACA, SCLC, UBC 8 YLVTKVVAV AML, BRCA, CCC, CLL, CRC, GBC, GBM, GC, GEJC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 10 RYSDSVGRVSF BRCA, CRC, GBC, GC, NSCLC, SCLC, UBC, UEC 11 SYSDLHYGF GC, NSCLC, UEC 12 KYEKIFEML AML, NSCLC 13 VYTFLSSTL NSCLC 14 FYFPTPTVL GBC, NSCLC 15 VYHDDKQPTF GBM, GC, NSCLC, OSCAR, UEC 16 IYSPQFSRL BRCA, NHL, NSCLC, OSCAR, UBC, UEC 18 KYPVHIYRL AML, BRCA, GBC, GC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, RCC, UBC, UEC 19 KYVKVFHQF AML, BRCA, CLL, CRC, GBC, GBM, GC, HCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 20 RMASPVNVK CLL 21 AVRKPIVLK AML, BRCA, CCC, CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, RCC, SCLC, UBC, UEC 22 SLKERNPLK NSCLC 24 SMYYPLQLK BRCA, CRC, GBM, HCC, NHL, RCC 25 GTSPPSVEK UEC 27 VLYGPAGLGK HCC, HNSCC, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 28 KTYETNLEIKK NSCLC, UBC 29 QQFLTALFY PACA, PRCA 31 LLDEGAMLLY GBC, HNSCC, NSCLC, SCLC, UBC 32 SPNKGTLSV NSCLC 33 SPTFHLTL NSCLC, PRCA, SCLC, UBC, UEC 34 LPRGPLASLL HNSCC, NSCLC, OSCAR, PACA, SCLC 35 FPDNQRPAL BRCA, CRC, GBC, MEL, NSCLC, PACA, UBC, UEC 36 APAAWLRSA BRCA, CCC, CRC, GBC, GC, HCC, HNSCC, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 38 SPHPVTALLTL PACA, UEC 40 KPGTSYRVTL GBM 43 ALKARTVTF BRCA, CCC, GBM, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PRCA, SCLC, UBC, UEC 48 DVKKKIKEV NSCLC, RCC, SCLC 53 MEHPGKLLF UEC 56 SEPDTTASW NSCLC, UEC 57 QESDLRLFL BRCA, CLL, CRC, GC, GEJC, HNSCC, NHL, NSCLC, PACA, UBC, UEC 59 SENVTMKVV UEC 60 GLLSLTSTLYL BRCA 62 KVLGVNVML BRCA, HNSCC, MEL, NSCLC, SCLC 63 MMEEMIFNL UBC 64 FLDPDRHFL BRCA, CCC, CRC, GBC, GC, GEJC, HCC, HNSCC, MEL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 65 TMFLRETSL MEL, NHL, NSCLC, PRCA, SCLC 68 KLFDTQQFL AML, BRCA, CRC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, RCC 69 TTYEGSITV NSCLC, UEC 71 YLEDTDRNL AML, BRCA, CCC, CRC, GBC, GC, GEJC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 72 YLTDLQVSL AML, BRCA, CCC, CLL, CRC, GBC, GBM, GC, GEJC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 74 SQSPSVSQL UEC 75 KVVSVLYNV BRCA, UEC 77 RYGPVFTV CCC, GC 78 SFAPRSAVF SCLC 79 SYNEHWNYL BRCA, CCC, CRC, GBC, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 81 VYNHTTRPL OSCAR 85 VLLGSLFSRK AML, CRC, HCC, MEL, NHL, NSCLC, RCC, UEC 86 VVLLGSLFSRK AML, CRC, GC, HCC, PACA, RCC 87 AVAPPTPASK AML, CRC, GBC, MEL, NSCLC, OSCAR, RCC, SCLC, UEC 90 KVAGERYVYK CCC, UEC 92 SVFPIENIY UEC 94 ATFERVLLR BRCA, NSCLC 96 TAFGGFLKY OSCAR, RCC 97 TMLDVEGLFY GC 99 KVVDRWNEK CRC, NHL, RCC 101 RVFTSSIKTK NSCLC, PACA, UEC 106 AAFVPLLLK AML, BRCA, NHL, NSCLC, SCLC 108 VLYPVPLESY AML, MEL, NHL, NSCLC, RCC, SCLC, UEC 109 KTFTIKRFLAK BRCA, CCC, MEL, NHL, NSCLC, OSCAR, SCLC, UEC 110 SAAPPSYFR RCC, UEC 113 QLDSNRLTY HCC 115 FVDNQYWRY BRCA, GBC, GC, GEJC, NSCLC, OSCAR, PACA, SCLC 116 VLLDEGAMLLY NSCLC, PACA 117 APRLLLLAVL BRCA, CRC, HNSCC, MEL, NSCLC, OSCAR, PRCA, RCC, SCLC, UBC, UEC 118 SPASRSISL NHL, OSCAR, RCC 119 APLPRPGAVL MEL, OSCAR 120 RPAMNYDKL CRC 123 KPSESIYSAL BRCA, CRC, HNSCC, MEL, NHL, NSCLC, OSCAR, SCLC, UBC 124 LPSDSHFKITF CRC, HNSCC, NHL, OSCAR, SCLC 125 VPVYILLDEM CCC, GC, HNSCC, UEC 127 APRAGSQVV AML, BRCA, CRC, GBM, HCC, HNSCC, MEL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 129 APRPASSL BRCA, CRC, NSCLC, OSCAR, SCLC, UEC 133 MPNLPSTTSL UEC 141 SPMTSLLTSGL UEC 146 IPRPEVQAL AML, CRC, GC, HNSCC, MEL 147 APRWFPQPTVV BRCA 148 KPYGGSGPL AML, BRCA, NHL, RCC 149 GPREALSRL AML, BRCA, CCC, CRC, HCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UEC 150 MAAVKQAL CCC, NSCLC, PACA 151 HLLLKVLAF HNSCC 152 MGSARVAEL HNSCC 156 HVKEKFLL CCC, HNSCC 157 EAMKRLSYI CCC, HNSCC, PACA 174 AEATARLNVF NSCLC 176 AEIEPKADGSW CCC, NSCLC, PRCA 178 NELFRDGVNW AML, BRCA, CCC, CLL, CRC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, SCLC, UBC, UEC 179 REAGDEFEL CCC, NSCLC, SCLC 180 REAGDEFELRY CRC, HCC, MEL, NSCLC, OSCAR, PACA, RCC, UEC 181 GEGPKTSW NSCLC 182 KEATEAQSL NSCLC 184 AELEALTDLW NHL, NSCLC, NSCLC 186 REGPEEPGL GC 188 AEFAKKQPWW CCC, CLL, CRC, MEL, NHL, NSCLC 191 EEDAALFKAW AML, BRCA, CCC, CLL, CRC, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 192 YEFKFPNRL BRCA, HCC, NSCLC, OSCAR, UEC 196 REMPGGPVW BRCA, CCC, CRC, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 197 AEVLLPRLV NSCLC, PACA, UEC 199 REIDESLIFY NSCLC 200 AESIPTVSF NSCLC 208 TEVSRTEAI NSCLC, UEC 211 EEKVFPSPLW NHL 215 SEDGLPEGIHL CLL, GC, GEJC, HNSCC, NHL, NSCLC, PACA 216 IMFDDAIERA UEC 217 VSSSLTLKV BRCA, RCC 224 SLPRFQVTL BRCA, HCC, NHL, NSCLC, OSCAR, UBC, UEC 225 SVFAHPRKL BRCA, OSCAR 226 QVDPKKRISM BRCA, NHL, NSCLC, SCLC 227 YTFRYPLSL CCC, CRC, GBC, GC, HCC, HNSCC, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 228 RLWDWVPLA AML, NHL 235 SAIETSAVL NSCLC, UEC 237 SAMGTISIM UEC 240 FSTDTSIVL PACA 241 RQPNILVHL UEC 243 YASEGVKQV UEC 245 LAVEGGQSL AML, BRCA, CCC, CRC, GBC, GBM, GC, GEJC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 246 RYLAVVHAVF HCC, NHL, NSCLC, PACA, SCLC 247 ARPPWMWVL BRCA, GBC, HNSCC, OSCAR 251 KQRQVLIFF GBM, NSCLC, OSCAR, PACA, RCC 252 LYQPRASEM NHL 256 RTEEVLLTFK RCC, SCLC, UEC 257 VTADHSHVF UEC 259 KTLELRVAY GBC, HNSCC 260 GTNTVILEY MEL, PACA, UEC 262 RSRLNPLVQR HNSCC, NSCLC 264 AIKVIPTVFK HNSCC, MEL, NSCLC, RCC, UEC 268 GLLGLSLRY PRCA 269 RLKGDAWVYK MEL, NHL, OSCAR, UEC 271 RMFADDLHNLNK NSCLC 273 RVNAIPFTY GBC 275 STTFPTLTK UEC 277 TTALKTTSR NSCLC 279 SVSSETTKIKR UEC 280 SVSGVKTTF HCC, UEC 281 RAKELEATF CLL, GC, NSCLC 283 IVQEPTEEK HCC, NHL, NSCLC 286 TVAPPQGVVK HCC 288 SPVTSVHGGTY NHL 289 RWEKTDLTY CRC, UEC 291 ETIRSVGYY GBM, NSCLC, UBC 295 YPLRGSSIFGL UEC 296 YPLRGSSI UEC 299 HPGSSALHY AML, CCC, CRC, GC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, UEC 300 IPMAAVKQAL AML, BRCA, CLL, CRC, GC, HCC, HNSCC, MEL, NSCLC, OSCAR, PACA, RCC, UEC 302 RVEEVRALL BRCA, CRC, GBM, UBC 306 APVIFSHSA AML, CCC, HCC, MEL, NSCLC, UBC 307 LPYGPGSEAAAF BRCA, UEC 308 YPEGAAYEF PRCA, UEC 