Defining MHC class II T helper epitopes for WT1 tumor antigen

Hiroya Kobayashi, Toshihiro Nagato, Naoko Aoki, Keisuke Sato, Shoji Kimura, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The product of Wilms' tumor gene 1 (WT1) is overexpressed in diverse human tumors, including leukemia, lung and breast cancer, and is often recognized by antibodies in the sera of patients with leukemia. Since WT1 encodes MHC class I-restricted peptides recognized by cytotoxic T lymphocytes (CTL), WT1 has been considered as a promising tumor-associated antigen (TAA) for developing anticancer immunotherapy. In order to carry out an effective peptide-based cancer immunotherapy, MHC class II-restricted epitope peptides that elicit anti-tumor CD4+ helper T lymphocytes (HTL) will be needed. In this study, we analyzed HTL responses against WT1 antigen using HTL lines elicited by in vitro immunization of human lymphocytes with synthetic peptides predicted to serve as HTL epitopes derived from the sequence of WT1. Two peptides, WT1 124-138 and WT1247-261, were shown to induce peptide-specific HTL, which were restricted by frequently expressed HLA class II alleles. Here, we also demonstrate that both peptides-reactive HTL lines were capable of recognizing naturally processed antigens presented by dendritic cells pulsed with tumor lysates or directly by WT1 + tumor cells that express MHC class II molecules. Interestingly, the two WT1 HTL epitopes described here are closely situated to known MHC class I-restricted CTL epitopes, raising the possibility of stimulating CTL and HTL responses using a relatively small synthetic peptide vaccine. Because HTL responses to TAA are known to be important for promoting long-lasting anti-tumor CTL responses, the newly described WT1 T-helper epitopes could provide a useful tool for designing powerful vaccines against WT1-expressing tumors.

Original languageEnglish (US)
Pages (from-to)850-860
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume55
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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  • Cite this

    Kobayashi, H., Nagato, T., Aoki, N., Sato, K., Kimura, S., Tateno, M., & Celis, E. (2006). Defining MHC class II T helper epitopes for WT1 tumor antigen. Cancer Immunology, Immunotherapy, 55(7), 850-860. https://doi.org/10.1007/s00262-005-0071-0