Antibodies from patients with myasthenia gravis recognize determinants unique to extrajunctional acetylcholine receptors.

We have examined the interaction between sera from patients with myasthenia gravis and acetylcholine receptor (AcChoR) purified from normal and denervated rat skeletal muscles [junctional receptor (JR) and extrajunctional receptor (EJR), respectively]. Eight of ten myasthenic sera had titers against EJR that were significantly higher (1.1-2.4 times) than their titers against JR. The antireceptor titers of these sera ranged from 2 to 102 nM. Although activities of three other sera were too low (less than 1 nM) to allow accurate titrations, provisional measurements with these sera gave titers against EJR that were at least as high (1.0-1.4 times) as those against JR. Competition experiments with myasthenic sera demonstrated two classes of determinants on rat AcChoR: those that are common to JR and EJR and those that are present or exposed only on EJR. Myasthenic sera did not recognize any determinants unique to JR. Several antisera raised to purified AcChoR from eel or Torpedo electric organs or denervated rat skeletal muscle had equal titers against the two forms of receptor. Treatment of JR and EJR by various enzymatic or chemical procedures designed to alter prosthetic groups on the proteins failed to affect their antigenic reactivity. AcChoR from embryonic rats was indistinguishable immunologically from EJR of adult muscle.