CD4(+) T cell recognition of MHC class II-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production.
NY-ESO-1 is a tumor-specific shared antigen with distinctive immunogenicity. Both CD8(+) T cells and class-switched Ab responses have been detected from patients with cancer. In this study, a CD4(+) T cell line was generated from peripheral blood mononuclear cells of a melanoma patient and was shown to recognize NY-ESO-1 peptides presented by HLA-DP4, a dominant MHC class II allele expressed in 43--70% of Caucasians. The ESO p157--170 peptide containing the core region of DP4-restricted T cell epitope was present in a number of tumor cell lines tested and found to be recognized by both CD4(+) T cells as well as HLA-A2-restricted CD8(+) T cells. Thus, the ESO p157--170 epitope represents a potential candidate for cancer vaccines aimed at generating both CD4(+) and CD8(+) T cell responses. More importantly, 16 of 17 melanoma patients who developed Ab against NY-ESO-1 were found to be HLA-DP4-positive. CD4(+) T cells specific for the NY-ESO-1 epitopes were generated from 5 of 6 melanoma patients with NY-ESO-1 Ab. In contrast, no specific DP4-restricted T cells were generated from two patients without detectable NY-ESO-1 Ab. These results suggested that NY-ESO-1-specific DP4-restricted CD4(+) T cells were closely associated with NY-ESO-1 Ab observed in melanoma patients and might play an important role in providing help for activating B cells for NY-ESO-1-specific Ab production.
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
G
G
Zeng
X
X
Wang
P F
PF
Robbins
S A
SA
Rosenberg
R F
RF
Wang
D000483:Alleles; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000276:immunology*
D000906:Antibodies; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D015789:HLA-A2 Antigen; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; C056284:HLA-DPw4 antigen; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011506:Proteins