Gnjatic, S., Atanackovic, D., Jager, E., Matsuo, M., Selvakumar, A., Altorki, N. K., Maki, R. G., Dupont, B., Ritter, G., Chen, Y. T., Knuth, A., Old, L. J. (July 2003) Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses. Proc Natl Acad Sci U S A, 100 (15). pp. 8862-7. ISSN 0027-8424 (Print)0027-8424 (Linking)
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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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Amino Acid Sequence Antibodies, Neoplasm/*blood Antigen Presentation *Antigens, Neoplasm/genetics CD4-Positive T-Lymphocytes/*immunology Epitopes/genetics Female Histocompatibility Antigens Class II/metabolism Humans Immunization In Vitro Techniques Lymphocyte Activation Melanoma/immunology *Membrane Proteins Molecular Sequence Data Neoplasms/*immunology Ovarian Neoplasms/immunology Proteins/genetics/*immunology Recombinant Proteins/genetics/immunology |
| Subjects: | diseases & disorders > cancer diseases & disorders > immune system diseases bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > immunoglobulin proteins |
| CSHL Authors: | |
| Communities: | CSHL labs > Maki lab |
| Depositing User: | Matt Covey |
| Date: | 22 July 2003 |
| Date Deposited: | 26 Oct 2016 21:21 |
| Last Modified: | 09 Nov 2017 17:15 |
| PMCID: | PMC166404 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33648 |
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