title: Anti-idiotypic and anti-anti-idiotypic responses to a monoclonal antibody directed to the acetylcholine receptor binding site of curaremimetic toxins.
abstract: 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.
authors.affiliation: Département d'Ingenierie et d'Etudes des Protéines CE Saclay, Gif-sur-Yvette, France.
authors.forename: L
authors.initials: L
authors.lastname: Pillet
authors.forename: I
authors.initials: I
authors.lastname: Charpentier
authors.forename: M
authors.initials: M
authors.lastname: Léonetti
authors.forename: A
authors.initials: A
authors.lastname: Ménez
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000302:isolation & purification; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000276:immunology; D001665:Binding Sites; D003039:Cobra Neurotoxin Proteins / Q000276:immunology*; D007114:Immunization; D009157:Myasthenia Gravis / Q000276:immunology; D003473:Neuromuscular Nondepolarizing Agents / Q000276:immunology*; D009538:Nicotine / Q000276:immunology; D011487:Protein Conformation; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003039:Cobra Neurotoxin Proteins; D003473:Neuromuscular Nondepolarizing Agents; D011950:Receptors, Cholinergic; D009538:Nicotine