A Natural Cytotoxic T Cell Response in a Spontaneously Regressing Human Melanoma Targets a Neoantigen Resulting From a Somatic Point Mutation

Eur J Immunol. 1999 Feb;29(2):592-601. doi: 10.1002/(SICI)1521-4141(199902)29:02<592::AID-IMMU592>3.0.CO;2-2.

Abstract

We have studied a case of human primary melanoma displaying the classical signs of a spontaneous regression in order to characterize potentially efficient anti-tumor T cell responses. In a previous series of experiments a unique TCR Vbeta16+ T cell was shown to be highly expanded at the tumor site. The corresponding clone was isolated in vitro and found to be a CD8+ cytotoxic T lymphocyte with a strong and selective cytolytic activity against the autologous tumor cell line. Here, we demonstrate that this predominant Vbeta16+ tumor-infiltrating lymphocyte recognizes a peptide encoded by a novel unconventional myosin class I gene. This peptide includes a mutation due to a single nucleotide substitution. The resulting Glu-->Lys replacement at position 911 of the coding sequence is critical to generate the recognized T cell epitope. These experiments demonstrate the existence of a natural tumor-specific cytolytic T cell response in a primary regressing human melanoma lesion.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Cytotoxicity, Immunologic*
  • DNA, Complementary / genetics
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Melanoma / immunology*
  • Melanoma / pathology
  • Molecular Sequence Data
  • Neoplasm Regression, Spontaneous / immunology*
  • Point Mutation
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / pathology
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • DNA, Complementary