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Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes.

Yutaka Kawakami, S Eliyahu, Kazuyasu Sakaguchi, Paul Robbins, Licia Rivoltini, John R. Yannelli, Ettore Appella, S A Rosenberg

The Journal of Experimental Medicine · 1994 · 865 citations · 26 references

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TL;DR

The study synthesized 23 MART‑1 peptides to pinpoint HLA‑A2‑restricted epitopes recognized by tumor‑infiltrating lymphocytes. Researchers tested HLA‑A2‑restricted CTLs from 10 patients against four melanoma proteins and then pulsed T2 target cells with the synthesized MART‑1 peptides to assess TIL recognition. Nine of ten TILs recognized MART‑1, and the peptide AAGIGILTV was identified as a highly immunogenic epitope, recognized by 9/10 HLA‑A2‑restricted melanoma‑specific CTLs.

Abstract

Four melanoma proteins, MART-1, gp100, tyrosinase, and tyrosinase-related protein-1 (gp75) were evaluated for recognition by HLA-A2-restricted melanoma-specific cytotoxic T lymphocytes (CTLs) derived from the tumor-infiltrating lymphocytes (TIL) of 10 different patients. 9 of 10 TIL recognized MART-1, 4 recognized gp100 (including 3 that also recognized MART-1), but none of the TIL recognized tyrosinase or gp75. Based on the known HLA-A2.1 peptide binding motifs, 23 peptides from MART-1 were synthesized in an attempt to identify the epitopes recognized by TIL. Three peptides were recognized by TIL when pulsed on T2 target cells. One of the 9-mer peptides, AAGIGILTV, was most effective in sensitizing the T2 cells for TIL lysis. This peptide was recognized by 9 of 10 HLA-A2-restricted melanoma-specific CTLs. Therefore, this peptide appears to be a very common immunogenic epitope for HLA-A2-restricted melanoma-specific TIL and may be useful for the development of immunotherapeutic strategies.