TY - JOUR
T1 - Identification of helper T-cell epitopes that encompass or lie proximal to cytotoxic T-cell epitopes in the gp100 melanoma tumor antigen
AU - Kobayashi, H.
AU - Lu, J.
AU - Celis, E.
PY - 2001/10/15
Y1 - 2001/10/15
N2 - 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.
AB - 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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M3 - Article
C2 - 11606397
AN - SCOPUS:0035887163
VL - 61
SP - 7577
EP - 7584
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 20
ER -