title: Characterization of a monoclonal anti-idiotypic antibody that mimics cyclosporine A in a single binding system.
abstract: BALB/c mice were immunized with a mixture of two anti-cyclosporine (CsA) mAb, H4 1.3 and D3 1.3, which recognize CsA amino acid residues reported to be important for its biologic activity and for its interaction with a CsA-binding protein, cyclophilin. A syngeneic anti-Id mAb, P43E, an IgG1 kappa, was generated. P43E bound to F(ab)'2 fragments of H4 1.3 in an ELISA and showed a dose-dependent inhibition of CsA binding to H4 1.3 and D3 1.3 in ELISA and RIA. The anti-Id antibody could be purified on an affinity column of H4 1.3/D3 1.3, and its binding to H4 1.3 could be inhibited by CsA. Dissociation kinetics and Scatchard analyses of P43E binding to H4 1.3 supported a reciprocal competitive inhibition mechanism for anti-Id binding, excluding a steric hindrance mechanism. P43E did not bind to several other anti-CsA mAb, a rabbit polyclonal anti-CsA antibody preparation, or cyclophilin. It is, therefore, a mimic of CsA but restricted to a single binding system. Our results are in agreement with the epitope specificities of the antibodies, X-ray and electron microscopic analysis of idiotope-anti-idiotope interactions, and recent nuclear magnetic resonance spectrometry studies of a CsA-cyclophilin complex and have implications with respect to the bioeffective epitope of CsA.
authors.affiliation: Department of Microbiology, Columbia University, New York, NY 10032.
authors.forename: N A
authors.initials: NA
authors.lastname: Cacalano
authors.forename: W L
authors.initials: WL
authors.lastname: Cleveland
authors.forename: B F
authors.initials: BF
authors.lastname: Erlanger
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001667:Binding, Competitive; D016572:Cyclosporine / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D000939:Epitopes; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000939:Epitopes; D016572:Cyclosporine