title: Identification of an HLA-A2-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2).
abstract: We herein report the identification of an HLA-A2 supertype-restricted epitope peptide derived from hypoxia-inducible protein 2 (HIG2), which is known to be a diagnostic marker and a potential therapeutic target for renal cell carcinoma. Among several candidate peptides predicted by the HLA-binding prediction algorithm, HIG2-9-4 peptide (VLNLYLLGV) was able to effectively induce peptide-specific cytotoxic T lymphocytes (CTLs). The established HIG2-9-4 peptide-specific CTL clone produced interferon-γ (IFN-γ) in response to HIG2-9-4 peptide-pulsed HLA-A*02:01-positive cells, as well as to cells in which HLA-A*02:01 and HIG2 were exogenously introduced. Moreover, the HIG2-9-4 peptide-specific CTL clone exerted cytotoxic activity against HIG2-expressing HLA-A*02:01-positive renal cancer cells, thus suggesting that the HIG2-9-4 peptide is naturally presented on HLA-A*02:01 of HIG-2-expressing cancer cells and is recognized by CTLs. Furthermore, we found that the HIG2-9-4 peptide could also induce CTLs under HLA-A*02:06 restriction. Taken together, these findings indicate that the HIG2-9-4 peptide is a novel HLA-A2 supertype-restricted epitope peptide that could be useful for peptide-based immunotherapy against cancer cells with HIG2 expression.
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan ; OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan ; OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan ; Laboratory of Molecular Medicine Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan ; OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Osawa
authors.affiliation: OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Harada
authors.affiliation: OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: OncoTherapy Science Inc, Research and Development Division, Kanagawa, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Hikichi
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Miyazawa
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Masaji
authors.initials: M
authors.lastname: Tani
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Iwahashi
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Laboratory of Molecular Medicine Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan ; Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima, Japan.
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Laboratory of Molecular Medicine Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan ; Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; C405620:HILPDA protein, human; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D009363:Neoplasm Proteins; D010455:Peptides; D007371:Interferon-gamma