Identification of promiscuous HLA-DR-restricted CD4⁺ T-cell epitopes on the cancer-testis antigen HCA587

Cancer Sci. 2011 Aug;102(8):1455-61. doi: 10.1111/j.1349-7006.2011.01986.x. Epub 2011 Jun 27.

Abstract

The cancer testis antigen HCA587 is an attractive candidate for T cell-based immunotherapy because it is overexpressed in a wide spectrum of malignant tumors but not normal tissues, except testis. Several CTL epitopes derived from HCA587 have been described. Our aim was to identify helper T lymphocyte epitopes of HCA587 for the optimization of T cell-based immunotherapies against HCA587-expressing tumors. Candidate helper T lymphocyte epitopes for HCA587 were predicted using the SYFPEITHI algorithm and were tested for their ability to induce helper T lymphocyte responses by in vitro peptide vaccination of CD4(+) T lymphocytes from healthy individuals and hepatocellular carcinoma patients. Four CD4(+) T-cell epitopes for HCA587 (p43-57, p145-159, p186-200 and p249-263) were identified. Among them, the p43-57 epitope was shown to be naturally processed and presented by HCA587-expressing tumor cells as well as autologous dendritic cells pulsed with whole-protein HCA587. Notably, this epitope behaved as a promiscuous T-cell epitope as it stimulated T cells in the context of more than one HLA class II allele. Thus, p43-57 is the first HCA587-derived major histocompatibility complex class II-restricted epitope to fulfil all prerequisites for use as a peptide vaccine in patients with HCA587-expressing tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology
  • Cell Line
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-DR Antigens / immunology*
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / immunology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-DR Antigens
  • MAGEC2 protein, human
  • Neoplasm Proteins