cobrotoxin and Autoimmune-Diseases

Topics: Acetylcholine; Animals; Autoimmune Diseases; Cobra Neurotoxin Proteins; Disease Models, Animal; Humans; Membrane Potentials; Motor Endplate; Myasthenia Gravis; Rats; Receptors, Cholinergic; Synaptic Transmission

Serotherapy, an approach currently used to protect humans against animal bites or stings, is often too specific. To broaden antiserum paraspecificity, use of antibodies directed against areas shared by all members of a toxin family was previously proposed. MST2 is a mAb that recognizes all long-chain curaremimetic toxins (Charpentier et al. (1990) J. Mol. Recog. 3, 74-81). It binds to toxin residues that make contact with the toxin's target, e.g., the nicotinic acetylcholine receptor (AcChoR). We now show that MST2 also recognizes (-) nicotine, an agonist of AcChoR. Binding properties of MST2 therefore mimick, at least partially, binding properties of AcChoR. Injection in rabbits of MST2 mixed with adjuvant, elicited anti-idiotypic (anti-Id) antibodies that inhibited binding of the toxin to AcChoR. A proportion of these anti-Id antibodies specifically bound AcChoR and thereby mimicked the toxin. Furthermore, rabbits immunized with MST2 elicited auto-anti-anti-Id antibodies capable of binding the toxin. Our data provide a molecular explanation for the previously reported signs of myasthenia gravis as triggered by antibodies raised against cholinergic antagonists. Implications in the design of antisera to toxic proteins are discussed.

Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Autoimmune Diseases; Binding Sites; Cobra Neurotoxin Proteins; Immunization; Myasthenia Gravis; Neuromuscular Nondepolarizing Agents; Nicotine; Protein Conformation; Rabbits; Receptors, Cholinergic