title: Immune responses to Mycobacterial heat shock protein 70 accompany self-reactivity to human BiP in rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease, and a member of human heat shock protein (HSP) 70 protein family, Binding Immunoglobulin Protein (BiP), has been identified as an important autoantigen for T and B cells. We herein focused on Mycobacterial (Myc) HSPs and immune responses to MycHSPs in RA patients. Serum titers of antibodies against MycHSP70 were significantly elevated in RA patients and correlated with serum anti-BiP antibody titers. A MycHSP70-derived HLA-DR4 major epitope was identified using the proliferative capacity of RA PBMCs as an indicator. The major epitope, MycHSP70287-306, was located at the corresponding position in the major epitope for human BiP336-355, and a strong correlation was found between the proliferation of PBMCs in response to MycHSP70287-306 and BiP336-355. The immunization of HLA-DR4 transgenic mice with MycHSP70 induced the proliferation of T cells and development of anti-BiP antibodies. In contrast, the oral administration of MycHSP70287-306 resulted in the amelioration of collagen-induced arthritis, serum antibody responses, and T cell proliferation. In conclusion, immune responses to MycHSP70 were associated with adaptive immunity against BiP in RA, and could be an important mechanism underlying the development of autoimmunity.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shoda
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Hanata
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sumitomo
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D015804:HLA-DR4 Antigen / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008222:Lymphokines / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D009161:Mycobacterium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D015804:HLA-DR4 Antigen; D018840:HSP70 Heat-Shock Proteins; D008222:Lymphokines; C013059:immunoglobulin-binding factors