Survey of naturally occurring CD4+ T cell responses against NY-ESO-1 in cancer patients: correlation with antibody responses.
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.
Gnjatic
Sacha
S
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. gnjatics@mskcc.org
Atanackovic
Djordje
D
Jäger
Elke
E
Matsuo
Mitsutoshi
M
Selvakumar
Annamalai
A
Altorki
Nasser K
NK
Maki
Robert G
RG
Dupont
Bo
B
Ritter
Gerd
G
Chen
Yao-Tseng
YT
Knuth
Alexander
A
Old
Lloyd J
LJ
D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000097:blood*; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000235:genetics; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011506:Proteins; D011994:Recombinant Proteins