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

Int J Cancer. 1995 Jul 4;62(1):97-102. doi: 10.1002/ijc.2910620118.

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 gp 100 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 gp 100 protein. Apart from the peptide corresponding to gp 100 amino acids 457-466, we identified the gp 100 peptide 154-162 as a second epitope recognized by TIL 1200. A 100-fold lower concentration of this novel gp 100 peptide was required for target-cell sensitization compared to peptide 457-466, indicating that the 154-162 peptide is the dominant gp 100 epitope for TIL 1200. Together with the recently described gp 100 280-288 epitope, 3 distinct CTL epitopes have now been identified in gp 100, all presented in the context of HLA-A2.1. Therefore, gp 100 is an attractive target antigen in the development of immuno-therapeutic protocols against melanoma.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Epitopes*
  • HLA-A Antigens / analysis*
  • Humans
  • Melanoma / immunology*
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / immunology*
  • Molecular Sequence Data
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / immunology*
  • Peptide Fragments / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured
  • gp100 Melanoma Antigen

Substances

  • Epitopes
  • HLA-A Antigens
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • gp100 Melanoma Antigen