NY-ESO-1 119-143 is a promiscuous major histocompatibility complex class II T-helper epitope recognized by Th1- and Th2-type tumor-reactive CD4+ T cells.
The NY-ESO-1 gene product is expressed by a range of human tumors and is recognized by antibodies from sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and MHC class II-restricted tumor epitopes recognized by T lymphocytes. In particular, we previously reported that the NY-ESO-1 119-143 peptide contains at least two HLA-DRB1*0401-presented epitopes that are recognized by melanoma-reactive CD4+ T cells. Here we report that the NY-ESO-1 119-143 peptide can be presented in the context of multiple HLA-DR alleles to stimulate tumor-reactive CD4+ T cells. The NY-ESO-1 119-143 peptide is able to bind to several DR molecules. The NY-ESO-1 119-143 peptide is also capable of inducing specific CD4+ T cells in vitro from peripheral blood lymphocytes of normal donors and patients with melanoma who express these HLA-DR alleles. These CD4+ T cells recognize NY-ESO-1(+), HLA-matched or autologous melanoma cell lines, as well as autologous antigen-presenting cells fed with the NY-ESO-1 protein. We also demonstrate that the NY-ESO-1 119-143 peptide stimulates in vitro both Th1-type and Th2-type CD4+ T-cell responses from peripheral blood lymphocytes of normal donors and melanoma patients. Taken together, these data suggest a key role of the NY-ESO-1 119-143 peptide sequence in the induction of cellular and humoral responses against NY-ESO-1-expressing tumors. They support the relevance of cancer vaccine trials with the NY-ESO-1 119-143 peptide in the large number of cancer patients with NY-ESO-1-expressing tumors.
Zarour
Hassane M
HM
Department of Medicine and Melanoma Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA. zarourhm@msx.upmc.edu
Maillere
Bernard
B
Brusic
Vladimir
V
Coval
Kara
K
Williams
Eileen
E
Pouvelle-Moratille
Sandra
S
Castelli
Florence
F
Land
Stephanie
S
Bennouna
Jaafar
J
Logan
Theodore
T
Kirkwood
John M
JM
D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008565:Membrane Proteins; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011506:Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins