Article: article from journal or magazin.
A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design.
Alanine/genetics, Amino Acid Sequence, Amino Acid Substitution, Antigen Presentation, Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Cancer Vaccines/therapeutic use, Cell Line, Tumor, HLA-B Antigens/immunology, Humans, Immunodominant Epitopes/immunology, Lymphocyte Activation, Melanoma/immunology, Melanoma/therapy, Membrane Proteins/immunology, Models, Molecular, Molecular Sequence Data, Peptide Fragments/immunology, Protein Conformation
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