MIMICRY BETWEEN RECEPTORS AND ANTIBODIES - IDENTIFICATION OF SNAKE TOXIN DETERMINANTS RECOGNIZED BY THE ACETYLCHOLINE-RECEPTOR AND AN ACETYLCHOLINE RECEPTOR-MIMICKING MONOCLONAL-ANTIBODY

In several instances, a monoclonal antibody raised against a receptor ligand has been claimed to mimic the ligand receptor, Thus, a specific monoclonal antibody (M alpha 2-3) raised against a short chain toxin from snake was proposed to mimic the nicotinic acetylcholine receptor (AChR) (1), Further confirming this mimicry, we show that (i) like ACh R, M alpha 2-3 elicits anti-AChR antibodies, which in turn elicit anti -toxin antibodies; and (ii) the region 106-122 of the alpha-chain of A ChR shares 66% primary structure identity with complementarity-determi ning regions of M alpha 2-3. Also, a mutational analysis of erabutoxin a reveals that the epitope recognized by M alpha 2-3 consists of 10 r esidues, distributed within the three toxin loops, Eight of these resi dues also belong to the 10-residue epitope recognized by AChR, a resul t that offers an explanation as to the functional similarities between the receptor and the antibody, Strikingly, however, most of the resid ues common to the two epitopes contribute differentially to the energe tic formation of the antibody-toxin and the receptor-toxin complexes, Together, the data suggest that the mimicry between AChR and M alpha 2 -3 is partial only.