Characterization of pathogenic T cells and autoantibodies in C-protein-induced autoimmune polymyositis.
Although autoimmune processes may take place in human polymyositis, little is known with regard to its pathogenesis due to the lack of appropriate animal models. In the present study, we developed experimental autoimmune myositis (EAM) in Lewis rats by immunization with recombinant skeletal C-protein and examined the role of pathogenic T cells and autoantibodies. Using recombinant proteins and synthetic peptides, we demonstrated that skeletal C-protein Fragment 2 (SC2) has the strongest myositis-inducing ability and that myositis-inducing epitope(s) reside within the residues 334-363 of SC2 (SC2P3). However, immunization with SC2P3 induced only mild EAM compared with SC2 immunization. Characterization of T cells and antisera revealed that SC2P3 and SC2P7 contain the B cell epitope, while the T cell epitope resides in SC2P5. Furthermore, anti-SC2, but not anti-SC2P3, antisera contained antibodies against the conformational epitope(s) in the SC2 molecule. However, SC2P3 or SC2P5 immunization plus anti-SC2 antibody transfer aggravated the disease only slightly. These findings suggest that C-protein-induced EAM is formed by activation of C-protein-specific T cells along with antibodies against conformational epitopes in C-protein but that there are undetermined factors related to the disease progression. Further analysis of C-protein-induced EAM will provide useful information to elucidate the pathomechanisms of human polymyositis.
Matsumoto
Yoh
Y
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo, Japan. matyoh@tmin.ac.jp
Kohyama
Kuniko
K
Park
Il-Kwon
IK
Nakajima
Mie
M
Hiraki
Keiko
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D017285:Polymyositis / Q000139:chemically induced / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D000099163:Myosin Binding Protein C
D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D002352:Carrier Proteins; D000939:Epitopes; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D000099163:Myosin Binding Protein C