IMMUNOCHEMICAL CHARACTERIZATION OF ANTIACETYLCHOLINESTERASE INHIBITORY MONOCLONAL-ANTIBODIES

Monoclonal antibodies (mAbs) were prepared against native or DFP-inhib ited Torpedo californica acetylcholinesterase and native or DFP-, MEPQ -, and soman-inhibited fetal bovine serum acetylcholinesterase. The cr oss reactivity of these antibodies with acetylcholinesterases from var ious species and their ability to inhibit catalytic activity were dete rmined. Eight antibodies were found to inhibit catalytic activity of e ither Torpedo or fetal bovine serum enzyme. In all cases the antibodie s bound to the native form of the enzymes and in some cases even to th e denatured form. None of the antibodies recognized human or horse ser um butyrylcholinesterase. Sucrose density gradient centrifugation of e nzyme-antibody complexes provided two types of profiles, one with mult iple peaks, indicating numerous complexes between tetrameric forms of the enzyme, and the other with single peaks, demonstrating complex for mation within the tetrameric form. Different antibodies appeared to in teract with slightly different regions, but in all cases the binding e ncompassed the peripheral anionic site. Decrease in catalytic activity of the enzyme was most likely caused by conformational changes in the enzyme molecule resulting from interaction with these mAbs.