| Autor: |
Tomita, Yusuke, Yuno, Akira, Tsukamoto, Hirotake, Senju, Satoru, Kuroda, Yasuhiro, Hirayama, Masatoshi, Imamura, Yuya, Yatsuda, Junji, Sayem, Mohammad Abu, Irie, Atsushi, Hamada, Akinobu, Jono, Hirofumi, Yoshida, Koji, Tsunoda, Takuya, Daigo, Yataro, Kohrogi, Hirotsugu, Yoshitake, Yoshihiro, Nakamura, Yusuke, Shinohara, Masanori, Nishimura, Yasuharu |
| Zdroj: |
OncoImmunology; March 2014, Vol. 3 Issue: 3 |
| Abstrakt: |
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. |
| Databáze: |
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