In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 15 ( 2003-07-22), p. 8862-8867
Abstract:
NY-ESO-1 is one of the most immunogenic proteins described in human
cancers, based on its capacity to elicit simultaneous antibody and CD8 + T cell responses in vivo . Although HLA class II
restricted epitopes from NY-ESO-1 have been identified, no broad survey has yet established the status of natural CD4 + T cell responses in
cancer patients in relation to CD8 + and antibody responses. We used
a recently developed general strategy for monitoring CD4 + responses
that overcomes the need for prior knowledge of epitope or HLA restriction to analyze a series of 31 cancer patients and healthy donors for the presence of
CD4 + T cells to NY-ESO-1, and related this response to NY-ESO-1
expression in tumor cells and serum antibodies to NY-ESO-1. None of the 18 patients that tested seronegative for NY-ESO-1 had detectable CD4 + T cell responses. On the contrary, 11 of 13 cancer patients with serum
antibodies to NY-ESO-1 had polyclonal CD4 + T cell responses directed against various known and previously undescribed NY-ESO-1 epitopes.
NY-ESO-1 peptide 80–109 was the most immunogenic, with 10 of 11 patients responding to this peptide. We show here that 12-mer determinants from
NY-ESO-1 eliciting a CD4 + T cell response were peptide 87–98
with promiscuous HLA class II presentation, peptide 108–119 restricted by HLA-DP4, and peptides 121–132 and 145–156, both shorter
epitopes from previously described HLA-DR4 peptides, also presented by HLA-DR7. This study represents the next step in compiling a comprehensive
picture of the adaptive immune response to NY-ESO-1, and provides a general strategy for analyzing the CD4 + T cell response to other tumor
antigens eliciting a humoral immune response.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1133324100
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2003
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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