PATHOGENESIS OF HYPERACUTE EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS - ACETYLCHOLINE RECEPTOR CHOLINERGIC SITE/RECEPTOR FUNCTION/AUTOIMMUNITY/

Three mAbs, mAbs 249E, 370, and 383C, directed against the alpha-bunga rotoxin (alpha BgTx) binding site of the acetylcholine receptor (AChR) induce a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), characterized by death within hours of mAb injection. To anal yze the mechanisms of this effect, purified AChR-mAb complexes were in vestigated for their ability to bind the cholinergic agonist carbamych oline and to undergo agonist-induced activation of the cholinergic ion ophore. The three mAbs inhibited carbamylcholine binding, and, convers ely, their binding to AChR was inhibited by carbamylcholine. All three completely inhibited carbamylcholine-induced T1(+) influxes to AChR-r ich vesicles. These data indicate that the severe hyperacute EAMG indu ced by these mAbs results from blockage of AChR function and that the role of such potent Abs (even ii present in small amounts) in the path ogenesis of human myasthenia gravis deserves further investigation.