Monoclonal anti-acetylcholine-receptor antibodies directed against the cholinergic binding site.

We have isolated 32 hybridoma cell lines producing monoclonal antibodies against the acetylcholine receptor from Torpedo californica. One of these lines, designated 5.5.G.12, secretes antibodies which are directed against the cholinergic binding site of the acetylcholine receptor. This specific antibody blocked the binding of alpha-bungarotoxin to the acetylcholine receptor. The binding of monoclonal antibody 5.5.G.12 to acetylcholine receptor was inhibited by alpha-neurotoxins and by other cholinergic ligands in accordance with their affinities to the nicotinic acetylcholine receptor. None of the other monoclonal antibodies obtained inhibited the binding of alpha-bungarotoxin to acetylcholine receptor, nor was their binding to the acetylcholine receptor inhibited by cholinergic ligands. The monoclonal antibody elicited against the binding site of Torpedo acetylcholine receptor bound also to acetylcholine receptors of various species and organs, demonstrating the wide structural homology between the cholinergic sites of various acetylcholine receptors.