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Title: A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.
Austin Authors: Ebert, Lisa M;Liu, Yu Chih;Clements, Craig S;Robson, Neil C;Jackson, Heather M;Markby, Jessica L;Dimopoulos, Nektaria;Tan, Bee Shin;Luescher, Immanuel F;Davis, Ian D;Rossjohn, Jamie;Cebon, Jonathan S ;Purcell, Anthony W;Chen, Weisan
Affiliation: Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 27-Jan-2009
Publication information: Cancer Research 2009; 69(3): 1046-54
Abstract: 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.
Gov't Doc #: 19176376
DOI: 10.1158/0008-5472.CAN-08-2926
Type: Journal Article
Subjects: Alanine.genetics
Amino Acid Sequence
Amino Acid Substitution
Antigen Presentation
Antigens, Neoplasm.immunology
CD8-Positive T-Lymphocytes.immunology
Cancer Vaccines.immunology.therapeutic use
Cell Line, Tumor
HLA-B Antigens.immunology
HLA-B7 Antigen
Immunodominant Epitopes.immunology
Lymphocyte Activation
Membrane Proteins.immunology
Models, Molecular
Molecular Sequence Data
Peptide Fragments.immunology
Protein Conformation
Appears in Collections:Journal articles

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