Human heat shock protein 70 peptide complexes specifically activate antimelanoma T cells

Cancer Res. 2001 Jan 1;61(1):222-7.

Abstract

Members of the heat shock protein 70 (HSP70) family display a broad cellular localization and thus bind a repertoire of chaperoned peptides potentially derived from proteins of different cellular compartments. In this report, we show that HSP70 purified from human melanoma can activate T cells recognizing melanoma differentiation antigens in an antigen- and HLA class I-dependent fashion. HLA class I-restricted anti-melanoma T cells were susceptible to MHC-restricted, HSP70-dependent stimulation, indicating that HSP70 complexed peptides were able to gain access to the class I HLA presentation pathway. In addition, MHC matching between the melanoma cells used as a source of HSP and the responding T cells were not required, indicating that HSP70 activation may occur across MHC barriers. Besides the MHC-restricted and peptide-dependent activation pathway, HSP70 with no endogenous complexed peptides or HSP70 purified from antigen-negative cells was also able to induce IFN-gamma release by antimelanoma T cells by a MHC-independent mechanism. In this case, however, higher doses of HSP70 were required. The capacity to activate class I-restricted, antitumor T cells as well as antigen-presenting cells, together with the finding that the HSP70 chaperoned peptide repertoire includes melanoma-shared epitopes, holds promise for a HSP70-based cancer vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / immunology
  • Antigens, Neoplasm / immunology
  • Cross Reactions
  • Epitopes, T-Lymphocyte / immunology
  • HLA Antigens / immunology
  • HSP70 Heat-Shock Proteins / immunology*
  • HSP70 Heat-Shock Proteins / isolation & purification
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / pharmacology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lymphocyte Activation / immunology
  • Melanoma / chemistry
  • Melanoma / immunology*
  • Molecular Chaperones / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • HSP70 Heat-Shock Proteins
  • Histocompatibility Antigens Class I
  • Molecular Chaperones