314 VPDQPHPEI PACA 315 SPRENFPDTL HNSCC 317 FPFQPGSV AML, BRCA, CLL, CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 318 FPNRLNLEA CCC, CLL, GC, HNSCC, MEL, NSCLC, PRCA, RCC, SCLC, UBC 319 SPAEPSVYATL BRCA, GC, NSCLC, OSCAR 320 FPMSPVTSV AML, BRCA, CCC, CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 321 SPMDTFLLI AML, BRCA, CLL, CRC, GBC, GBM, GC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, SCLC, UBC, UEC 322 SPDPSKHLL NHL, NSCLC, PRCA, RCC 324 VPYRVVGL CLL, CRC, GC, MEL, NHL, NSCLC, PRCA, SCLC 325 GPRNAQRVL CRC, GBC, NHL, NSCLC 326 VPSEIDAAF BRCA, CCC, CRC, GBC, GC, NSCLC, OSCAR, PACA, RCC, SCLC, UEC 330 FPFVTGSTEM UEC 331 FPHPEMTTSM UEC 332 FPHSEMTTL NSCLC, PACA 333 FPHSEMTTVM NSCLC, SCLC, UEC 334 FPYSEVTTL NSCLC, SCLC, UEC 335 HPDPVGPGL NSCLC, UEC 337 HPVETSSAL UEC 355 SPLVTSHIM UEC 363 TAKTPDATF CCC 369 FPHSEMTTV PACA, UEC 371 LYVDGFTHW NSCLC, UEC 376 RPRSPAGQVA PACA 378 RPRSPAGQVAA NHL, PACA, SCLC 385 SPALHIGSV BRCA, GBM, HCC, NSCLC, PRCA, SCLC, UBC, UEC 386 FPFNPLDF GC, NHL 388 SPAPLKLSRTPA MEL 389 SPGAQRTFFQL AML, MEL 391 APSTPRITTF HCC, NHL 392 KPIESTLVA GBM, MEL, NSCLC, UEC 393 ASKPHVEI CRC 395 VLLPRLVSC NSCLC 399 RELLHLVTL NSCLC, SCLC, UEC 403 EEAQWVRKY BRCA, CLL, NHL 404 NEAIMHQY BRCA, CCC, CLL, CRC, GBC, GC, HCC, MEL, NHL, NSCLC, OSCAR, SCLC, UBC, UEC 405 NEIWTHSY NSCLC, UEC 407 AEHEGVSVL NSCLC, UEC 408 LEKALQVF CRC, GC, HNSCC, OSCAR, UEC 409 REFVLSKGDAGL GBC, GC, GEJC, HNSCC, NSCLC 410 SEDPSKLEA BRCA, HNSCC, NSCLC, OSCAR, SCLC, UEC 411 LELPPILVY BRCA, CRC, GBC, GBM, GC, NHL, NSCLC, OSCAR, PRCA, SCLC, UBC, UEC 414 EDAALFKAW CLL, CRC, MEL, NHL 415 REEDAALFKAW BRCA, CLL, CRC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PRCA, UBC, UEC 416 SEEETRVVF AML, CRC, HNSCC, NSCLC, UEC 417 AEHFSMIRA AML, BRCA, CRC, GBM, GC, HNSCC, NHL, NSCLC, OSCAR, PACA, PRCA, RCC, UEC 418 FEDAQGHIW BRCA, CCC, CRC, HCC, NSCLC, OSCAR, PACA, UBC, UEC 419 HEFGHVLGL BRCA, CCC, CRC, GC, HNSCC, MEL, NSCLC, OSCAR, PACA, UEC 420 FESHSTVSA UEC 423 SEVPTGTTA GBC, GBM 425 SEVPLPMAI NSCLC, UEC 429 REKFIASVI UEC 430 DEKILYPEF UEC 431 AEQDPDELNKA CRC, OSCAR, SCLC, UEC 432 EEQYIAQF OSCAR, SCLC 433 SDSQVRAF GBM, GC, HCC, HNSCC, NSCLC, OSCAR, RCC, SCLC, UEC 436 REPGDIFSEL CRC 437 TEAVVTNEL CRC, GC, NSCLC, SCLC, UEC 438 SEVDSPNVL CCC, CLL, CRC, GC, HNSCC, MEL, NHL, NSCLC, SCLC, UBC 442 ILSKLTDIQY BRCA, GBM, NHL, NSCLC 443 GTFNPVSLW BRCA, GBC, GBM, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, SCLC 444 KLSQKGYSW BRCA, CCC, CRC, GBM, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, SCLC, UBC 445 LHITPGTAY HCC, PRCA 446 GRIVAFFSF AML, BRCA, CRC, HCC, HNSCC, MEL, NHL, NSCLC, OSCAR, PACA, PRCA, SCLC, UBC, UEC 447 MQVLVSRI GC, NSCLC, PACA, PRCA, RCC, SCLC 448 LSQKGYSW NHL, NSCLC, UBC 451 DYLNEWGSRF NSCLC, OSCAR, UEC 454 AQTDPTTGY GBM, GC, NSCLC 455 AAAANAQVY BRCA, UEC 456 IPLERPLGEVY BRCA, UEC 457 NAAAAANAQVY BRCA, NSCLC, UEC 458 TDTLIHLM UEC 459 KVAGERYVY BRCA, CCC, CRC, GBM, HNSCC, MEL, NSCLC, OSCAR, PACA, PRCA, SCLC, UBC 460 RLSSATANALY GBC 461 AQRMTTQLL CRC, MEL, NSCLC, RCC 462 QRMTTQLLL NSCLC, RCC, UEC 466 DLIESGQLRER UEC 467 MQMQERDTL GEJC, HNSCC, NHL, NSCLC, OSCAR 471 AQRLDPVYF CCC, CRC, GBC, GEJC, NSCLC, OSCAR, PACA, SCLC, UBC 472 MRLLVAPL SCLC, UEC 474 AADGGLRASVTL BRCA, NSCLC, OSCAR 477 RIQQQTNTY GBM, SCLC 479 TEGSHFVEA BRCA, SCLC, UEC 480 GRADIMIDF BRCA, CRC, HNSCC, MEL, NSCLC, OSCAR, SCLC, UEC 481 GRWEKTDLTY BRCA, GBC, HNSCC, MEL, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 482 GRWEKTDLTYR HNSCC, NSCLC, OSCAR, PACA, SCLC, UEC 484 AWLRSAAA CCC 485 VRFPVHAAL MEL, NSCLC, OSCAR 486 DRFFWLKV NSCLC, SCLC 487 GMADILVVF NSCLC 488 RSFSLGVPR AML, CLL, GC, HCC, HNSCC, NHL, NSCLC, PRCA, SCLC, UEC 490 AEVQKLLGP HNSCC, NSCLC, OSCAR, UEC 491 EAYSSTSSW GBC, UEC 493 DTNLEPVTR UEC 495 EVPSGATTEVSR UEC 496 EVPTGTTAEVSR UEC 498 EVYPELGTQGR UEC 503 TVFDKAFTAA NSCLC 507 TSIFSGQSL UEC 508 TVAKTTTTF UEC 509 GRGPGGVSW NSCLC 518 TSDFPTITV PACA 520 THSAMTHGF NHL 527 QSTPYVNSV UEC 528 TRTGLFLRF HNSCC, NSCLC, UEC 533 GQHLHLETF AML, CCC, GBC, GC, HCC, MEL, NHL, NSCLC, OSCAR, RCC, SCLC, UBC, UEC 537 IRRLKELKDQ NSCLC 539 IPIPSTGSVEM CCC, GC, HNSCC, NSCLC, OSCAR, PRCA, SCLC, UBC, UEC 540 AGIPAVALW HCC, NSCLC, OSCAR 541 RLSPAPLKL GBM, NSCLC 544 LRNPSIQKL GBM 545 RVGPPLLI BRCA, CRC, NSCLC, OSCAR, UEC 546 GRAFFAAAF CRC, GBM, HNSCC, MEL, NSCLC, OSCAR, PACA, SCLC, UBC, UEC 547 EVNKPGVYTR HCC, UEC 549 ARSKLQQGL MEL 550 RRFKEPWFL BRCA, HCC, MEL, NSCLC, PRCA, SCLC, UBC, UEC 563 PNFSGNWKIIRSENFEEL NSCLC 589 APDAKSFVLNLGKDSNNL NSCLC 590 RVRGEVAPDAKSFVLNLG NSCLC 591 VRGEVAPDAKSFVLNL NSCLC, RCC 592 VRGEVAPDAKSFVLNLG NSCLC, RCC 593 GEVAPDAKSFVLNLG NSCLC, RCC 594 VRGEVAPDAKSFVLN NSCLC, RCC 598 AESLFREALSNKVDEL NSCLC 599 AESLFREALSNKVDE NSCLC 607 LTVAEVQKLLGPHVEGLKAEE NSCLC 608 LTVAEVQKLLGPHVEGLKAE NSCLC 609 LTVAEVQKLLGPHVEGLKA NSCLC 610 LTVAEVQKLLGPHVEGLK NSCLC 611 LTVAEVQKLLGPHVEGL NSCLC 612 TVAEVQKLLGPHVEGLK NSCLC 613 LTVAEVQKLLGPHVEG NSCLC 614 TVAEVQKLLGPHVEGL NSCLC 615 VAEVQKLLGPHVEGLK NSCLC 616 TVAEVQKLLGPHVEG NSCLC 617 VAEVQKLLGPHVEGL NSCLC 618 VAEVQKLLGPHVEG NSCLC 619 VAEVQKLLGPHVE NSCLC 620 EVQKLLGPHVEG NSCLC 625 DALRGLLPVLGQPIIRSIPQG NSCLC 628 DALRGLLPVLGQPIIRSIPQ NSCLC 629 GLLPVLGQPIIRSIPQGIVA NSCLC 630 ALRGLLPVLGQPIIRSIPQ NSCLC 633 LRGLLPVLGQPIIRSIPQ NSCLC 634 DALRGLLPVLGQPIIRS NSCLC 635 ALRGLLPVLGQPIIRS NSCLC 637 ALRGLLPVLGQPIIR NSCLC 638 LRGLLPVLGQPIIRS NSCLC 639 ALRGLLPVLGQPII NSCLC 646 GLLPVLGQPIIRSIPQGIVAAWRQ NSCLC 648 GLLPVLGQPIIRSIPQGIVAA NSCLC 651 LPVLGQPIIRSIPQGIVAA NSCLC 653 LPVLGQPIIRSIPQGIVA NSCLC 654 PVLGQPIIRSIPQGIVA GC, NSCLC 656 VLGQPIIRSIPQGIVA NSCLC 661 LRGLLPVLGQPIIRSIPQG NSCLC 666 LPLTVAEVQKLLGPHVEG NSCLC 668 AVLPLTVAEVQK BRCA, CRC, GBC, GC, NSCLC, PACA, UEC 677 IWAVRPQDLDTCDPR NSCLC 680 GVRGSLLSEADVRALGGLA NSCLC 682 GVRGSLLSEADVRALGGL NSCLC 686 VRGSLLSEADVRALGGL NSCLC 694 GSLLSEADVRALGG NSCLC 695 RGSLLSEADVRALG NSCLC 697 GSLLSEADVRALG NSCLC 717 IPQGIVAAWRQRSSRDPS GC 730 LPGRFVAESAEVL NSCLC

