title: Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease.
abstract: Anti-idiotype antibodies have potential therapeutic applications in many fields, including autoimmune diseases. Herein we report the isolation and characterization of AIM2, an anti-idiotype antibody elicited in a mouse model upon expression of the celiac disease-specific autoantibody MB2.8 (directed against the main disease autoantigen type 2 transglutaminase, TG2). To characterize the interaction between the two antibodies, a 3D model of the MB2.8-AIM2 complex has been obtained by molecular docking. Analysis and selection of the different obtained docking solutions was based on the conservation within them of the inter-residue contacts. The selected model is very well representative of the different solutions found and its stability is confirmed by molecular dynamics simulations. Furthermore, the binding mode it adopts is very similar to that observed in most of the experimental structures available for idiotype-anti-idiotype antibody complexes. In the obtained model, AIM2 is directed against the MB2.8 CDR region, especially on its variable light chain. This makes the concurrent formation of the MB2.8-AIM2 complex and of the MB2.8-TG2 complex incompatible, thus explaining the experimentally observed inhibitory effect on the MB2.8 binding to TG2.
authors: Department of Chemistry and Biology, University of Salerno, Fisciano, Salerno, Italy.
authors: Anna
authors: A
authors: Vangone
authors: Kaust Catalysis Center, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors: Safwat
authors: S
authors: Abdel-Azeim
authors: Department of Chemistry and Biology, University of Salerno, Fisciano, Salerno, Italy; European Laboratory for the Investigation of Food-Induced Diseases (ELFID), University Federico II, Naples, Italy.
authors: Ivana
authors: I
authors: Caputo
authors: Department of Health Sciences and Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), University of Eastern Piedmont, Novara, Italy.
authors: Daniele
authors: D
authors: Sblattero
authors: Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors: Roberto
authors: R
authors: Di Niro
authors: Kaust Catalysis Center, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia; Department of Chemistry and Biology, University of Salerno, Fisciano, Salerno, Italy.
authors: Luigi
authors: L
authors: Cavallo
authors: Department of Sciences and Technologies, University "Parthenope" of Naples, Naples, Italy.
authors: Romina
authors: R
authors: Oliva
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry* / Q000378:metabolism; D001323:Autoantibodies / Q000737:chemistry / Q000378:metabolism; D001666:Binding Sites, Antibody; D002446:Celiac Disease / Q000276:immunology*; D019204:GTP-Binding Proteins / Q000276:immunology; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins