One NY-ESO-1-derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma.
NY-ESO-1 is expressed by a broad range of human tumors and is often recognized by Abs in the sera of cancer patients with NY-ESO-1-expressing tumors. The NY-ESO-1 gene also encodes several MHC class I- and class II-restricted tumor epitopes recognized by T lymphocytes. In this study we report one novel pan-MHC class II-restricted peptide sequence, NY-ESO-1 87-111, that is capable of binding to multiple HLA-DR and HLA-DP4 molecules, including HLA-DRB1*0101, 0401, 0701, and 1101 and HLA-DPB1*0401 and 0402 molecules. We also demonstrate that peptide NY-ESO-1 87-111 stimulates Th1-type and Th-2/Th0-type CD4(+) T cells and clones when presented in the context of these HLA-DR and HLA-DP4 molecules. Both bulk CD4(+) T cells and CD4(+) T cell clones were capable of recognizing not only peptide-pulsed APCs, but also autologous dendritic cells, either loaded with the NY-ESO-1 protein or transfected with NY-ESO-1 cDNAs. Using IFN-gamma and IL-5 ELISPOT assays and PBL from patients with NY-ESO-1-expressing tumors, we observed the existence of Th1-type circulating CD4(+) T cells recognizing peptide NY-ESO-1 87-111 in the context of HLA-DP4 molecules. Taken together, these data represent the first report of an HLA-DR- and HLA-DP-restricted epitope from a tumor Ag. They also support the relevance of cancer vaccine trials with peptides NY-ESO-1 87-111 in the large number of cancer patients with NY-ESO-1-expressing tumors.
Mandic
Maja
M
Department of Medicine and The Melanoma Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Castelli
Florence
F
Janjic
Bratislav
B
Almunia
Christine
C
Andrade
Pedro
P
Gillet
Daniel
D
Brusic
Vladimir
V
Kirkwood
John M
JM
Maillere
Bernard
B
Zarour
Hassane M
HM
D000483:Alleles; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006682:HLA-DP Antigens / Q000276:immunology / Q000378:metabolism*; D059868:HLA-DP beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016056:Immunodominant Epitopes / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; C056284:HLA-DPw4 antigen; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D008565:Membrane Proteins; D010446:Peptide Fragments