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

S Gnjatic, D Atanackovic, E Jäger… - Proceedings of the …, 2003 - National Acad Sciences
S Gnjatic, D Atanackovic, E Jäger, M Matsuo, A Selvakumar, NK Altorki, RG Maki, B Dupont…
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 …
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.
National Acad Sciences