| Project/Area Number |
63480215
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Kanazawa University |
|---|
Principal Investigator |
TAKAMORI Masaharu Kanazawa University Hospital ; Department of Neurology ; Professor, 医学部・附属病院・神経内科, 教授 (60039815)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Seiichi Kanazawa University Hospital ; Department of Neurology ; Instructor, 医学部・附属病院・神経内科, 助手 (60152435)
IDE Yoshihiko Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院・神経内科, 講師 (10100835)
MATSUBARA Shiro Kanazawa University Hospital ; Department of Neurology ; Assistant Professor, 医学部・附属病院・神経内科, 講師 (00143884)
|
|---|
| Project Period (FY) |
1988 – 1990
|
| Project Status |
Completed (Fiscal Year 1990)
|
| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | Myasthenia Gravis / Acetylcholine Receptor / Synthetic Peptides / Receptor Molecular Structure / Immune Cells / Antibody / Animal Model / B細胞認識 / T細胞認識 / 抗アセチルコリン受容体抗体 / T細胞 / B細胞 |
|---|
| Research Abstract |
Upon the availability of amino acid sequences and transmembrane topography of acetylcholine receptor (AChR) alpha-subunit, the research attempted to localize myasthenic domains on AChR, such as the sites recognized by the "blocking antibody" which prevents the binding of ACh with AChR and by the "binding antibody" which accelerates the degradation of AChR, by use of peptides synthesized referring to AChR molecular structure, resulting in the following : (1) The synthetic peptide, alpha183-200, was immunogenic in the induction of myasthenia in animals and antigenic in the detection of antibody in human myasthenic patients. (2) Myasthenic patients treated with plasmaperfusion by use of the synthetic peptide (alpha183-200)-bound adsorbent showed clinical improvement in association with the reduction of corresponding anti-peptide antibody and anti-native AChR blocking antibody in sera.
(3) Synthetic peptides, alpha67-76, alpha70-90 and alpha125-147, were stimulatory to the induction of myasthenia in animals, and were useful to detect myasthenic antibody in humman myasthenic sera. (4) Nineteen segments in the molecular structure of ACha alpha-subunit were found to be T-cell epitopes, but they were not potent to stimulate B-cells. (5) Artificially formed peptides were synthesized by coupling natural AchR peptides and theoretical amino acid sequences based on the concept that the induction of myasthenia gravis depends on linked recognition of the B-cell epitope expected at beta-turn structure and the T-cell epitope expected at amphipathic alpha-helical structure.
These conformationally modified AChR peptides were more immunogenic and antigenic than AChR peptides of natural sequences, and provided a provision for the antigenspecific therapy in myasthenia qravis.
|
