An inhibitory monoclonal antibody to human acetylcholinesterases

The monoclonal antibody AE-2 raised against acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) from human erythrocytes is shown to inhibit the enzyme activity. The reaction of the antibody with a structural epitope is investigated further. The epitope resides on monomeric, dimeric and tetrameric species of the enzyme. The rate of phosphorylation of the enzyme by diisopropylfluorophosphate was not affected by the antibody. On the other hand, inhibitors directed towards the anionic site(s) competed with antibody binding, suggesting that one of these is the epitope. The titration with antibody is biphasic and yields about 80% inhibition even in the presence of a large excess of antibody. Inhibition is fully reversible upon dilution, in a time-dependent manner. AE-2 also inhibited human adult and fetal brain acetylcholinesterase (to the same extent). However bovine brain acetylcholinesterase was inhibited to a lesser extent and rat brain acetylcholinesterase did not interact with the antibody. Butyrylcholinesterase (EC 3.1.1.8) also showed no reactivity towards the antibody.