Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses

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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DOI: 10.1073/pnas.1133324100


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
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