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

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Abstract
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.