Identification of helper T-cell epitopes that encompass or lie proximal to cytotoxic T-cell epitopes in the gp100 melanoma tumor antigen.
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, gp100(175-189), was restricted by the HLA-DR53 and DQw6 alleles, the T-cell responses to two other epitopes, gp100(74-89) and gp100(576-590), 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.
Kobayashi
H
H
Department of Immunology and Cancer Center, Mayo Clinic and Mayo Graduate School, Rochester, Minnesota 55905, USA.
Lu
J
J
Celis
E
E
D000465:Algorithms; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D015809:HLA-DR7 Antigen / Q000235:genetics / Q000276:immunology; D059845:HLA-DRB4 Chains; D006801:Humans; D008545:Melanoma / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; C063831:HLA-DQ6 antigen; D006684:HLA-DR Antigens; C050610:HLA-DR53; D015809:HLA-DR7 Antigen; D059845:HLA-DRB4 Chains; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D058951:gp100 Melanoma Antigen