Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease
Di Niro, Roberto
KAUST DepartmentKAUST Catalysis Center (KCC)
MetadataShow full item record
AbstractAnti-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. © 2014 Vangone et al.
CitationVangone A, Abdel-Azeim S, Caputo I, Sblattero D, Di Niro R, et al. (2014) Structural Basis for the Recognition in an Idiotype-Anti-Idiotype Antibody Complex Related to Celiac Disease. PLoS ONE 9: e102839. doi:10.1371/journal.pone.0102839.
PublisherPublic Library of Science (PLoS)
PubMed Central IDPMC4116137
Except where otherwise noted, this item's license is described as This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Structural Basis for Antigen Recognition by Transglutaminase 2-specific Autoantibodies in Celiac Disease.
- Authors: Chen X, Hnida K, Graewert MA, Andersen JT, Iversen R, Tuukkanen A, Svergun D, Sollid LM
- Issue date: 2015 Aug 28
- Anti-idiotypic response in mice expressing human autoantibodies.
- Authors: Di Niro R, Sblattero D, Florian F, Stebel M, Zentilin L, Giacca M, Villanacci V, Galletti A, Not T, Ventura A, Marzari R
- Issue date: 2008 Mar
- A single conformational transglutaminase 2 epitope contributed by three domains is critical for celiac antibody binding and effects.
- Authors: Simon-Vecsei Z, Király R, Bagossi P, Tóth B, Dahlbom I, Caja S, Csosz É, Lindfors K, Sblattero D, Nemes É, Mäki M, Fésüs L, Korponay-Szabó IR
- Issue date: 2012 Jan 10
- Autoantibodies and CD: past and future of celiac antibody testing.
- Authors: Korponay-Szabó IR
- Issue date: 2014 Jul
- Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange.
- Authors: Iversen R, Mysling S, Hnida K, Jørgensen TJ, Sollid LM
- Issue date: 2014 Dec 2