Identification of a WT1 protein-derived peptide, WT1, as a HLA-A 0206-restricted, WT1-specific CTL epitope.
The Wilms' tumor gene WT1 is overexpressed in various kinds of hematopoietic malignancies as well as solid cancers, and this protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. WT1-specific CTL epitopes with a restriction of HLA-A 2402 or HLA-A 0201 have been already identified. In the present study it has been demonstrated that a 9-mer WT1-derived WT1(187) peptide, which had already been shown to elicit a WT1-specific CTL response with a restriction of HLA-A 0201, can also elicit a CTL response with a restriction of HLA-A 0206. In all three different HLA-A 0206(+) healthy donors examined, WT1(187) peptide-specific CTL could be generated from peripheral blood mononuclear cells, and the CTL showed cytotoxic activity that depended on dual expression of WT1 and HLA-A 0206 molecules. The present study describes the first identification of a HLA-A 0206-restricted, WT1-specific CTL epitope. The present results should help to broaden the application of WT1 peptide-based immunotherapy from only HLA-A 0201-positive to HLA-A 0206-positive cancer patients as well.
Li
Zheyu
Z
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Oka
Yoshihiro
Y
Tsuboi
Akihiro
A
Fujiki
Fumihiro
F
Harada
Yukie
Y
Nakajima
Hiroko
H
Masuda
Tomoki
T
Fukuda
Yoko
Y
Kawakatsu
Mai
M
Morimoto
Soyoko
S
Katagiri
Takamasa
T
Tatsumi
Naoya
N
Hosen
Naoki
N
Shirakata
Toshiaki
T
Nishida
Sumiyuki
S
Kawakami
Yutaka
Y
Udaka
Keiko
K
Kawase
Ichiro
I
Oji
Yusuke
Y
Sugiyama
Haruo
H
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016162:Genes, Wilms Tumor; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D009842:Oligopeptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D025721:WT1 Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C526286:HLA-A*02:06 antigen; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D025721:WT1 Proteins