title: Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease.
abstract: T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirota
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of Frontier Research in Tumor Immunology, Center of Medical Innovation and Translational Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Naganari
authors.initials: N
authors.lastname: Ohkura
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Morikawa
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Department of Frontier Research in Tumor Immunology, Center of Medical Innovation and Translational Research, Osaka University, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Furu
authors.affiliation: Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Geriatric and Environmental Dermatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Geriatric and Environmental Dermatology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Akimichi
authors.initials: A
authors.lastname: Morita
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Dario A A
authors.initials: DA
authors.lastname: Vignali
authors.affiliation: Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA. Howard Hughes Medical Institute, National Jewish Health, Denver, CO 80206, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan. Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan. shimon@ifrec.osaka-u.ac.jp.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012269:Ribosomal Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D004268:DNA-Binding Proteins; C486191:RPL23a protein, human; C499308:Rag2 protein, mouse; D011948:Receptors, Antigen, T-Cell; D012269:Ribosomal Proteins; C486193:Rpl23 protein, mouse