Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen

Details

Serval ID
serval:BIB_ACB4DFB29D71
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen
Journal
Clinical Immunology
Author(s)
Valmori  D., Levy  F., Godefroy  E., Scotto  L., Souleimanian  N. E., Karbach  J., Tosello  V., Hesdorffer  C. S., Old  L. J., Jager  E., Ayyoub  M.
ISSN
1521-6616 (Print)
Publication state
Published
Issued date
02/2007
Volume
122
Number
2
Pages
163-72
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb
Abstract
Identification of immunodominant CD8(+) T cell responses to frequently expressed tumor antigens across MHC class I polymorphism is essential for the implementation of cancer immunotherapy. However, the key factors that determine immunodominance are not fully understood. Because of its frequent expression in tumors and its spontaneous immunogenicity, NY-ESO-1 is a prime target of cancer vaccines and an ideal model antigen for elucidating the molecular basis of immunodominant tumor-specific CD8(+) T cell responses. Here, we have assessed CD8(+)T cell responses to full-length NY-ESO-1 in cancer patients. We identified 3 immunodominant regions of the protein located within 3 distinct clusters of MHC class I binding sequences that co-localize with previously defined clusters of MHC class II binding sequences, are predicted to be hydrophobic and undergo efficient proteasomal processing. Our results support the concept that epitope clustering within defined protein regions identifies tumor antigen immunodominant regions and suggest a general strategy for their identification.
Keywords
Antigen Presentation/*immunology Antigens, Neoplasm/immunology/*metabolism CD8-Positive T-Lymphocytes/enzymology/immunology Cancer Vaccines/therapeutic use Cells, Cultured Epitopes, T-Lymphocyte/*metabolism Humans Immunodominant Epitopes/*metabolism Membrane Proteins/immunology/*metabolism Proteasome Endopeptidase Complex/*metabolism T-Lymphocytes, Cytotoxic/enzymology/*immunology
Pubmed
Web of science
Create date
28/01/2008 11:17
Last modification date
20/08/2019 15:16
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