NY-ESO-1 is expressed by a broad range of human
tumors and is often recognized by Abs in the sera of
cancer patients with NY-ESO-1-expressing
tumors. The NY-ESO-1 gene also encodes several MHC class I- and class II-restricted
tumor epitopes recognized by T lymphocytes. In this study we report one novel pan-MHC class II-restricted
peptide sequence, NY-ESO-1 87-111, that is capable of binding to multiple
HLA-DR and
HLA-DP4 molecules, including
HLA-DRB1*0101, 0401, 0701, and 1101 and
HLA-DPB1*0401 and 0402 molecules. We also demonstrate that
peptide NY-ESO-1 87-111 stimulates Th1-type and Th-2/Th0-type CD4(+) T cells and clones when presented in the context of these
HLA-DR and
HLA-DP4 molecules. Both bulk CD4(+) T cells and CD4(+) T cell clones were capable of recognizing not only
peptide-pulsed APCs, but also autologous dendritic cells, either loaded with the NY-ESO-1
protein or transfected with NY-ESO-1 cDNAs. Using IFN-gamma and
IL-5 ELISPOT assays and PBL from patients with NY-ESO-1-expressing
tumors, we observed the existence of Th1-type circulating CD4(+) T cells recognizing
peptide NY-ESO-1 87-111 in the context of
HLA-DP4 molecules. Taken together, these data represent the first report of an
HLA-DR- and
HLA-DP-restricted
epitope from a
tumor Ag. They also support the relevance of
cancer vaccine trials with
peptides NY-ESO-1 87-111 in the large number of
cancer patients with NY-ESO-1-expressing
tumors.