Identification of a novel NY-ESO-1 promiscuous helper epitope presented by multiple MHC class II molecules found frequently in the Japanese population

Cancer Sci. 2007 Jul;98(7):1092-8. doi: 10.1111/j.1349-7006.2007.00501.x. Epub 2007 May 4.

Abstract

NY-ESO-1 is a cancer-testis antigen that elicits strong cellular and humoral immune responses against NY-ESO-1-expressing tumors. Although CD4(+) T cells play a critical role in inducing antitumor immunity, little is known about MHC class II-restricted helper epitopes of the NY-ESO-1 antigen compared with MHC class I-restricted epitopes. Here, we searched for new NY-ESO-1 helper epitopes presented by MHC class II molecules, especially those found frequently in the Japanese population. We established five NY-ESO-1-specific helper T-cell lines from healthy Japanese donors using NY-ESO-1 recombinant protein and peptide. Using MHC class II-specific antibodies and a panel of Epstein-Barr virus-transformed B-cell lines, it was demonstrated that four out of the five T-cell lines recognized a region within NY-ESO-1(119-143) in the context of HLA-DRB1*0802, DRB1*0901, DRB1*1502 or DRB1*0405/*0410. In addition, using a set of overlapping 15-mer synthetic peptides, we found that NY-ESO-1(122-138) was a promiscuous region that bound to four distinct HLA-DR molecules found in the Japanese population. These findings expand the usefulness of NY-ESO-1 as a tool for tumor vaccine therapy in eliciting NY-ESO-1-specific helper T-cell responses, especially in Japanese cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology*
  • Asian Continental Ancestry Group
  • CD4-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology
  • Cell Line
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Epitopes / analysis
  • HLA-D Antigens / analysis*
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / chemistry
  • HLA-DRB1 Chains
  • Humans
  • Japan
  • Membrane Proteins / chemistry
  • Membrane Proteins / immunology*
  • Molecular Sequence Data
  • Neoplasms / immunology
  • Peptide Fragments / chemistry
  • T-Lymphocytes / immunology*

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Epitopes
  • HLA-D Antigens
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Membrane Proteins
  • Peptide Fragments