Example 2

(23) Expression Profiling of Genes Encoding the Peptides of the Invention

(24) Over-presentation or specific presentation of a peptide on tumor cells compared to normal cells is sufficient for its usefulness in immunotherapy, and some peptides are tumor-specific despite their source protein occurring also in normal tissues. Still, mRNA expression profiling adds an additional level of safety in selection of peptide targets for immunotherapies. Especially for therapeutic options with high safety risks, such as affinity-matured TORs, the ideal target peptide will be derived from a protein that is unique to the tumor and not found on normal tissues.

(25) RNA Sources and Preparation

(26) Surgically removed tissue specimens were provided as indicated above (see Example 1) after written informed consent had been obtained from each patient. Tumor tissue specimens were snap-frozen immediately after surgery and later homogenized with mortar and pestle under liquid nitrogen. Total RNA was prepared from these samples using TRI Reagent (Ambion, Darmstadt, Germany) followed by a cleanup with RNeasy (QIAGEN, Hilden, Germany); both methods were performed according to the manufacturer's protocol.

(27) Total RNA from healthy human tissues for RNASeq experiments was obtained from: Asterand (Detroit, Mich., USA & Royston, Herts, UK); Bio-Options Inc. (Brea, Calif., USA); Geneticist Inc. (Glendale, Calif., USA); ProteoGenex Inc. (Culver City, Calif., USA); Tissue Solutions Ltd (Glasgow, UK).

(28) Total RNA from tumor tissues for RNASeq experiments was obtained from: Asterand (Detroit, Mich., USA & Royston, Herts, UK); BioCat GmbH (Heidelberg, Germany); BioServe (Beltsville, Md., USA); Geneticist Inc. (Glendale, Calif., USA); Istituto Nazionale Tumori “Pascale” (Naples, Italy); ProteoGenex Inc. (Culver City, Calif., USA); University Hospital Heidelberg (Heidelberg, Germany).

(29) Quality and quantity of all RNA samples were assessed on an Agilent 2100 Bioanalyzer (Agilent, Waldbronn, Germany) using the RNA 6000 Pico LabChip Kit (Agilent).

(30) RNAseq Experiments

(31) Gene expression analysis of—tumor and normal tissue RNA samples was performed by next generation sequencing (RNAseq) by CeGaT (Tübingen, Germany). Briefly, sequencing libraries are prepared using the Illumina HiSeq v4 reagent kit according to the provider's protocol (Illumina Inc., San Diego, Calif., USA), which includes RNA fragmentation, cDNA conversion and addition of sequencing adaptors. Libraries derived from multiple samples are mixed equimolar and sequenced on the Illumina HiSeq 2500 sequencer according to the manufacturer's instructions, generating 50 bp single end reads. Processed reads are mapped to the human genome (GRCh38) using the STAR software. Expression data are provided on transcript level as RPKM (Reads Per Kilobase per Million mapped reads, generated by the software Cufflinks) and on exon level (total reads, generated by the software Bedtools), based on annotations of the ensembl sequence database (Ensembl77). Exon reads are normalized for exon length and alignment size to obtain RPKM values.

(32) Exemplary expression profiles of source genes of the present invention that are highly over-expressed or exclusively expressed in ovarian cancer are shown in FIGS. 1A through 1V. Expression scores for further exemplary genes are shown in Table 10.

