title: A WT1 protein-derived, naturally processed 16-mer peptide, WT1(332), is a promiscuous helper peptide for induction of WT1-specific Th1-type CD4(+) T cells.
abstract: The Wilms' tumor gene WT1 is overexpressed in various tumors, and the WT1 protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. A WT1 protein-derived 16-mer peptide, WT1(332) (KRYFKLSHLQMHSRKH), which was naturally generated through processing in cells and could elicit Th1-type CD4(+) helper T cell responses with an HLA-DRB1*0405-restriction has previously been identified by us. In the present study, it has been demonstrated that WT1(332) can induce WT1(332)-specific CD4(+) T cell responses with the restriction of not only HLA-DRB1*0405 but also HLA-DRB1*1501, -DRB1*1502, or -DPB1*0901. These HLA class II-restricted WT1(332)-specific CD4(+) T cell lines produced IFN-gamma but neither IL-4 nor IL-10 with WT1(332) stimulation, thus showing a Th1-type cytokine profile. Furthermore, HLA-DRB1*1501 or -DRB1*1502-restricted WT1(332)-specific CD4(+) T cell lines responded to WT1-expressing transformed cells in an HLA-DRB1-restricted manner, which is consistent with our previous finding that WT1(332) is a naturally processed peptide. These results indicate that the natural peptide, WT1(332), is a promiscuous WT1-specific helper epitope. WT1(332) is expected to apply to cancer patients with various types of HLA class II as a WT1-specific helper peptide in combination with HLA class I-restricted WT1 peptides.
authors.affiliation: Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Fujiki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Oka
authors.forename: Mai
authors.initials: M
authors.lastname: Kawakatsu
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tsuboi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nakajima
authors.forename: Olga A
authors.initials: OA
authors.lastname: Elisseeva
authors.forename: Yukie
authors.initials: Y
authors.lastname: Harada
authors.forename: Zheyu
authors.initials: Z
authors.lastname: Li
authors.forename: Naoko
authors.initials: N
authors.lastname: Tatsumi
authors.forename: Eriko
authors.initials: E
authors.lastname: Kamino
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shirakata
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Nishida
authors.forename: Yuki
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oji
authors.forename: Haruo
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation; D009842:Oligopeptides / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D025721:WT1 Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D009842:Oligopeptides; D025721:WT1 Proteins; C520525:WT1(332)(KRYFKLSHLQMHSRKH)