| Project/Area Number |
03454239
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKAMORI Masaharu Kanazawa University School of Medicine ; Department of Neurology ; Professor, 医学部, 教授 (60039815)
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| Co-Investigator(Kenkyū-buntansha) |
NITTA Eishun Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 助手 (50251947)
SAKATO Shunichi Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 助手 (10142275)
IDE Yoshihiko Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院, 講師 (10100835)
奥村 誠一 金沢大学, 医学部附属病院, 助手 (60152435)
松原 四郎 金沢大学, 医学部, 講師 (00143884)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1992: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Acetylcholine receptor / Synthetic peptides / Antibody / Immune cells / Myasthenia gravis / 血液浄化療法 / 抗体 / 免疫原 / 疾患モデル動物 |
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| Research Abstract |
Myasthenogenic regions in the acetylcholine receptor (AChR)alpha-subunit were studied in view of the conformation-dependent B-cell epitope expected at beta-turn and the MHC class II-restricted T-cell epitope expected at alpha-helix. Torpedo AChR alpha67-76 and alpha107-116 were synthesized as the main immunogenic region and the site specific for T-cell epitope in Lewis rat, respectively. Model peptides, synthesized by combining these natural sequence segments or by intervening the segment aligned as NPGG in natural sequence segments, were tested in terms of antigenic conformation. The model peptide, alpha107-116.alpha67-76.alpha107-116, was potently immunogenic in the induction of the animal model of myasthenia, accomplanied by the anti-peptide antibody cross-reactive with the native AChR.High antigenicity in antibody assays for vaious peptide- and native AChR-immunized rats was found when the model peptides, alpha107-116.alpha67-76 and/or alpha107-116. NPGG.aplha67-76, were used for measurement as antigens. Since none of these model peptides was reactive with antibody in human myasthenics, peptides were therefore designed to conforom to the antigen appropriate for binding with human myasthenic antibody. As the result, 4 model peptides, CKGGLR.alpha67-76.C,KKC.alpha63-77.C, KKC.alpha62-77, and KKCalpha 61-77-C, were potently reactive with monoclonal myasthenic antibody and useful for detecting antibody in human myasthenics.
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