IDENTIFICATION OF THE IMMUNODOMINANT PEPTIDES OF THE MART-1 HUMAN-MELANOMA ANTIGEN RECOGNIZED BY THE MAJORITY OF HLA-A2-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-rela ted protein-1 (gp75) were evaluated for recognition by HLA-A2-restrict ed melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the t umor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recog nized MART-1), but none of the TIL recognized tyrosinase or gp75. Base d on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART- 1 were synthesized in an attempt to identify the epitopes recognized b y TIL. Three peptides were recognized by TIL, when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in se nsitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this pepti de appears to be a very common immunogenic epitope for HLA-A2-restrict ed melanoma-specific TIL and may be useful for the development of immu notherapeutic strategies.