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[Cancer Research 61, 7577-7584, October 15, 2001]
© 2001 American Association for Cancer Research

Immunology

Identification of Helper T-Cell Epitopes That Encompass or Lie Proximal to Cytotoxic T-Cell Epitopes in the gp100 Melanoma Tumor Antigen1

Hiroya Kobayashi, Jun Lu and Esteban Celis2

Department of Immunology and Cancer Center, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905

The melanocyte-associated antigen gp100 constitutes one of the most attractive targets for T-cell-based immunotherapy against malignant melanoma. Although several MHC class I-restricted epitopes have been identified for CTLs, thus far, only one MHC class II T helper epitope (restricted by HLA-DR4) has been described in the literature. Using an algorithm to identify promiscuous helper T-cell epitopes, here we describe three additional MHC class II-restricted epitopes from gp100. Whereas one T helper epitope, gp100175–189, was restricted by the HLA-DR53 and DQw6 alleles, the T-cell responses to two other epitopes, gp10074–89 and gp100576–590, were restricted by HLA-DR7. Most interestingly, the newly identified helper T lymphocyte epitopes encompass or lie proximal to previously described CTL epitopes for this tumor-associated antigen. Together with the previously described HLA-DR4-restricted epitope, these T helper epitopes offer coverage for the majority of the human population. Moreover, the use of peptide vaccines containing both CTLs and T helper epitopes could offer therapeutic advantages over current approaches that focus solely on eliciting antitumor CTL responses.




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