[Biochemical approaches to neuromuscular junction disorders]

In view of the conformation-dependent B-cell epitope and the MHC class II-restricted T-cell epitope, myasthenogenic sites in the molecular structure of acetylcholine receptor alpha-subunit were defined by the induction of a rat model of myasthenia gravis using synthetic peptides, alpha 183-200, alpha 125-147 and alpha 67-76 with alpha 107-116. Structural model for the acetylcholine receptor synthetic peptides were designed to obtain a conformation that was highly antigenic compared with that of natural sequence peptides. To search for antigenic sites in the molecular structure of P/Q type of voltage-gated calcium channel (alpha 1) in Lambert-Eaton myasthenic syndrome (LEMS), LEMS patients' sera were studied by immunoprecipitation assay using antigens synthesized referring to its sequential residue map. Peptides corresponding to extracellular region (S5 S6 linker) of domains II and IV were specifically reactive with LEMS antibodies; their titers respectively correlated with those of anti-P/Q type calcium channel (human cerebellum). The extracellular region of synaptotagmin, a synaptic vesicle protein that acts as a calcium sensor in release of acetylcholine, was also immunogenic in the induction of a rat model of LEMS; a proportion of LEMS patients' sera reacted with recombinant synaptotagmin in immunoblot.