Identification of an antigenic peptide derived from the cancer-testis antigen NY-ESO-1 binding to a broad range of HLA-DR subtypes.
NY-ESO-1 is a SEREX-defined cancer-testis antigen of which several MHC I, but only few MHC II-restricted epitopes have been identified. Searching for highly promiscuous MHC II-restricted peptides that might be suitable as a CD4+ stimulating vaccine for many patients, we used the SYFPEITHI algorithm and identified an NY-ESO-1-derived pentadecamer epitope (p134-148) that induced specific CD4+ T-cell responses restricted to the HLA-DRB1 subtypes *0101, *0301, *0401, and *0701 that have a cumulative prevalence of 40% in the Caucasian population. The DR restriction of the p134-148 pentadecamer was demonstrated by inhibition with an HLA-DR antibody and a functional peptide displacement titration assay with the pan-DR-binding T-helper epitope PADRE as the competitor. The natural processing and presentation of this epitope was demonstrated by recognition of an NY-ESO-1+ melanoma cell line by T cells with specificity for p134-148. The pentadecamer p134-148 was able to induce CD4+ responses in 4/38 cancer patients tested. However, no strict correlation was found between CD4+ T-cell responses against p134-148 reactivity and anti-NY-ESO-1 antibody titers in the serum of patients, suggesting that CD4+ and B-cell responses are regulated independently. In conclusion, p134-148 holds promise as a broadly applicable peptide vaccine for patients with NY-ESO-1-positive neoplasms.
Neumann
Frank
F
Med. Klinik I, Saarland University Medical School, 66421 Homburg, Germany.
Wagner
Claudia
C
Kubuschok
Boris
B
Stevanovic
Stefan
S
Rammensee
Hans-Georg
HG
Pfreundschuh
Michael
M
D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology*; D008654:Mesothelioma / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D010997:Pleural Neoplasms / Q000276:immunology / Q000473:pathology; D011485:Protein Binding
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D010446:Peptide Fragments