title: Identification of a novel NY-ESO-1 promiscuous helper epitope presented by multiple MHC class II molecules found frequently in the Japanese population.
abstract: NY-ESO-1 is a cancer-testis antigen that elicits strong cellular and humoral immune responses against NY-ESO-1-expressing tumors. Although CD4(+) T cells play a critical role in inducing antitumor immunity, little is known about MHC class II-restricted helper epitopes of the NY-ESO-1 antigen compared with MHC class I-restricted epitopes. Here, we searched for new NY-ESO-1 helper epitopes presented by MHC class II molecules, especially those found frequently in the Japanese population. We established five NY-ESO-1-specific helper T-cell lines from healthy Japanese donors using NY-ESO-1 recombinant protein and peptide. Using MHC class II-specific antibodies and a panel of Epstein-Barr virus-transformed B-cell lines, it was demonstrated that four out of the five T-cell lines recognized a region within NY-ESO-1(119-143) in the context of HLA-DRB1*0802, DRB1*0901, DRB1*1502 or DRB1*0405/*0410. In addition, using a set of overlapping 15-mer synthetic peptides, we found that NY-ESO-1(122-138) was a promiscuous region that bound to four distinct HLA-DR molecules found in the Japanese population. These findings expand the usefulness of NY-ESO-1 as a tool for tumor vaccine therapy in eliciting NY-ESO-1-specific helper T-cell responses, especially in Japanese cancer patients.
authors.affiliation: Division of Immunoregulation, Section of Disease Control, Hokkaido University, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Keiko
authors.initials: K
authors.lastname: Tsuji
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamagishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsubara
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D044466:Asian People; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000032:analysis; D006681:HLA-D Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis / Q000737:chemistry; D059811:HLA-DRB1 Chains; D006801:Humans; D007564:Japan; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008565:Membrane Proteins; D010446:Peptide Fragments