title: Experimental myositis inducible with transfer of dendritic cells presenting a skeletal muscle C protein-derived CD8 epitope peptide.
abstract: It is suggested that polymyositis, an autoimmune inflammatory myopathy, is mediated by autoaggressive CD8 T cells. Skeletal muscle C protein is a self-antigen that induces C protein-induced myositis, a murine model of polymyositis. To establish a new murine model of myositis inducible with a single CD8 T-cell epitope peptide that derives from the C protein, three internet-based prediction systems were employed to identify 24 candidate peptides of the immunogenic fragment of the C protein and bind theoretically to major histocompatibility complex class I molecules of C57BL/6 (B6) mice. RMA-S cell assay revealed that a HILIYSDV peptide, amino acid position 399-406 of the C protein, had the highest affinity to the H2-K(b) molecules. Transfer of mature bone marrow-derived dendritic cells pulsed with HILIYSDV induced myositis in naive B6 mice. This myositis was suppressed by anti-CD8-depleting antibodies but not by anti-CD4-depleting antibodies. Because this myositis model is mediated by CD8 T cells independently of CD4 T cells, it should be a useful tool to investigate pathology of polymyositis and develop therapies targeting CD8 T cells.
authors.affiliation: Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan Japan Society for the Promotion of Science, Tokyo 102-0083, Japan Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045, Japan Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibarakii 305-8575, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okiyama
authors.affiliation: Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Hisanori
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
authors.forename: Takatoku
authors.initials: T
authors.lastname: Oida
authors.affiliation: Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Hirata
authors.affiliation: Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Yokozeki
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibarakii 305-8575, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.affiliation: Department of Rheumatology, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Kanagawa 230-0045, Japan Global Center of Excellence Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo 113-8519, Japan kohsaka.rheu@tmd.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kohsaka
mesh_terms: D000818:Animals; D002097:C-Reactive Protein / Q000737:chemistry* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000737:chemistry / Q000276:immunology*; D009220:Myositis / Q000276:immunology* / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D002097:C-Reactive Protein
keywords: CD4 T cell; RMA-S cell; bone marrow-derived dendritic cell