| Project/Area Number |
12670637
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Tokyo Metropolitan Institute for Neuroscience |
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Principal Investigator |
KOHYAMA Kuniko Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所, 研究員 (80301795)
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| Co-Investigator(Kenkyū-buntansha) |
TANUMA Naoyuki Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所, 研究員 (00281676)
MATSUBARA Shiro Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所, 研究員 (00143884)
MATSUMOTO Yoh Tokyo Metropolitan Inst. for Neurosci., 東京都神経科学総合研究所, 参事研究員 (90173921)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | polymositis / myositogenic antigen / T cell receptor / C-protein |
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| Research Abstract |
To obtain a good animal model for polymyositis, we previously induced experimental autoimmune myositis (EAM) in Lewis rats by immunization with partially purified skeletal myosin. However, the nature of EAM-inducing antigen (s) in the partially purified myosin preparation remains unclear because it may contain several myositogenic antigens. In the present study, we further purified myosin and C-protein from partially purified myosin preparations and examined their EAM-inducing ability. It was revealed that immunization with both C-protein and purified myosin elicited EAM, which was essentially the same as that induced by partially purified myosin. However, their myositogenic ability was quite different. C-protein induced severe EAM of high histological grade and lesion frequency, whereas purified myosin induced only mild EAM. Immunohistochemical staining of C-protein-induced lesions demonstrated that muscle fiber-infiltrating cells were CD8+ T cells and macrophages and that CD4+ cells were mainly located in the endomysium and interfiber connective tissue. Collectively, these findings suggest that C-protein in the skeletal muscle is the major myositogenic antigen and induces inflammatory lesions mimicking those of human polymyositis.
In this project, we further analyzed the precise antigen speacificity of myositis-inducing T cells using recombinant C-protein fragments 1-4 and synthetic peptide. Immunization with Fragment 1-4 induced EAM more or less in Lewis rats but Fragment 2 showed the most potent myositogenicity. T cells isolated from rats that had been immunized with Fragment 2 responded vigorously to the mixture of synthetic peptides 4-6, suggesting that the major T cell epitope resides within C-protein residue 76-153.More precise analysis will provide useful information for the development of immunospecific gene therapy.
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