Article: article from journal or magazin.
Identification of five new HLA-B*3501-restricted epitopes derived from common melanoma-associated antigens, spontaneously recognized by tumor-infiltrating lymphocytes.
Journal of Immunology
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Animals, Antigen Presentation, Antigens, Neoplasm/chemistry, Antigens, Neoplasm/immunology, COS Cells, Cell Division/immunology, Cell Line, Transformed, Cell Line, Tumor, Clone Cells, Cytotoxicity Tests, Immunologic, Epitopes, T-Lymphocyte/immunology, Epitopes, T-Lymphocyte/isolation & purification, HLA-B35 Antigen/immunology, HLA-B35 Antigen/isolation & purification, Humans, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, MART-1 Antigen, Melanoma/enzymology, Melanoma/immunology, Membrane Glycoproteins/immunology, Membrane Glycoproteins/metabolism, Membrane Proteins, Mice, Monophenol Monooxygenase/immunology, Monophenol Monooxygenase/metabolism, Neoplasm Proteins/immunology, Neoplasm Proteins/metabolism, Peptide Fragments/chemistry, Peptide Fragments/immunology, Protein Binding/immunology, Proteins/immunology, Proteins/metabolism, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/pathology, gp100 Melanoma Antigen
Web of science
Last modification date