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

C. Castelli, A. T. Ciupitu, F. Rini, L. Rivoltini, A. Mazzocchi, R. Kiessling, G. Parmiani

Research output: Contribution to journalArticlepeer-review

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 antimelanoma 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-γ 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.

Original languageEnglish
Pages (from-to)222-227
Number of pages6
JournalCancer Research
Volume61
Issue number1
Publication statusPublished - Jan 1 2001

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Human heat shock protein 70 peptide complexes specifically activate antimelanoma t cells'. Together they form a unique fingerprint.

Cite this