| 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.
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