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Tumor Biology |
Department of Medicine and Melanoma Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213 [H. M. Z., J. M. K., E. W.]; Department of Surgery and Molecular Genetics and Biochemistry, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261[W. J. S.]; and Kent Ridge Digital Labs, Singapore 119613 [V. B.]
The NY-ESO-1 gene is expressed by a range of human
tumors and encodes HLA-A2-restricted melanoma peptides recognized by
CD8+ CTLs. Here we report that the NY-ESO-1 gene also
encodes two overlapping, but non-cross-reactive,
HLA-DRB1*0401-presented peptides that are recognized by CD4+ T cells.
The NY-ESO-1119–143 peptide was able to induce specific
CD4+ T cells in vitro from both an
HLA-DRB1*0401+ normal donor and an
HLA-DRB1*0401+ patient with melanoma. Bulk and cloned CD4+
T cells produced IFN-
specifically in response to, and also lysed,
T2.DR4 cells pulsed with peptide NY-ESO-1119–143 and the
autologous tumor cell line, but not a DRB1*0401+ melanoma
cell line that does not express NY-ESO-1. Interestingly, the
NY-ESO119–143 peptide contains two overlapping putative
"core" epitopes recognized by non-cross-reactive
anti-NY-ESO-1119–143 CD4+ T-cell clones. Taken together,
these data support the use of this novel DR4-restricted tumor peptide,
NY-ESO-1119–143, or its two "sub-epitopes" in
immunotherapeutic trials designed to generate or enhance specific CD4+
T-cell responses against tumors expressing NY-ESO-1 in
vivo.
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