Identification of a novel peptide derived from the melanocyte‐specific gp100 antigen as the dominant epitope recognized by an HLA‐A2.1‐restricted anti‐melanoma CTL line

Cytotoxic T lymphocytes (CTL) reactive with human melanoma tumor cells occasionally display cross‐reactivity with normal melanocytes. Previously, we identified the melanocyte lineage‐specific antigen gp100 that is expressed by both melanoma cells and normal melanocytes, as a target antigen for tumor‐infiltrating lymphocytes derived from a melanoma patient (TIL 1200). Here, we demonstrate that the oligoclonal HLA‐A2.1‐restricted TIL 1200 line is reactive with 2 distinct peptides derived from the gpl00 protein. Apart from the peptide corresponding to gpl00 amino acids 457–466, we identified the gpl00 peptide 154–162 as a second epitope recognized by TIL 1200. A 100‐fold lower concentration of this novel gpl00 peptide was required for target‐cell sensitization compared to peptide 457–466, indicating that the 154–162 peptide is the dominant gpl00 epitope for TIL 1200. Together with the recently described gpl00 280–288 epitope, 3 distinct CTL epitopes have now been identified in gpl00, all presented in the context of HLA‐A2.1. Therefore, gpl00 is an attractive target antigen in the development of immuno‐therapeutic protocols against melanoma. © 1995 Wiley‐Liss Inc.