(33) TABLE-US-00011 TABLE 10 Expression scores. The table lists peptides from genes that are very highly over-expressed in OC tumors compared to a panel of normal tissues (+++), highly over-expressed in OC tumors compared to a panel of normal tissues (++) or over-expressed in OC tumors compared to a panel of normal tissues (+). The baseline for this score was calculated from measurements of the following relevant normal tissues adipose tissue, adrenal gland, bile duct, blood cells, blood vessels, bone marrow, brain, cartilage, esophagus, eye, gallbladder, heart, head&neck, kidney, large intestine, liver, lung, lymph node, nerve, parathyroid, pancreas, pituitary, skeletal muscle, skin, small intestine, spleen, stomach, thyroid gland, trachea, urinary bladder. In case expression data for several samples of the same tissue type were available, the arithmetic mean of all respective samples was used for the calculation. Seq ID No Sequence Gene Expression 1 MIPTFTALL ++ 5 RLLDFINVL +++ 6 SLGKHTVAL +++ 10 RYSDSVGRVSF + 11 SYSDLHYGF ++ 12 KYEKIFEML +++ 13 VYTFLSSTL +++ 14 FYFPTPTVL ++ 16 IYSPQFSRL +++ 17 RFTTMLSTF +++ 18 KYPVHIYRL + 20 RMASPVNVK ++ 21 AVRKPIVLK + 22 SLKERNPLK ++ 23 GMMKGGIRK +++ 25 GTSPPSVEK ++ 26 RISEYLLEK +++ 27 VLYGPAGLGK +++ 28 KTYETNLEIKK +++ 29 QQFLTALFY +++ 30 ALEVAHRLK + 31 LLDEGAMLLY +++ 32 SPNKGTLSV + 33 SPTFHLTL + 34 LPRGPLASLL ++ 35 FPDNQRPAL ++ 36 APAAWLRSA +++ 37 RPLFQKSSM +++ 38 SPHPVTALLTL ++ 39 RPAPFEVVF ++ 40 KPGTSYRVTL +++ 42 TLKVTSAL + 43 ALKARTVTF + 47 MPNLRSVDL +++ 51 SLRLKNVQL +++ 52 AEFLLRIFL + 53 MEHPGKLLF +++ 54 AEITITTQTGY ++ 55 HETETRTTW ++ 56 SEPDTTASW ++ 57 QESDLRLFL +++ 58 GEMEQKQL +++ 59 SENVTMKVV +++ 60 GLLSLTSTLYL + 61 YMVHIQVTL ++ 62 KVLGVNVML ++ 63 MMEEMIFNL ++ 64 FLDPDRHFL ++ 66 GLLQELSSI +++ 67 SLLLPSIFL +++ 69 TTYEGSITV ++ 70 VLQGLLRSL +++ 71 YLEDTDRNL + 72 YLTDLQVSL + 73 FLIEELLFA +++ 74 SQSPSVSQL +++ 75 KVVSVLYNV +++ 76 KYVAELSLL +++ 77 RYGPVFTV +++ 78 SFAPRSAVF ++ 82 SYFRGFTLI +++ 83 GTYAHTVNR +++ 84 KLQPAQTAAK +++ 87 AVAPPTPASK ++ 88 VVHAVFALK + 89 RVAELLLLH +++ 90 KVAGERYVYK ++ 91 RSLRYYYEK ++ 92 SVFPIENIY ++ 96 TAFGGFLKY +++ 97 TMLDVEGLFY ++ 98 LLQPPPLLAR +++ 100 RLFTSPIMTK ++ 101 RVFTSSIKTK ++ 102 SVLTSSLVK ++ 103 TSRSVDEAY ++ 104 VLADSVTTK ++ 107 RLQEWKALK +++ 108 VLYPVPLESY +++ 110 SAAPPSYFR +++ 111 TLPQFRELGY ++ 112 TVTGAEQIQY ++ 113 QLDSNRLTY ++ 114 VMEQSAGIMY +++ 115 FVDNQYWRY +++ 116 VLLDEGAMLLY +++ 117 APRLLLLAVL ++ 118 SPASRSISL ++ 119 APLPRPGAVL +++ 120 RPAMNYDKL ++ 121 VPNQSSESL +++ 122 YPGFPQSQY +++ 123 KPSESIYSAL +++ 124 LPSDSHFKITF +++ 125 VPVYILLDEM ++ 126 KPGPEDKL ++ 128 YPRTITPGM + 129 APRPASSL ++ 130 FPRLVGPDF + 131 APTEDLKAL ++ 132 IPGPAQSTI ++ 133 MPNLPSTTSL ++ 135 RVRSTISSL ++ 136 SPFSAEEANSL ++ 137 SPGATSRGTL ++ 138 SPMATTSTL ++ 139 SPQSMSNTL ++ 140 SPRTEASSAVL ++ 141 SPMTSLLTSGL ++ 142 TPGLRETSI ++ 143 SPAMTSTSF ++ 144 SPSPVSSTL ++ 145 SPSSPMSTF ++ 147 APRWFPQPTVV +++ 151 HLLLKVLAF +++ 152 MGSARVAEL +++ 154 MLRKIAVAA ++ 155 NKKMMKRLM +++ 156 HVKEKFLL ++ 157 EAMKRLSYI + 159 VLKHKLDEL ++ 160 YPKARLAF ++ 161 ALKTTTTAL ++ 162 QAKTHSTL ++ 163 QGLLRPVF +++ 164 SIKTKSAEM ++ 165 SPRFKTGL ++ 166 TPKLRETSI ++ 167 TSHERLTTL ++ 168 TSHERLTTY ++ 169 TSMPRSSAM ++ 170 YLLEKSRVI +++ 171 FAFRKEAL +++ 172 KLKERNREL +++ 173 AEAQVGDERDY + 174 AEATARLNVF + 175 AEIEPKADG + 176 AEIEPKADGSW + 177 TEVGTMNLF ++ 181 GEGPKTSW + 183 YEKGIMQKV ++ 184 AELEALTDLW ++ 185 AERQPGAASL ++ 186 REGPEEPGL ++ 187 GEAQTRIAW ++ 189 KEFLFNMY ++ 190 YEVARILNL ++ 193 LEAQQEAL ++ 194 KEVDPTSHSY +++ 195 AEDKRHYSV + 196 REMPGGPVW +++ 197 AEVLLPRLV ++ 198 QEAARAAL ++ 199 REIDESLIFY ++ 200 AESIPTVSF ++ 201 AETILTFHAF ++ 202 HESEATASW ++ 203 IEHSTQAQDTL ++ 204 RETSTSEETSL ++ 205 SEITRIEM ++ 206 SESVTSRTSY +++ 207 TEARATSDSW ++ 208 TEVSRTEAI ++ 209 TEVSRTEL ++ 210 VEAADIFQNF ++ 211 EEKVFPSPLW +++ 212 MEQKQLQKRF +++ 214 VEQTRAGSLL ++ 216 IMFDDAIERA +++ 217 VSSSLTLKV + 218 TIASQRLTPL ++ 219 PLPRPGAVL +++ 220 RMTTQLLLL ++ 225 SVFAHPRKL ++ 226 QVDPKKRISM ++ 227 YTFRYPLSL ++ 229 ISVPAKTSL ++ 230 SAFREGTSL ++ 231 SVTESTHHL ++ 232 TISSLTHEL ++ 233 GSDTSSKSL ++ 234 GVATRVDAI +++ 235 SAIETSAVL ++ 236 SAIPFSMTL ++ 237 SAMGTISIM ++ 238 PLLVLFTI +++ 239 FAVPTGISM ++ 240 FSTDTSIVL ++ 241 RQPNILVHL ++ 242 STIPALHEI ++ 243 YASEGVKQV ++ 244 DTDSSVHVQV ++ 246 RYLAVVHAVF + 247 ARPPWMWVL +++ 248 SVIQHLGY ++ 249 VYTPTLGTL ++ 250 HFPEKTTHSF ++ 252 LYQPRASEM +++ 254 IIQHLTEQF +++ 255 VFVSFSSLF +++ 256 RTEEVLLTFK ++ 257 VTADHSHVF +++ 258 GAYAHTVNR +++ 259 KTLELRVAY + 260 GTNTVILEY ++ 261 HTFGLFYQR ++ 262 RSRLNPLVQR ++ 263 SSSSATISK ++ 266 ISYSGQFLVK +++ 267 VTDLISPRK +++ 268 GLLGLSLRY +++ 269 RLKGDAWVYK ++ 270 AVFNPRFYRTY +++ 272 RQPERTILRPR ++ 273 RVNAIPFTY ++ 274 KTFPASTVF ++ 275 STTFPTLTK ++ 276 VSKTTGMEF ++ 277 TTALKTTSR ++ 278 NLSSITHER ++ 279 SVSSETTKIKR ++ 280 SVSGVKTTF ++ 281 RAKELEATF +++ 282 CLTRTGLFLRF +++ 285 GTVNPTVGK ++ 286 TVAPPQGVVK + 287 RRIHTGEKPYK ++ 288 SPVTSVHGGTY + 289 RWEKTDLTY ++ 290 DMDEEIEAEY +++ 291 ETIRSVGYY ++ 292 NVTMKVVSVLY +++ 293 VPDSGATATAY +++ 294 YPLRGSSIF +++ 295 YPLRGSSIFGL +++ 296 YPLRGSSI +++ 297 TVREASGLL + 298 YPTEHVQF + 299 HPGSSALHY ++ 301 SPRRSPRISF + 302 RVEEVRALL +++ 303 LPMWKVTAF +++ 304 LPRPGAVL +++ 305 TPWAESSTKF ++ 306 APVIFSHSA ++ 307 LPYGPGSEAAAF +++ 308 YPEGAAYEF +++ 309 FPQSQYPQY +++ 310 RPNPITIIL +++ 311 RPLFYVVSL +++ 312 LPYFREFSM +++ 313 KVKSDRSVF +++ 315 SPRENFPDTL +++ 316 EPKTATVL ++ 320 FPMSPVTSV + 321 SPMDTFLLI + 322 SPDPSKHLL + 323 RPMPNLRSV +++ 324 VPYRVVGL +++ 326 VPSEIDAAF ++ 327 SPLPVTSLI ++ 328 EPVTSSLPNF ++ 329 FPAMTESGGMIL ++ 330 FPFVTGSTEM ++ 331 FPHPEMTTSM ++ 332 FPHSEMTTL ++ 333 FPHSEMTTVM ++ 334 FPYSEVTTL ++ 335 HPDPVGPGL +++ 336 HPKTESATPAAY ++ 337 HPVETSSAL ++ 338 HVTKTQATF ++ 339 LPAGTTGSLVF ++ 340 LPEISTRTM ++ 341 LPLDTSTTL ++ 342 LPLGTSMTF ++ 343 LPSVSGVKTTF ++ 344 LPTQTTSSL ++ 345 LPTSESLVSF ++ 346 LPWDTSTTLF ++ 347 MPLTTGSQGM ++ 348 MPNSAIPFSM ++ 349 MPSLSEAMTSF ++ 350 NPSSTTTEF ++ 351 NVLTSTPAF ++ 352 SPAETSTNM ++ 353 SPAMTTPSL ++ 354 SPLPVTSLL ++ 355 SPLVTSHIM ++ 356 SPNEFYFTV ++ 357 SPSPVPTTL ++ 358 SPSPVTSTL ++ 359 SPSTIKLTM ++ 360 SPSVSSNTY ++ 361 SPTHVTQSL ++ 362 SPVPVTSLF ++ 363 TAKTPDATF ++ 364 TPLATTQRF ++ 365 TPLATTQRFTY ++ 366 TPLTTTGSAEM ++ 367 TPSVVTEGF ++ 368 VPTPVFPTM ++ 369 FPHSEMTTV ++ 370 PGGTRQSL ++ 372 IPRNPPPTLL +++ 373 RPRALRDLRIL +++ 374 NPIGDTGVKF +++ 375 AAASPLLLL +++ 376 RPRSPAGQVA +++ 377 RPRSPAGQVAAA +++ 378 RPRSPAGQVAA +++ 379 GPFPLVYVL +++ 380 IPTYGRTF +++ 381 LPEQTPLAF +++ 382 SPMHDRWTF +++ 383 TPTKETVSL +++ 384 YPGLRGSPM +++ 387 APLKLSRTPA +++ 388 SPAPLKLSRTPA +++ 389 SPGAQRTFFQL ++ 395 VLLPRLVSC ++ 396 REASGLLSL + 397 REGDTVQLL + 399 RELLHLVTL + 400 GEIEIHLL + 403 EEAQWVRKY ++ 404 NEAIMHQY ++ 405 NEIWTHSY ++ 411 LELPPILVY + 412 QEILTQVKQ +++ 413 IEALSGKIEL +++ 416 SEEETRVVF ++ 417 AEHFSMIRA +++ 418 FEDAQGHIW ++ 419 HEFGHVLGL ++ 420 FESHSTVSA ++ 421 GEPATTVSL ++ 422 SETTFSLIF ++ 423 SEVPTGTTA ++ 424 TEFPLFSAA ++ 425 SEVPLPMAI ++ 426 PEKTTHSF ++ 427 HESSSHHDL + 428 LDLGLNHI ++ 429 REKFIASVI +++ 430 DEKILYPEF +++ 432 EEQYIAQF +++ 433 SDSQVRAF +++ 435 REEFVSIDHL +++ 436 REPGDIFSEL +++ 437 TEAVVTNEL +

Example 3

(34) In Vitro Immunogenicity for MHC Class I Presented Peptides

(35) In order to obtain information regarding the immunogenicity of the TUMAPs of the present invention, the inventors performed investigations using an in vitro T-cell priming assay based on repeated stimulations of CD8+ T cells with artificial antigen presenting cells (aAPCs) loaded with peptide/MHC complexes and anti-CD28 antibody. This way the inventors could show immunogenicity for HLA-A*0201, HLA-A*24:02, HLA-A*01:01, HLA-A*03:01, HLA-B*07:02 and HLA-B*44:02 restricted TUMAPs of the invention, demonstrating that these peptides are T-cell epitopes against which CD8+ precursor T cells exist in humans (Table 11).

