Identification of five new HLA-B*3501-restricted epitopes derived from common melanoma-associated antigens, spontaneously recognized by tumor-infiltrating lymphocytes.
We previously described HLA-B35-restricted melanoma tumor-infiltrating lymphocyte responses to frequently expressed melanoma-associated Ags: tyrosinase, Melan-A/MART-1, gp100, MAGE-A3/MAGE-A6, and NY-ESO-1. Using clones derived from these TIL, we identified in this study the corresponding epitopes. We show that five of these epitopes are new and that melanoma cells naturally present all the six epitopes. Interestingly, five of these epitopes correspond to or encompass melanoma-associated Ag epitopes presented in other HLA contexts, such as A2, A1, B51, and Cw3. In particular, the HLA-B35-restricted Melan-A epitope is mimicked by the peptide 26-35, already known as the most immunodominant melanoma epitope in the HLA-A*0201 context. Because this peptide lacked adequate anchor amino acid residues for efficient binding to HLA-B35, modified peptides were designed. Two of these analogues were found to induce higher PBL- and tumor-infiltrating lymphocyte-specific responses than the parental peptide, suggesting that they could be more immunogenic in HLA-B*3501 melanoma patients. These data have important implications for the formulation of polypeptide-based vaccines as well as for the monitoring of melanoma-specific CTL response in HLA-B*3501 melanoma patients.
Benlalam
Houssem
H
Unit Institut National de la Santé et de la Recherche Médicale Unité 463, Nantes, France.
Linard
Boris
B
Guilloux
Yannik
Y
Moreau-Aubry
Agnès
A
Derré
Laurent
L
Diez
Elisabeth
E
Dreno
Brigitte
B
Jotereau
Francine
F
Labarrière
Nathalie
N
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D019556:COS Cells; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002999:Clone Cells; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D015797:HLA-B35 Antigen / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism*; D058965:MART-1 Antigen; D008545:Melanoma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D014442:Monophenol Monooxygenase / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D058951:gp100 Melanoma Antigen
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D015797:HLA-B35 Antigen; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; C489519:Mageb3 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; C548642:Pmel protein, mouse; D011506:Proteins; D058951:gp100 Melanoma Antigen; D014442:Monophenol Monooxygenase