title: 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.
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Respiratory Medicine; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yuno
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Hirotake
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Hirayama
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Imamura
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yatsuda
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Biotechnology and Genetic Engineering; Mawlana Bhashani Science and Technology University; Tangail, Bangladesh.
authors.forename: Mohammad Abu
authors.initials: MA
authors.lastname: Sayem
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Irie
authors.affiliation: Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Hamada
authors.affiliation: Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Jono
authors.affiliation: Laboratory of Molecular Medicine; Human Genome Center; Institute of Medical Science; The University of Tokyo; Tokyo, Japan ; OncoTherapy Science Incorporation; Research and Development Division; Kanagawa, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Laboratory of Molecular Medicine; Human Genome Center; Institute of Medical Science; The University of Tokyo; Tokyo, Japan ; OncoTherapy Science Incorporation; Research and Development Division; Kanagawa, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Laboratory of Molecular Medicine; Human Genome Center; Institute of Medical Science; The University of Tokyo; Tokyo, Japan ; Department of Medical Oncology and Cancer Center; Shiga University of Medical Science; Otsu, Japan.
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.affiliation: Department of Respiratory Medicine; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kohrogi
authors.affiliation: Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshitake
authors.affiliation: Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Medicine; University of Chicago; Chicago, IL USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
keywords: CTL epitope; Th1 cells; cancer testis antigen; cross-presentation; cross-priming; head and neck cancer; helper T-cell epitope; immunotherapy; lymphocyte antigen 6 complex locus K