(36) In Vitro Priming of CD8+ T Cells

(37) In order to perform in vitro stimulations by artificial antigen presenting cells loaded with peptide-MHC complex (pMHC) and anti-CD28 antibody, the inventors first isolated CD8+ T cells from fresh HLA-A*02, HLA-A*24, HLA-A*01, HLA-A*03, HLA-B*07 or HLA-B*44 leukapheresis products via positive selection using CD8 microbeads (Miltenyi Biotec, Bergisch-Gladbach, Germany) of healthy donors obtained from the University clinics Mannheim, Germany, after informed consent.

(38) PBMCs and isolated CD8+ lymphocytes were incubated in T-cell medium (TCM) until use consisting of RPMI-Glutamax (Invitrogen, Karlsruhe, Germany) supplemented with 10% heat inactivated human AB serum (PAN-Biotech, Aidenbach, Germany), 100 U/ml Penicillin/100 μg/ml Streptomycin (Cambrex, Cologne, Germany), 1 mM sodium pyruvate (CC Pro, Oberdorla, Germany), 20 μg/ml Gentamycin (Cambrex). 2.5 ng/ml IL-7 (PromoCell, Heidelberg, Germany) and 10 U/ml IL-2 (Novartis Pharma, Nürnberg, Germany) were also added to the TCM at this step.

(39) Generation of pMHC/anti-CD28 coated beads, T-cell stimulations and readout was performed in a highly defined in vitro system using four different pMHC molecules per stimulation condition and 8 different pMHC molecules per readout condition.

(40) The purified co-stimulatory mouse IgG2a anti human CD28 Ab 9.3 (Jung et al., 1987) was chemically biotinylated using sulfo-N-hydroxysuccinimidobiotin as recommended by the manufacturer (Perbio, Bonn, Germany). Beads used were 5.6 μm diameter streptavidin coated polystyrene particles (Bangs Laboratories, Illinois, USA).

(41) pMHC used for positive and negative control stimulations were A*0201/MLA-001 (peptide ELAGIGILTV (SEQ ID NO. 775) from modified Melan-A/MART-1) and A*0201/DDX5-001 (YLLPAIVHI from DDX5, SEQ ID NO. 776), respectively.

(42) 800.000 beads/200 μl were coated in 96-well plates in the presence of 4×12.5 ng different biotin-pMHC, washed and 600 ng biotin anti-CD28 were added subsequently in a volume of 200 μl. Stimulations were initiated in 96-well plates by co-incubating 1×10.sup.6 CD8+ T cells with 2×10.sup.5 washed coated beads in 200 μl TCM supplemented with 5 ng/ml IL-12 (PromoCell) for 3 days at 37° C. Half of the medium was then exchanged by fresh TCM supplemented with 80 U/ml IL-2 and incubating was continued for 4 days at 37° C. This stimulation cycle was performed for a total of three times. For the pMHC multimer readout using 8 different pMHC molecules per condition, a two-dimensional combinatorial coding approach was used as previously described (Andersen et al., 2012) with minor modifications encompassing coupling to 5 different fluorochromes. Finally, multimeric analyses were performed by staining the cells with Live/dead near IR dye (Invitrogen, Karlsruhe, Germany), CD8-FITC antibody clone SK1 (BD, Heidelberg, Germany) and fluorescent pMHC multimers. For analysis, a BD LSRII SORP cytometer equipped with appropriate lasers and filters was used. Peptide specific cells were calculated as percentage of total CD8+ cells. Evaluation of multimeric analysis was done using the FlowJo software (Tree Star, Oreg., USA). In vitro priming of specific multimer+ CD8+ lymphocytes was detected by comparing to negative control stimulations. Immunogenicity for a given antigen was detected if at least one evaluable in vitro stimulated well of one healthy donor was found to contain a specific CD8+ T-cell line after in vitro stimulation (i.e. this well contained at least 1% of specific multimer+ among CD8+ T-cells and the percentage of specific multimer+ cells was at least 10× the median of the negative control stimulations).

(43) In Vitro Immunogenicity for Ovarian Cancer Peptides

(44) For tested HLA class I peptides, in vitro immunogenicity could be demonstrated by generation of peptide specific T-cell lines. Exemplary flow cytometry results after TUMAP-specific multimer staining for 14 peptides of the invention are shown in FIGS. 2 through 9B together with corresponding negative controls. Results for 118 peptides from the invention are summarized in Table 11a and Table 11b.

(45) TABLE-US-00012 TABLE 11a in vitro immunogenicity of HLA class I peptides of the invention. Exemplary results of in vitro immunogenicity experiments conducted by the applicant for the peptides of the invention. <20% = +; 20%-49% = ++; 50%-69% = +++; >= 70% = ++++ Seq ID Sequence Wells positive [%] 773 ALYGKLLKL +++ 774 VYVDDIYVI +++

(46) TABLE-US-00013 TABLE 11b in vitro immunogenicity of HLA class I peptides of the invention. Exemplary results of in vitro immunogenicity experiments conducted by the applicant for the peptides of the invention. <20% = +; 20%-49% = ++; 50%-69% = +++; >= 70% = ++++ Seq ID No Sequence Wells positive [%] HLA 2 TLLKALLEI ++ A*02 3 ALIYNLVGI ++ A*02 4 ALFKAWAL ++++ A*02 5 RLLDFINVL ++ A*02 7 ALQAFEFRV ++++ A*02 60 GLLSLTSTLYL + A*02 62 KVLGVNVML ++ A*02 64 FLDPDRHFL +++ A*02 66 GLLQELSSI + A*02 67 SLLLPSIFL +++ A*02 71 YLEDTDRNL + A*02 73 FLIEELLFA +++ A*02 75 KVVSVLYNV +++ A*02 11 SYSDLHYGF +++ A*24 12 KYEKIFEML + A*24 13 VYTFLSSTL + A*24 16 IYSPQFSRL + A*24 18 KYPVHIYRL + A*24 79 SYNEHWNYL + A*24 80 TAYMVSVAAF + A*24 82 SYFRGFTLI + A*24 113 QLDSNRLTY + A*01 115 FVDNQYWRY + A*01 20 RMASPVNVK + A*03 21 AVRKPIVLK + A*03 22 SLKERNPLK + A*03 23 GMMKGGIRK ++ A*03 24 SMYYPLQLK + A*03 25 GTSPPSVEK +++ A*03 26 RISEYLLEK + A*03 27 VLYGPAGLGK + A*03 28 KTYETNLEIKK + A*03 30 ALEVAHRLK ++ A*03 83 GTYAHTVNR + A*03 84 KLQPAQTAAK + A*03 85 VLLGSLFSRK + A*03 86 VVLLGSLFSRK + A*03 87 AVAPPTPASK + A*03 90 KVAGERYVYK +++ A*03 91 RSLRYYYEK ++ A*03 94 ATFERVLLR + A*03 95 QSMYYPLQLK + A*03 99 KVVDRWNEK ++ A*03 100 RLFTSPIMTK + A*03 102 SVLTSSLVK + A*03 106 AAFVPLLLK +++ A*03 109 KTFTIKRFLAK + A*03 110 SAAPPSYFR ++ A*03 32 SPNKGTLSV + B*07 33 SPTFHLTL ++++ B*07 34 LPRGPLASLL + B*07 35 FPDNQRPAL + B*07 36 APAAWLRSA +++ B*07 37 RPLFQKSSM + B*07 38 SPHPVTALLTL + B*07 39 RPAPFEVVF +++ B*07 40 KPGTSYRVTL ++++ B*07 41 RVRSRISNL + B*07 118 SPASRSISL + B*07 119 APLPRPGAVL ++ B*07 120 RPAMNYDKL + B*07 121 VPNQSSESL + B*07 123 KPSESIYSAL ++ B*07 124 LPSDSHFKITF ++ B*07 128 YPRTITPGM + B*07 129 APRPASSL + B*07 130 FPRLVGPDF +++ B*07 131 APTEDLKAL ++ B*07 133 MPNLPSTTSL ++++ B*07 134 RPIVPGPLL ++ B*07 139 SPQSMSNTL + B*07 140 SPRTEASSAVL + B*07 141 SPMTSLLTSGL ++ B*07 146 IPRPEVQAL +++ B*07 147 APRWFPQPTVV ++ B*07 148 KPYGGSGPL + B*07 149 GPREALSRL ++ B*07 52 AEFLLRIFL + B*44 53 MEHPGKLLF + B*44 55 HETETRTTW +++ B*44 57 QESDLRLFL + B*44 58 GEMEQKQL ++++ B*44 59 SENVTMKVV ++ B*44 174 AEATARLNVF + B*44 175 AEIEPKADG ++++ B*44 177 TEVGTMNLF ++ B*44 178 NELFRDGVNW + B*44 179 REAGDEFEL + B*44 180 REAGDEFELRY ++++ B*44 181 GEGPKTSW + B*44 182 KEATEAQSL + B*44 183 YEKGIMQKV ++++ B*44 184 AELEALTDLW + B*44 186 REGPEEPGL + B*44 187 GEAQTRIAW ++ B*44 188 AEFAKKQPVWW ++ B*44 189 KEFLFNMY ++++ B*44 190 YEVARILNL ++++ B*44 191 EEDAALFKAW +++ B*44 192 YEFKFPNRL + B*44 195 AEDKRHYSV +++ B*44 197 AEVLLPRLV ++ B*44 198 QEAARAAL ++ B*44 199 REIDESLIFY + B*44 200 AESIPTVSF +++ B*44 201 AETILTFHAF +++ B*44 202 HESEATASW ++ B*44 203 IEHSTQAQDTL ++++ B*44 205 SEITRIEM ++++ B*44 207 TEARATSDSW + B*44 208 TEVSRTEAI + B*44 209 TEVSRTEL ++++ B*44 210 VEAADIFQNF + B*44 211 EEKVFPSPLW +++ B*44 212 MEQKQLQKRF ++ B*44 213 KESIPRWYY + B*44

Example 4

(47) Synthesis of Peptides

(48) All peptides were synthesized using standard and well-established solid phase peptide synthesis using the Fmoc-strategy. Identity and purity of each individual peptide have been determined by mass spectrometry and analytical RP-HPLC. The peptides were obtained as white to off-white lyophilizes (trifluoro acetate salt) in purities of >50%. All TUMAPs are preferably administered as trifluoro-acetate salts or acetate salts, other salt-forms are also possible.

