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Identification of CDCA1‐derived long peptides bearing both CD4 + and CD8 + T‐cell epitopes: CDCA1‐specific CD4 + T‐cell immunity in cancer patients
Author(s) -
Tomita Yusuke,
Yuno Akira,
Tsukamoto Hirotake,
Senju Satoru,
Yoshimura Sachiko,
Osawa Ryuji,
Kuroda Yasuhiro,
Hirayama Masatoshi,
Irie Atsushi,
Hamada Akinobu,
Jono Hirofumi,
Yoshida Koji,
Tsunoda Takuya,
Kohrogi Hirotsugu,
Yoshitake Yoshihiro,
Nakamura Yusuke,
Shinohara Masanori,
Nishimura Yasuharu
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28376
Subject(s) - epitope , ctl* , cytotoxic t cell , immunogenicity , cd8 , biology , immunology , t cell , antigen , human leukocyte antigen , peripheral blood mononuclear cell , immune system , microbiology and biotechnology , in vitro , biochemistry
We recently identified a novel cancer‐testis antigen, cell division cycle associated 1 (CDCA1) using genome‐wide cDNA microarray analysis, and CDCA1‐derived cytotoxic T lymphocyte (CTL)‐epitopes. In this study, we attempted to identify CDCA1‐derived long peptides (LPs) that induce both CD4 + helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II‐binding peptides with CDCA1‐derived CTL‐epitope sequences presented by HLA‐A2 ( A*02:01 ) or HLA‐A24 ( A*24:02 ) to select candidate CDCA1‐LPs encompassing both Th cell epitopes and CTL‐epitopes. We studied the immunogenicity of CDCA1‐LPs and the cross‐priming potential of LPs bearing CTL‐epitopes in both human in vitro and HLA‐class I transgenic mice in vivo . Then we analyzed the Th cell response to CDCA1 in head‐and‐neck cancer (HNC) patients before and after vaccination with a CDCA1‐derived CTL‐epitope peptide using IFN‐γ enzyme‐linked immunospot assays. We identified two CDCA1‐LPs, CDCA1 39–64 ‐LP and CDCA1 55–78 ‐LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1‐specific CTLs were induced through cross‐presentation of CDCA1‐LPs in vitro and in vivo . In addition, CDCA1‐specific Th cells enhanced induction of CDCA1‐specific CTLs. Furthermore, significant frequencies of CDCA1‐specific Th cell responses were detected after short‐term in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1‐LPs in HNC patients (CDCA1 39–64 ‐LP, 74%; CDCA1 55–78 ‐LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1‐specific Th cell responses in HNC patients and underline the possible utility of CDCA1‐LPs for propagation of both CDCA1‐specific Th cells and CTLs.