Identification of HER2/neu-derived peptide epitopes recognized by gastric cancer-specific cytotoxic T lymphocytes

Int J Cancer. 1998 Oct 5;78(2):202-8. doi: 10.1002/(sici)1097-0215(19981005)78:2<202::aid-ijc14>;2-c.


We have derived HLA-A2.1-restricted, gastric cancer-specific cytotoxic T lymphocyte (CTL) lines by repetitive in vitro stimulation of tumor-associated lymphocytes (TAL) with autologous tumor cells. The HER2/neu specificity of these gastric cancer-specific CTLs was demonstrated using HER2/neu-transfected cell lines and HER2/neu-expressing tumors, and with a set of HER2/neu-derived peptide epitopes. Gastric cancer-specific CTLs specifically lysed autologous and allogeneic HLA-A2.1+, HER2/neu+ gastric cancer cells, HER2/neu-transfected C1R/A2 cell lines (HLA-A2.1+, HER2+) and HLA-A2.1-transfected SW626 tumor cell lines (HLA-A2.1+, HER2+). This recognition could be inhibited by anti-HLA-A2 antibody or by cold target HER2/neu-transfected C1R/A2 cells. Our results demonstrate that the HER2/neu-encoded HLA-A2.1-associated epitopes recognized by CTLs are presented as naturally processed peptides on gastric cancer lines. Furthermore, 3 of 19 tested HER2/neu-derived peptide epitopes [HER2(9(106)), HER2(9(369)), HER2(9(689))], which all bound HLA-A2.1 with high (IC50 < 50 nM) affinity, were able to sensitize HLA-A2+ C1R/A2 cells to be recognized by the gastric cancer-specific CTLs, demonstrating the immunodominance of these epitopes. In conclusion, our findings implicate HER2/neu-derived epitopes as potential candidates for novel immunotherapy and vaccine strategies against gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HLA-A2 Antigen / immunology
  • Humans
  • Immunodominant Epitopes / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • Sensitivity and Specificity
  • Stomach Neoplasms / immunology*
  • Stomach Neoplasms / pathology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured


  • HLA-A2 Antigen
  • Immunodominant Epitopes
  • Receptor, ErbB-2