Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses Journal Article
| Authors: | Gnjatic, S.; Atanackovic, D.; Jäger, E.; Matsuo, M.; Selvakumar, A.; Altorki, N. K.; Maki, R. G.; Dupont, B.; Ritter, G.; Chen, Y. T.; Knuth, A.; Old, L. J. |
| Article Title: | Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: Correlation with antibody responses |
| 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. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; cancer patient; neoplasms; ovarian neoplasms; proteins; melanoma; protein; membrane proteins; tumor antigen; antigen presentation; lymphocyte activation; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; hla antigen class 2; antibody response; cd4-positive t-lymphocytes; recombinant proteins; epitope; cd4 antigen; histocompatibility antigens class ii; humoral immunity; antibodies, neoplasm; antigen presenting cell; t lymphocyte activation; immunization; epitopes; hla dp antigen; ny eso 1 protein; hla dp4 antigen; polyclonal activation; humans; human; female; priority journal; article; hla dr4 antigen; hla dr7 antigen |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 100 |
| Issue: | 15 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2003-07-22 |
| Start Page: | 8862 |
| End Page: | 8867 |
| Language: | English |
| DOI: | 10.1073/pnas.1133324100 |
| PUBMED: | 12853579 |
| PROVIDER: | scopus |
| PMCID: | PMC166404 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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