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PMID: 15085202 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An immunodominant SSX-2-derived epitope recognized by CD4+ T cells in association with HLA-DR.

The Journal of clinical investigation ·Vol. 113 ·No. 8 ·2004-04-00 ·Pages 1225-33

Ayyoub M, Hesdorffer CS, Montes M, Merlo A, Speiser D, Rimoldi D, Cerottini JC, Ritter G, Scanlan M, Old LJ, Valmori D

Abstract

Ectopic gene expression in tumors versus normal somatic tissues provides opportunities for the specific immunotargeting of cancer cells. SSX gene products are expressed in tumors of different histological types and can be recognized by tumor-reactive CTLs from cancer patients. Here, we report the identification of an SSX-2-derived immunodominant T cell epitope recognized by CD4(+) T cells from melanoma patients in association with HLA-DR. The epitope maps to the 37-58 region of the protein, encompassing the sequence of the previously defined HLA-A2-restricted immunodominant epitope SSX-2(41-49). SSX-2(37-58)-specific CD4(+) T cells were detected among circulating lymphocytes from the majority of melanoma patients analyzed and among tumor-infiltrating lymphocytes, but not in healthy donors. Together, our data suggest a dominant role of the 37-58 sequence in the induction of cellular CD4(+) T cell responses against SSX antigens and will be instrumental for both the onset and the monitoring of upcoming cancer-vaccine trials using SSX-derived immunogens.

MeSH Terms
Amino Acid Sequence CD4-Positive T-Lymphocytes/immunology Cancer Vaccines/immunology Epitopes, T-Lymphocyte HLA-DR Antigens/immunology HLA-DRB1 Chains Humans Immunodominant Epitopes Melanoma/immunology Molecular Sequence Data Neoplasm Proteins/immunology Peptide Fragments/immunology Repressor Proteins/immunology
Chemicals
Cancer Vaccines Epitopes, T-Lymphocyte HLA-DR Antigens HLA-DRB1 Chains Immunodominant Epitopes Neoplasm Proteins Peptide Fragments Repressor Proteins synovial sarcoma X breakpoint proteins
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Ayyoub Maha
Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Hesdorffer Charles S
Montes Monica
Merlo Andrea
Speiser Daniel
Rimoldi Donata
Cerottini Jean-Charles
Ritter Gerd
Scanlan Matthew
Old Lloyd J
Valmori Danila
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI20667
Published
2004-04-00
Pages
1225-33
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC385406
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI20667 PMC Full Text View journal details
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