Myasthenogenic significance of synthetic alpha-subunit peptide 183-200 of Torpedo californica and human acetylcholine receptor.
Synthetic peptides of the Torpedo californica and human acetylcholine receptor alpha-subunit, Gly183-Asp200, were studied. Both peptides bound alpha-bungarotoxin to a significant extent, and inhibited toxin-binding with Torpedo or human acetylcholine receptor. The human peptide was, however, less potent than the Torpedo peptide. One can assume, therefore, that this sequence participates in cholinergic binding. The Torpedo alpha 183-200 segment was immunogenic in the induction of experimental autoimmune myasthenia gravis in rats, accompanied by elevation of anti-peptide and anti-rat acetylcholine receptor blocking antibody and reduced amplitudes of miniature end-plate potentials. Sera did not accelerate the degradation of rat acetylcholine receptor. Thus, one may interpret this to be the animal model induced by an immunopharmacological blockade of the acetylcholine-binding site. Furthermore, this Torpedo peptide was antigenic in the detection of antibody in human myasthenic sera. The human alpha 183-200 segment had neither of these 2 properties, although the corresponding anti-peptide antibody was elicited in immunized rats. It is feasible that the synthetic segment of this human sequence may not be maintained in such a conformation to be immunogenic.
Takamori
M
M
Department of Neurology, Kanazawa University School of Medicine, Japan.
Okumura
S
S
Nagata
M
M
Yoshikawa
H
H
D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism; D005260:Female; D006801:Humans; D009157:Myasthenia Gravis / Q000139:chemically induced* / Q000276:immunology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000138:chemical synthesis / Q000276:immunology*; D014101:Torpedo / Q000378:metabolism*
D001323:Autoantibodies; D002038:Bungarotoxins; D010446:Peptide Fragments; D011950:Receptors, Cholinergic