Example 5

(49) MHC Binding Assays

(50) Candidate peptides for T cell based therapies according to the present invention were further tested for their MHC binding capacity (affinity). The individual peptide-MHC complexes were produced by UV-ligand exchange, where a UV-sensitive peptide is cleaved upon UV-irradiation, and exchanged with the peptide of interest as analyzed. Only peptide candidates that can effectively bind and stabilize the peptide-receptive MHC molecules prevent dissociation of the MHC complexes. To determine the yield of the exchange reaction, an ELISA was performed based on the detection of the light chain (β2m) of stabilized MHC complexes. The assay was performed as generally described in Rodenko et al. (Rodenko et al., 2006).

(51) 96 well MAXISorp plates (NUNC) were coated over night with 2 ug/ml streptavidin in PBS at room temperature, washed 4× and blocked for 1 h at 37° C. in 2% BSA containing blocking buffer. Refolded HLA-A*02:01/MLA-001 monomers served as standards, covering the range of 15-500 ng/ml. Peptide-MHC monomers of the UV-exchange reaction were diluted 100-fold in blocking buffer. Samples were incubated for 1 h at 37° C., washed four times, incubated with 2 ug/ml HRP conjugated anti-β2m for 1 h at 37° C., washed again and detected with TMB solution that is stopped with NH.sub.2SO.sub.4. Absorption was measured at 450 nm. Candidate peptides that show a high exchange yield (preferably higher than 50%, most preferred higher than 75%) are generally preferred for a generation and production of antibodies or fragments thereof, and/or T cell receptors or fragments thereof, as they show sufficient avidity to the MHC molecules and prevent dissociation of the MHC complexes.

(52) TABLE-US-00014 TABLE 12 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-A*02:01 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Seq ID No Sequence Peptide exchange 1 MIPTFTALL +++ 2 TLLKALLEI ++++ 3 ALIYNLVGI ++++ 4 ALFKAWAL ++++ 5 RLLDFINVL ++++ 6 SLGKHTVAL +++ 7 ALQAFEFRV ++++ 8 YLVTKVVAV ++++ 9 VLLAGFKPPL + 60 GLLSLTSTLYL ++++ 61 YMVHIQVTL ++++ 62 KVLGVNVML ++++ 63 MMEEMIFNL ++++ 64 FLDPDRHFL ++++ 66 GLLQELSSI ++++ 67 SLLLPSIFL ++++ 68 KLFDTQQFL ++++ 69 TTYEGSITV ++++ 70 VLQGLLRSL ++++ 71 YLEDTDRNL ++++ 72 YLTDLQVSL ++++ 73 FLIEELLFA ++++ 75 KVVSVLYNV ++++ 216 IMFDDAIERA ++++ 217 VSSSLTLKV + 219 PLPRPGAVL + 220 RMTTQLLLL +++ 221 SLLDLYQL ++ 222 ALMRLIGCPL ++++ 223 FAHHGRSL + 224 SLPRFQVTL ++++ 225 SVFAHPRKL +++ 227 YTFRYPLSL +++ 228 RLWDWVPLA ++++ 229 ISVPAKTSL + 231 SVTESTHHL +++ 232 TISSLTHEL ++++ 234 GVATRVDAI ++ 236 SAIPFSMTL +++ 241 RQPNILVHL ++ 242 STIPALHEI +++ 243 YASEGVKQV +++ 244 DTDSSVHVQV +

(53) TABLE-US-00015 TABLE 13 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-A*24:02 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Seq ID No Sequence Peptide exchange 10 RYSDSVGRVSF ++++ 11 SYSDLHYGF ++++ 12 KYEKIFEML ++++ 13 VYTFLSSTL ++++ 14 FYFPTPTVL ++++ 15 VYHDDKQPTF ++++ 16 IYSPQFSRL ++++ 17 RFTTMLSTF ++++ 18 KYPVHIYRL ++++ 19 KYVKVFHQF ++++ 76 KYVAELSLL ++++ 77 RYGPVFTV ++++ 78 SFAPRSAVF ++++ 79 SYNEHWNYL ++++ 80 TAYMVSVAAF +++ 81 VYNHTTRPL ++++ 82 SYFRGFTLI ++++ 246 RYLAVVHAVF ++++ 249 VYTPTLGTL ++++ 252 LYQPRASEM +++ 255 VFVSFSSLF +++

(54) TABLE-US-00016 TABLE 14 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-A*01:01 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Seq ID No Sequence Peptide exchange 31 LLDEGAMLLY ++++ 112 TVTGAEQIQY ++ 113 QLDSNRLTY +++ 114 VMEQSAGIMY ++ 115 FVDNQYWRY +++ 116 VLLDEGAMLLY ++ 288 SPVTSVHGGTY ++ 289 RWEKTDLTY ++ 290 DMDEEIEAEY ++ 291 ETIRSVGYY +++ 292 NVTMKVVSVLY +++

(55) TABLE-US-00017 TABLE 15 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-A*03:01 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Seq ID No Sequence Peptide exchange 20 RMASPVNVK ++++ 21 AVRKPIVLK +++ 22 SLKERNPLK ++ 23 GMMKGGIRK +++ 24 SMYYPLQLK +++ 25 GTSPPSVEK ++ 26 RISEYLLEK ++ 27 VLYGPAGLGK +++ 28 KTYETNLEIKK +++ 30 ALEVAHRLK ++ 83 GTYAHTVNR +++ 84 KLQPAQTAAK ++ 85 VLLGSLFSRK ++ 86 VVLLGSLFSRK ++ 87 AVAPPTPASK ++ 88 VVHAVFALK +++ 89 RVAELLLLH ++ 90 KVAGERYVYK +++ 91 RSLRYYYEK ++ 93 KILEEHTNK ++ 94 ATFERVLLR +++ 95 QSMYYPLQLK ++ 98 LLQPPPLLAR ++ 99 KVVDRWNEK ++ 100 RLFTSPIMTK +++ 101 RVFTSSIKTK ++ 102 SVLTSSLVK ++ 104 VLADSVTTK ++ 105 RLFSWLVNR +++ 106 AAFVPLLLK ++ 107 RLQEWKALK +++ 109 KTFTIKRFLAK ++ 110 SAAPPSYFR ++ 256 RTEEVLLTFK ++ 257 VTADHSHVF + 258 GAYAHTVNR +++ 259 KTLELRVAY ++ 260 GTNTVILEY +++ 261 HTFGLFYQR ++ 262 RSRLNPLVQR ++ 263 SSSSATISK ++ 264 AIKVIPTVFK ++ 265 QIHDHVNPK ++ 266 ISYSGQFLVK +++ 267 VTDLISPRK ++ 269 RLKGDAWVYK +++ 270 AVFNPRFYRTY ++ 271 RMFADDLHNLNK +++ 272 RQPERTILRPR ++ 273 RVNAIPFTY +++ 274 KTFPASTVF + 275 STTFPTLTK ++ 276 VSKTTGMEF + 277 TTALKTTSR + 278 NLSSITHER ++ 279 SVSSETTKIKR ++ 280 SVSGVKTTF ++ 281 RAKELEATF + 283 IVQEPTEEK ++ 284 KSLIKSWKK ++ 285 GTVNPTVGK ++ 286 TVAPPQGVVK ++ 287 RRIHTGEKPYK ++

