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.

Autor:	Tomita Y; 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., Yuno A; 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., Tsukamoto H; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Senju S; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Kuroda Y; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Hirayama M; 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., Imamura Y; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Yatsuda J; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Sayem MA; 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., Irie A; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Hamada A; Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan., Jono H; Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan., Yoshida K; 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., Tsunoda T; 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., Daigo Y; 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., Kohrogi H; Department of Respiratory Medicine; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Yoshitake Y; Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Nakamura Y; Department of Clinical Pharmaceutical Sciences; Graduate School of Pharmaceutical Sciences; Kumamoto University; Kumamoto, Japan ; Department of Medicine; University of Chicago; Chicago, IL USA., Shinohara M; Department of Oral and Maxillofacial Surgery; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan., Nishimura Y; Department of Immunogenetics; Graduate School of Medical Sciences; Kumamoto University; Kumamoto, Japan.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2014 Mar 27; Vol. 3, pp. e28100. Date of Electronic Publication: 2014 Mar 27 (Print Publication: 2014).
DOI:	10.4161/onci.28100
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 LY6K 172-191 -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 LY6K 172-191 -LP in vitro and in vivo. In addition, LY6K 172-191 -LP enhanced induction of LY6K-specific CTLs among the peripheral blood mononuclear cells (PBMCs) of head-and-neck malignant tumor (HNMT) patients. LY6K 172-191 -LP-specific Th1 immunologic response following 1 week in vitro stimulation of PBMCs with LY6K 172-191 -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 LY6K 172-191 -LP for the induction and propagation of both LY6K-specific Th1 cells and CTLs.
Databáze:	MEDLINE
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