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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
Author(s) -
Fujiki Fumihiro,
Oka Yoshihiro,
Kawakatsu Mai,
Tsuboi Akihiro,
Nakajima Hiroko,
Elisseeva Olga A.,
Harada Yukie,
Li Zheyu,
Tatsumi Naoko,
Kamino Eriko,
Shirakata Toshiaki,
Nishida Sumiyuki,
Taniguchi Yuki,
Kawase Ichiro,
Oji Yusuke,
Sugiyama Haruo
Publication year - 2008
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2008.00080.x
Subject(s) - biology , epitope , peptide , human leukocyte antigen , t cell , immunotherapy , cancer research , microbiology and biotechnology , antigen , immunology , immune system , biochemistry
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‐γ 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.