Monoclonal antibodies to Torpedo acetylcholine receptor. Characterisation of antigenic determinants within the cholinergic binding site

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Abstract
Thirteen monoclonal antibodies (mAb) to the acetylcholine receptor (AChR) from T. marmorata showed high avidity for the receptor but none exhibited binding to muscle AChR solubilized from seven other animal species. Five mAb and Fab monomer fragments prepared from 2 of them, inhibited .alpha.-bungarotoxin (.alpha.BuTx) binding to receptor by a maximum of 50%. In the presence of excess mAb the 125I-.alpha.BuTx bound could be precipitated by anti-IgG indicating that the mAb bound to only 1 of the 2 .alpha.BuTx binding sites on each AChR monomer. This site appeared to have a lower affinity for d-tubocurarine and decamethonium than the non-mAb site. Binding of 5 anti-site mAb was mutually competitive and 4 of them (AS2-AS5) were inhibited by other cholinergic ligands and influenced by 4 non-toxin binding site antibodies. One (AS1) bound within the toxin binding site yet outside the main neurotransmitter binding region. Apparently these 5 mAb distinguish between the 2 .alpha.BuTx binding sites on the Torpedo AChR, and bind only to the site which displays lower affinity for d-tubocurarine and other competitive ligands.