(56) TABLE-US-00018 TABLE 16 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-B*07:02 was ranged by peptide exchange yield: >10% = +; >20% = ++; >50 =+++; >75% = ++++ Seq ID No Sequence Peptide exchange 32 SPNKGTLSV “+++” 33 SPTFHLTL “+++” 34 LPRGPLASLL “+++” 35 FPDNQRPAL “+++” 36 APAAWLRSA “++” 37 RPLFQKSSM “+++” 38 SPHPVTALLTL “+++” 39 RPAPFEVVF “+++” 40 KPGTSYRVTL “+++” 41 RVRSRISNL “+++” 118 SPASRSISL “+++” 119 APLPRPGAVL “+++” 120 RPAMNYDKL “++” 121 VPNQSSESL “+++” 122 YPGFPQSQY “++” 123 KPSESIYSAL “+++” 124 LPSDSHFKITF “+++” 125 VPVYILLDEM “++” 126 KPGPEDKL “++” 127 APRAGSQVV “+++” 128 YPRTITPGM “+++” 129 APRPASSL “+++” 130 FPRLVGPDF “+++” 131 APTEDLKAL “+++” 132 IPGPAQSTI “++” 133 MPNLPSTTSL “+++” 134 RPIVPGPLL “+++” 135 RVRSTISSL “+++” 136 SPFSAEEANSL “+++” 137 SPGATSRGTL “+++” 138 SPMATTSTL “+++” 139 SPQSMSNTL “+++” 140 SPRTEASSAVL “+++” 141 SPMTSLLTSGL “+++” 142 TPGLRETSI “++” 143 SPAMTSTSF “++” 144 SPSPVSSTL “+++” 145 SPSSPMSTF “++” 146 IPRPEVQAL “+++” 147 APRWFPQPTVV “+++” 148 KPYGGSGPL “+++” 149 GPREALSRL “+++” 293 VPDSGATATAY “++” 294 YPLRGSSIF “+++” 295 YPLRGSSIFGL “+++” 296 YPLRGSSI “++” 297 TVREASGLL “+++” 298 YPTEHVQF “++” 299 HPGSSALHY “++” 300 IPMAAVKQAL “+++” 301 SPRRSPRISF “++” 302 RVEEVRALL “+++” 303 LPMWKVTAF “+++” 304 LPRPGAVL “+++” 305 TPWAESSTKF “++” 306 APVIFSHSA “++” 307 LPYGPGSEAAAF “+++” 308 YPEGAAYEF “++” 309 FPQSQYPQY “++++” 311 RPLFYVVSL “++” 312 LPYFREFSM “+++” 313 KVKSDRSVF “+” 314 VPDQPHPEI “+++” 315 SPRENFPDTL “+++” 316 EPKTATVL “++” 317 FPFQPGSV “+++” 318 FPNRLNLEA “+++” 319 SPAEPSVYATL “++++” 320 FPMSPVTSV “+++” 321 SPMDTFLLI “++” 322 SPDPSKHLL “++” 323 RPMPNLRSV “+++” 324 VPYRVVGL “++” 325 GPRNAQRVL “+++” 326 VPSEIDAAF “++” 327 SPLPVTSLI “+++” 328 EPVTSSLPNF “++” 329 FPAMTESGGMIL “+++” 330 FPFVTGSTEM “++” 331 FPHPEMTTSM “+++” 332 FPHSEMTTL “+++” 333 FPHSEMTTVM “+++” 334 FPYSEVTTL “+++” 335 HPDPVGPGL “++” 336 HPKTESATPAAY “++” 337 HPVETSSAL “+++” 338 HVTKTQATF “++” 339 LPAGTTGSLVF “+++” 340 LPEISTRTM “++” 341 LPLDTSTTL “+++” 342 LPLGTSMTF “+++” 343 LPSVSGVKTTF “++” 344 LPTQTTSSL “+++” 345 LPTSESLVSF “++” 346 LPWDTSTTLF “+++” 347 MPLTTGSQGM “++” 348 MPNSAIPFSM “+++” 349 MPSLSEAMTSF “+++” 350 NPSSTTTEF “+++” 351 NVLTSTPAF “++” 352 SPAETSTNM “+++” 353 SPAMTTPSL “+++” 354 SPLPVTSLL “+++” 355 SPLVTSHIM “+++” 356 SPNEFYFTV “+++” 357 SPSPVPTTL “+++” 358 SPSPVTSTL “+++” 359 SPSTIKLTM “+++” 360 SPSVSSNTY “++” 361 SPTHVTQSL “+++” 362 SPVPVTSLF “+++” 363 TAKTPDATF “++” 364 TPLATTQRF “++” 365 TPLATTQRFTY “++” 367 TPSVVTEGF “++” 368 VPTPVFPTM “++” 369 FPHSEMTTV “+++” 370 PGGTRQSL “+” 371 LYVDGFTHW “++” 372 IPRNPPPTLL “+++” 373 RPRALRDLRIL “+++” 374 NPIGDTGVKF “+++” 375 AAASPLLLL “++” 376 RPRSPAGQVA “+++” 377 RPRSPAGQVAAA “+++” 378 RPRSPAGQVAA “+++” 379 GPFPLVYVL “+++” 380 IPTYGRTF “+++” 381 LPEQTPLAF “++” 382 SPMHDRWTF “+++” 383 TPTKETVSL “+++” 384 YPGLRGSPM “++++” 385 SPALHIGSV “+++” 386 FPFNPLDF “++” 387 APLKLSRTPA “+++” 388 SPAPLKLSRTPA “++” 389 SPGAQRTFFQL “+++” 390 NPDLRRNVL “+++” 391 APSTPRITTF “+++” 392 KPIESTLVA “+++”

(57) TABLE-US-00019 TABLE 17 MHC class I binding scores. Binding of HLA-class I restricted peptides to HLA-B*44:02 was measured by peptide exchange yield: >10% = +; >20% = ++; >50 = +++; >75% = ++++ Seq ID No Sequence Peptide exchange 52 AEFLLRIFL “++” 53 MEHPGKLLF “++++” 54 AEITITTQTGY “+++” 55 HETETRTTW “+++” 56 SEPDTTASW “+++” 57 QESDLRLFL “+++” 58 GEMEQKQL “++” 59 SENVTMKVV “+++” 173 AEAQVGDERDY “+++” 174 AEATARLNVF “+++” 175 AEIEPKADG “++” 176 AEIEPKADGSW “+++” 177 TEVGTMNLF “+++” 178 NELFRDGVNW “+++” 179 REAGDEFEL “++” 180 REAGDEFELRY “++” 181 GEGPKTSW “++” 182 KEATEAQSL “+++” 183 YEKGIMQKV “++” 184 AELEALTDLW “+++” 185 AERQPGAASL “++” 186 REGPEEPGL “++” 187 GEAQTRIAW “+++” 188 AEFAKKQPWW “+++” 189 KEFLFNMY “++” 190 YEVARILNL “++” 191 EEDAALFKAW “+++” 192 YEFKFPNRL “+++” 193 LEAQQEAL “++” 194 KEVDPTSHSY “++” 195 AEDKRHYSV “++” 196 REMPGGPVW “+++” 197 AEVLLPRLV “+++” 198 QEAARAAL “++” 199 REIDESLIFY “+++” 200 AESIPTVSF “+++” 201 AETILTFHAF “+++” 202 HESEATASW “+++” 203 IEHSTQAQDTL “++” 204 RETSTSEETSL “+++” 205 SEITRIEM “++” 206 SESVTSRTSY “+++” 207 TEARATSDSW “+++” 208 TEVSRTEAI “++” 209 TEVSRTEL “++” 210 VEAADIFQNF “+++” 211 EEKVFPSPLW “+++” 212 MEQKQLQKRF “+++” 213 KESIPRWYY “++” 214 VEQTRAGSLL “++” 215 SEDGLPEGIHL “++” 396 REASGLLSL “+++” 397 REGDTVQLL “++” 398 SFEQVVNELF “++” 399 RELLHLVTL “+++” 400 GEIEIHLL “+” 402 RELANDELIL “++” 403 EEAQWVRKY “++” 404 NEAIMHQY “++” 405 NEIWTHSY “+” 406 EDGRLVIEF “+” 407 AEHEGVSVL “++” 408 LEKALQVF “++” 409 REFVLSKGDAGL “+++” 410 SEDPSKLEA “+” 411 LELPPILVY “+” 412 QEILTQVKQ “++” 413 IEALSGKIEL “++” 414 EDAALFKAW “++” 415 REEDAALFKAW “+++” 416 SEEETRVVF “+++” 417 AEHFSMIRA “++” 418 FEDAQGHIW “+++” 419 HEFGHVLGL “++” 420 FESHSTVSA “+” 421 GEPATTVSL “++” 422 SETTFSLIF “+++” 423 SEVPTGTTA “++” 424 TEFPLFSAA “+” 425 SEVPLPMAI “+++” 426 PEKTTHSF “+” 427 HESSSHHDL “++” 429 REKFIASVI “++” 431 AEQDPDELNKA “++” 432 EEQYIAQF “+” 433 SDSQVRAF “+” 434 KEAIREHQM “++” 435 REEFVSIDHL “++” 436 REPGDIFSEL “++” 437 TEAVVTNEL “++” 438 SEVDSPNVL “+++”

Example 6

(58) Stability of Peptide-MHC Class I Complexes

(59) Peptide-MHC stability assays for HLA-B*08:01 peptides were performed. The data were obtained using a proximity based, homogenous, real-time assay in order to measure the dissociation of peptides from HLA class I molecules. First, human recombinant HLA-B*08:01 and b2m were expressed in E. coli and purified in a series of liquid chromatography based steps (Ferre et al., 2003; Ostergaard et al., 2001). Then, the stability of a peptide-MHC complex (pMHC) was determined by measuring the amount of b2m associated with the MHC heavy chain over time at 37° C. (Harndahl et al., 2012). The stability of each pMHC, expressed as the half life of b2m associated with the respective heavy chain, was calculated by fitting the data to a one-phase dissociation equation.

(60) The pMHC stabilities were measured in three independent experiments with the peptides in question, and for HLA-B*08:01 were found to span the range from weak-binders (+) to very stable binders (++++). The mean half-life (T1/2) is shown in Table 18.

