Identification of a shared HLA-A*0201-restricted T-cell epitope from the melanoma antigen tyrosinase-related protein 2 (TRP2).
Tyrosinase-related protein 2 (TRP2) is a melanosomal enzyme expressed in most mammalian melanocytes and melanomas. This protein has been identified as a melanoma antigen recognized by tumor reactive CTLs derived from tumor infiltrating lymphocytes in the context of HLA-A31 and HLA-A33. The frequencies of these HLA-A alleles among melanoma patients in the United States is low (approximately 6% for HLA-A31 and approximately 2% for HLA-A33) compared with that of HLA-A*0201 (approximately 46%). Therefore, to extend significantly the use of TRP2-based immunotherapies for the treatment of patients with melanoma, we searched for new HLA-A*0201-restricted epitopes from this protein by screening TRP2-derived peptides for the induction of melanoma-reactive CTL. Fifty-one peptides were selected from TRP2 based on a permissive HLA-A*0201 binding motif, and the 21 peptides with the highest experimentally determined binding affinities were used to stimulate peripheral blood lymphocytes from HLA-A*0201+ melanoma patients in vitro. One peptide, TRP2(180-188) (SVYDFFVWL), induced CTLs from three of four patients that specifically recognized peptide-pulsed T2 cells, COS-7 cells expressing HLA-A*0201 and TRP2, and HLA-A2+ TRP2+ melanomas. TRP2(180-188) is identical to a previously identified TRP2 epitope recognized by murine melanoma-reactive CTLs in the context of H-2Kb. These results suggest that TRP2 may be useful for the development of murine tumor immunotherapy models and for the treatment of melanoma patients who are diverse in HLA expression.
Parkhurst
M R
MR
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892-1502, USA. Maria_Parkhurst@nih.gov
Fitzgerald
E B
EB
Southwood
S
S
Sette
A
A
Rosenberg
S A
SA
Kawakami
Y
Y
D000951:Antigens, Neoplasm / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010446:Peptide Fragments; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase