| Project/Area Number |
10470154
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
KIRA Jun-ichi Kyushu University, Medical Science, Professor, 大学院・医学系研究科, 教授 (40183305)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Taiji Kumamoto University, Medical Science, Professor, 大学院・医学研究科, 教授 (10156119)
WATANABE Takeshi Kyushu University, Medical Science, Professor, 生体防御医学研究所, 教授 (40028684)
原 英夫 九州大学, 医学部, 講師 (00260381)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥9,500,000 (Direct Cost: ¥9,500,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | multiple sclerosis / opticospinal / myelin protein / autoreactive T cell / HLA-class II / epitope spreading / HLA / 髄鞘 / T細胞 / Myelin basic protein / Proteolipid protein / Myelin oligodendrocyte glycoprotein / 脊髄 |
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| Research Abstract |
In Japanese, we previously reported the existence of two subtypes of multiple sclerosis (MS), namely, Asian type MS, in which the clinically estimated lesions are confined to the optic nerves and spinal cord, and Western type MS showing disseminated lesions in the CNS including the cerebrum, cerebellum and brainstem. In the present study, sixty-four myelin overlapping peptides consisting of 16-21 residues which correspond to the human MBP, PLP and MOG sequences were synthesized and myelin peptide specific autoreactive CD4+T cell lines were established by stimulating PBMC with these peptides from MS patients and healthy controls. MS patients tended to show epitope spreading in autoreactive CD4+T cell lines as compared with healthy controls. Reactivity against the mixture of overlapping peptides derived from each myelin proteins was then determined. The results indicated that reactivity to MOG was predominant as Asian type MS. On the other hand, Western type MS showed response to all mye
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lin proteins examined. It has been previously reported that the lesions were confined to the optic nerves and spinal cord in BN rats sensitized with MOG. These findings may indicate that predominant reactivity to MOG in Asian type MS may contribute to the development of opticospinal from MS. Furthermore, DP5(DPA1ィイD1*ィエD102022/DPBAィイD1*ィエD10501) restricted autoreactive CD4+T cell clone (SS1. 2) was established in Asian type MS. SS1.2 recognized 196MBP peptide p74-93 and 170MPB peptide p47-67 and responded to the recombinant 170MBP protein. We investigated responses of SS1.2 to analog peptides with single amino acid substitution. It was found that residues 84 (position 1(p1)), 86(p3), 87(p4), 89(p6) and 90(p7) of the peptide were critical for its binding to DP5 molecule and recognition by TCR. On the basis of these observations, we are going to establish an expression library system for searching peptides recognized by the autoreactive CD4+T cells from DP5 positive Asian type MS patients, we expect that specific antigens in Asian type MS could be explored by such a system in future, Less
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