(61) TABLE-US-00020 TABLE 18 Mean half-life (T1/2) based on three individual measurements. T1/2 > 2 h = +; T1/2 > 4 h = ++; T1/2 > 6 h = +++; T1/2 > 10 h = ++++ Seq ID No Sequence Mean Half-life (T1/2) 43 ALKARTVTF +++ 44 LNKQKVTF ++++ 45 VGREKKLAL ++ 46 DMKKAKEQL + 47 MPNLRSVDL ++ 48 DVKKKIKEV + 49 LPRLKAFMI ++ 50 DMKYKNRV + 51 SLRLKNVQL + 150 MAAVKQAL ++ 151 HLLLKVLAF ++ 152 MGSARVAEL ++ 153 NAMLRKVAV + 154 MLRKIAVAA + 156 HVKEKFLL ++ 157 EAMKRLSYI + 158 LPKLAGLL + 159 VLKHKLDEL + 160 YPKARLAF +++ 161 ALKTTTTAL + 162 QAKTHSTL + 163 QGLLRPVF ++ 164 SIKTKSAEM +++ 166 TPKLRETSI ++ 167 TSHERLTTL ++ 169 TSMPRSSAM +++ 170 YLLEKSRVI ++ 171 FAFRKEAL ++ 172 KLKERNREL +++ 394 MYKMKKPI + 395 VLLPRLVSC +

Example 7

(62) Binding Scores of Selected Peptides for HLA Class II Allotypes

(63) Major histocompatibility complex class II (MHC-II) molecules are predominantly expressed on the surface of professional antigen presenting cells, where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. Peptides presented by the MHC class II molecule bind to a binding groove formed by residues of the MHC α- and β-chain. The peptide-MHC binding affinity is primarily determined by the amino acid sequence of the peptide-binding core. HLA class II binding prediction algorithms are only available for the most important class II alleles and have been tested using the SYFPEITHI algorithm (Rammensee et al., 1999). The algorithm has already been successfully used to identify class I and class II epitopes from a wide range of antigens, e.g. from the human tumor-associated antigens TRP2 (class I) (Sun et al., 2000) and SSX2 (class II) (Neumann et al., 2004). Table 20 shows the HLA class II allotypes which are likely to bind the selected peptides. The peptide was considered as binding to an HLA molecule if the SYFPEITHI score was equal to or higher than 18.

(64) TABLE-US-00021 TABLE 20 Binding of the class II peptides to various HLA class II allotypes. Based on the prediction by the SYFPEITHI algorithm, the selected peptides are likely to bind to at least 4 of the HLA class II allotpyes with known binding motif. Listed are all HLA class II alleles for which a SYFPEITHI prediction matrix is available. Seq Best HLA class II No of HLA ID No Sequence binders HLA Class II binders Class II binder 552 GVNAMLRKVAVAAASKPH DRB1*11:04 DQA1*05:01/DQB1*02:01 (DQ2), 15 VE QA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*13:02, DRB1*15:01 560 PNFSGNWKIIRSENFEELLK DRB1*07:01 DQA1*05:01/DQB1*02:01 (DQ2), 14 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 574 LPDFYNDWMFIAKHLPDL DRB1*11:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*11:01, DRB1*11:04, DRB1*13:02, DRB1*15:01, DRB1*15:02 575 VGDDHLLLLQGEQLRRT DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 8 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*09:01, DRB1*15:01, DRB1*15:02 579 SGGPLVCDETLQGILS DQA1*0501/ DQA1*05:01/DQB1*02:01 (DQ2), 8 DQB1*0201 (DQ2) DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*15:01 582 GSQPWQVSLFNGLSFH DRB1*15:01 DQA1*05:01/DQB1*02:01 (DQ2), 10 DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*07:01, DRB1*09:01, DRB1*15:01, DRB1*15:02 583 LTVKLPDGYEFKFPNRLNL DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 14 EAINY DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 587 DQANLTVKLPDGYEFKFP DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 13 NRLNL DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*11:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 588 VAPDAKSFVLNLGKDSNNL DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 16 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*13:02 590 RVRGEVAPDAKSFVLNLG DRB1*03:01 DQA1*05:01/DQB1*02:01 (DQ2), 10 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*07:01, DRB1*09:01, DRB1*11:04, DRB1*15:01 596 MAADGDFKIKCVAFD DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 10 DQB1*02:01 (DQ2); DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*03:01; DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*07:01 DRB1*08:03, DRB1*09:01, DRB1*15:01 597 SPDAESLFREALSNKVDEL DRB1*07:01 DQA1*05:01/DQB1*02:01 (DQ2), 8 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01 601 LSNKVDELAHFLLRK DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 14 DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*11:01, DRB1*11:04, DRB1*15:01, DRB1*15:02 604 KLITQDLVKLKYLEYRQ DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 9 DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*08:02, DRB1*13:01, DRB1*13:02, DRB1*15:01 605 LTVAEVQKLLGPHVEGLKA DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 EERHRP DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 622 MDALRGLLPVLGQPIIRSIP DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 QGIVA DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*15:01, DRB1*15:02 645 RGLLPVLGQPIIRSIPQGIV DRB1*01:01; DQA1*05:01/DQB1*02:01 (DQ2), 14 AAWRQ DRB1*09:01 DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*15:01, DRB1*15:02 658 VSTMDALRGLLPVLGQPII DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 14 RSIPQG DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*15:01, DRB1*15:02 662 LRTDAVLPLTVAEVQKLLG DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 PHVEG DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 669 VLPLTVAEVQKLLGPHVEG DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 LKAEE DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 672 LRGLLPVLGQPIIRSIPQGI DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 14 VAA DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*15:01, DRB1*15:02 673 IPFTYEQLDVLKHKLDELY DRB1*08:03 DQA1*05:01/DQB1*02:01 (DQ2), 15 PQ DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:02, DRB1*15:01, DRB1*15:02 676 VPPSSIWAVRPQDLDTCDPR DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 10 DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*15:01 679 WGVRGSLLSEADVRALGGLA DRB1*09:01 DQA1*05:01/DQB1*02:01 (DQ2), 12 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*15:01 706 LSTERVRELAVALAQKNVK DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 15 DQB1*03:01 (DQ7) DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 714 AIPFTYEQLDVLKHKLDE DRB1*08:03 DQA1*05:01/DQB1*02:01 (DQ2), 15 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:02, DRB1*15:01, DRB1*15:02 715 GLSTERVRELAVALAQKN DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 15 DQB1*03:01 (DQ7) DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 717 IPQGIVAAWRQRSSRDPS DRB1*11:04 DQA1*05:01/DQB1*02:01 (DQ2), 13 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01 720 ALGGLACDLPGRFVAES DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 8 DQB1*02:01 (DQ2) DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:05, DRB1*11:01, DRB1*11:04 721 RELAVALAQKNVKLSTE DQA1*05:01/ DQA1*05:01/DQB1*03:01 (DQ7), 11 DQB1*03:01 (DQ7) DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*09:01, DRB1*11:04, DRB1*13:01, DRB1*15:01 722 LKALLEVNKGHEMSPQ DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 13 DQB1*02:01(DQ2); DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*01:01; DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05; DRB1*04:05, DRB1*08:03, DRB1*11:01, DRB1*08:03; DRB1*11:04, DRB1*13:01, DRB1*15:01 DRB1*11:04 723 TFMKLRTDAVLPLTVA DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 13 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 727 TLGLGLQGGIPNGYLV DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 9 DQB1*02:01(DQ2); DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*01:01; DRB1*04:02, DRB1*04:04, DRB1*07:01, DRB1*15:01 DRB1*09:01, DRB1*15:01 728 DLPGRFVAESAEVLL DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 12 DQB1*02:01 (DQ2) DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*15:01, DRB1*15:02 732 ERHRPVRDWILRQRQ DRB1*15:01 DQA1*05:01/DQB1*02:01 (DQ2), 4 DRB1*04:01, DRB1*04:04, DRB1*15:01 733 SPRQLLGFPCAEVSG DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 8 DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*15:01, DRB1*15:02 734 SRTLAGETGQEAAPL DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 6 DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*15:01 735 VTSLETLKALLEVNK DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 15 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*15:01, DRB1*15:02 745 WELSQLTNSVTELGPYTLDRD DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 13 DQB1*02:01 (DQ2); DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*13:01, DRB1*15:01, DRB1*15:02 746 EITITTQTGYSLATSQVTLP DRB1*01:01 DQA1*05:01/DQB1*02:01 (DQ2), 10 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*15:01 747 ATTPSWVETHSIVIQGFPH DRB1*07:01 DQA1*05:01/DQB1*02:01 (DQ2), 9 DQA1*05:01/DQB1*03:01 (DQ7), DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*15:01, DRB1*15:02 748 GIKELGPYTLDRNSLYVNG DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 13 DQB1*02:01 (DQ2); DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*01:01 DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*09:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 755 IELGPYLLDRGSLYVNG DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 14 DQB1*02:01 (DQ2) DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*09:01, DRB1*11:04, DRB1*13:02, DRB1*15:01, DRB1*15:02 759 EELGPYTLDRNSLYVNG DRB1*03:01 DQA1*05:01/DQB1*02:01 (DQ2), 12 DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*09:01, DRB1*13:02, DRB1*15:01, DRB1*15:02 760 LKPLFKSTSVGPLYSG DRB1*11:04 DQA1*05:01/DQB1*02:01 (DQ2), 16 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*13:02, DRB1*15:01 764 FDKAFTAATTEVSRTE DQA1*05:01/ DQA1*05:01/DQB1*03:01 (DQ7), 9 DQB1*03:01 (DQ7) DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*15:01 765 ELGPYTLDRDSLYVN DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 11 DQB1*02:01 (DQ2) DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*13:02, DRB1*15:01, DRB1*15:02 766 GLLKPLFKSTSVGPL DRB1*11:04 DQA1*05:01/DQB1*02:01 (DQ2), 16 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*08:02, DRB1*08:03, DRB1*09:01, DRB1*11:01, DRB1*11:04, DRB1*13:01, DRB1*13:02, DRB1*15:01 768 SDPYKATSAVVITST DQA1*05:01/ DQA1*05:01/DQB1*02:01 (DQ2), 10 DQB1*03:01 (DQ7) DQA1*05:01/DQB1*03:01 (DQ7), DQB1*06:02, DRB1*01:01, DRB1*04:01, DRB1*04:04, DRB1*07:01, DRB1*09:01, DRB1*15:01, DRB1*15:02 770 SRKFNTMESVLQGLL DRB1*09:01 DQA1*05:01/DQB1*03:01 (DQ7), 10 DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:04, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*13:02, DRB1*15:01

REFERENCE LIST

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