Multiple forms of anti-acetylcholine receptor antibody in myasthenia gravis

Sera of patients with myasthenia gravis (MG) contain anti-acetylcholine receptor (AChR) IgG antibodies (Ab) which have different antigenic specificities. Three Ab types were detected: (1) MG-I, which forms immune complexes with AChR; (2) MG-C, which decreases binding of AChR to concanavalin A; and MG-B, which blocks alpha-bungarotoxin binding to AChR. Sera from 152 MG patients were screened for the Ab types. Sixty-one percent contained MG-I, 26% contained MG-C, 10% contained MG-B, and 5% contained both MG-C and MG-B. The latter Ab types were associated with more severe forms of MG but showed no other clinical correlations. IgG antibodies of defined type were purified, and their interaction with unlabeled and toxin-prelabeled AChR from denervated rat muscle was studied in detail. Receptors are homogeneous with respect to determinants recognized by MG-I, but heterogeneous with respect to determinants recognized by MG-C (3 subpopulations, 22%, 28%, and 50% of AChR) and by MG-B (2 subpopulations, 30% and 70% of AChR). The stoichiometry of AChR interaction with the antibodies indicates that for each toxin-binding site, the receptor is divalent as an antigen for MG-I and MG-C but is tetravalent for MG-B. Denervated muscle AChR appears to be a mixture of at least 3 molecular forms of AChR, each of which has distinct immunological features as well as components common to all the receptor subpopulations.