Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen

H. Kobayashi, M. Wood, Y. Song, E. Appella, E. Celis

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

It is accepted that both helper and CTLs play a critical role in immune antitumor responses. Thus, the design of effective immune-based therapies for cancer relies in the identification of relevant tumor-associated antigens (TAAs) capable of eliciting strong helper and cytotoxic T-cell responses against tumor cells. The product of the HER2/neu oncogene is considered as a prototype TAA, because it is found overexpressed in a large variety of malignancies, whereas normal cells only produce low levels of this product. Several cytotoxic T-cell epitopes for HER2/neu have been identified that enable the design of peptide-based therapeutic vaccines for tumors expressing this TAA. Nevertheless, it is expected that inclusion of peptide epitopes capable of eliciting HER2/neu-specific T helper responses into these vaccines may enhance their effectiveness in the clinic. We describe here a strategy to identify helper T-cell epitopes for HER2/neu that focuses on peptides predicted to bind to numerous histo-compatibility alleles (promiscuous epitopes), which would encourage their use in therapeutic vaccines for the general cancer patient population. Following this approach, we successfully identified several peptides that elicited T helper (CD4+) proliferative responses to peptides derived from HER2/neu. Most of the T-cell responses appeared to reflect a low affinity for antigen, which could be the result of immune tolerance because HER2/neu is expressed in low levels in normal cells and possibly including lymphocytes and monocytes. Interestingly, one of these peptides, HER2883, was recognized by T cells in the context of either HLA-DR1, HLA-DR4, HLA-DR52, and HLA-DR53, indicating a high degree of histocompatibility promiscuity. Furthermore, T cells that reacted with peptide HER2883 could also recognize antigen-presenting cells that process HER2/neu recombinant protein. These results may be relevant for the design of more effective therapeutic vaccines for tumors expressing the HER2/neu oncogene product.

Original languageEnglish (US)
Pages (from-to)5228-5236
Number of pages9
JournalCancer Research
Volume60
Issue number18
StatePublished - Sep 15 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kobayashi, H., Wood, M., Song, Y., Appella, E., & Celis, E. (2000). Defining promiscuous MHC class II helper T-cell epitopes for the HER2/neu tumor antigen. Cancer Research, 60(18), 5228-5236.