A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.

Details

Serval ID
serval:BIB_2AB102155DD8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.
Journal
Cancer research
Author(s)
Ebert L.M., Liu Y.C., Clements C.S., Robson N.C., Jackson H.M., Markby J.L., Dimopoulos N., Tan B.S., Luescher I.F., Davis I.D., Rossjohn J., Cebon J., Purcell A.W., Chen W.
ISSN
1538-7445[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
69
Number
3
Pages
1046-1054
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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.
Keywords
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
Pubmed
Web of science
Open Access
Yes
Create date
15/01/2010 15:24
Last modification date
20/08/2019 13:10
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