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Identification of immunogenic LY6K long peptide encompassing both CD4+ and CD8+ T-cell epitopes and eliciting CD4+ T-cell immunity in patients with malignant disease.


ABSTRACT: Identification of peptides that activate both tumor-specific helper T (Th) cells and cytotoxic T lymphocytes (CTLs) are important for the induction of effective antitumor immune responses. We focused on a long peptide (LP) derived from lymphocyte antigen 6 complex locus K (LY6K) encompassing both candidate Th epitopes and a known CTL epitope. Using IFNγ ELISPOT assays as a marker of activated T cells, we studied the immunogenicity and cross-priming potential of LY6K-LP, assaying human immune cell responses in vitro and immunologic activities in HLA-A24 transgenic mice in vivo. We identified LY6K172-191-LP as an effective immunogen spanning naturally processed epitopes recognized by T helper type 1 (Th1) cells and CTLs. LY6K-specific CTLs were induced through cross-presentation of LY6K172-191-LP in vitro and in vivo. In addition, LY6K172-191-LP enhanced induction of LY6K-specific CTLs among the peripheral blood mononuclear cells (PBMCs) of head-and-neck malignant tumor (HNMT) patients. LY6K172-191-LP-specific Th1 immunologic response following 1 week in vitro stimulation of PBMCs with LY6K172-191-LP were detected in 16 of 21 HNMT patients (76%) vaccinated with CTL-epitope peptides and 1 of 11 HNMT patients (9%) prior to vaccination, but not in 9 healthy donors. Our results are the first to demonstrate the presence of LY6K-specific Th1 cell responses in HNMT patients and underscore the possible utility of LY6K172-191-LP for the induction and propagation of both LY6K-specific Th1 cells and CTLs.

SUBMITTER: Tomita Y 

PROVIDER: S-EPMC4203508 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identification of immunogenic LY6K long peptide encompassing both CD4<sup>+</sup> and CD8<sup>+</sup> T-cell epitopes and eliciting CD4<sup>+</sup> T-cell immunity in patients with malignant disease.

Tomita Yusuke Y   Yuno Akira A   Tsukamoto Hirotake H   Senju Satoru S   Kuroda Yasuhiro Y   Hirayama Masatoshi M   Imamura Yuya Y   Yatsuda Junji J   Sayem Mohammad Abu MA   Irie Atsushi A   Hamada Akinobu A   Jono Hirofumi H   Yoshida Koji K   Tsunoda Takuya T   Daigo Yataro Y   Kohrogi Hirotsugu H   Yoshitake Yoshihiro Y   Nakamura Yusuke Y   Shinohara Masanori M   Nishimura Yasuharu Y  

Oncoimmunology 20140327


Identification of peptides that activate both tumor-specific helper T (Th) cells and cytotoxic T lymphocytes (CTLs) are important for the induction of effective antitumor immune responses. We focused on a long peptide (LP) derived from lymphocyte antigen 6 complex locus K (LY6K) encompassing both candidate Th epitopes and a known CTL epitope. Using IFNγ ELISPOT assays as a marker of activated T cells, we studied the immunogenicity and cross-priming potential of LY6K-LP, assaying human immune cel  ...[more]

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