Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease.
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...
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doaj-20cc86a363084972a05f4aec70c7c3cd2020-11-25T01:27:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10283910.1371/journal.pone.0102839Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease.Anna VangoneSafwat Abdel-AzeimIvana CaputoDaniele SblatteroRoberto Di NiroLuigi CavalloRomina OlivaAnti-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.http://europepmc.org/articles/PMC4116137?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna Vangone Safwat Abdel-Azeim Ivana Caputo Daniele Sblattero Roberto Di Niro Luigi Cavallo Romina Oliva |
spellingShingle |
Anna Vangone Safwat Abdel-Azeim Ivana Caputo Daniele Sblattero Roberto Di Niro Luigi Cavallo Romina Oliva Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. PLoS ONE |
author_facet |
Anna Vangone Safwat Abdel-Azeim Ivana Caputo Daniele Sblattero Roberto Di Niro Luigi Cavallo Romina Oliva |
author_sort |
Anna Vangone |
title |
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
title_short |
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
title_full |
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
title_fullStr |
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
title_full_unstemmed |
Structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
title_sort |
structural basis for the recognition in an idiotype-anti-idiotype antibody complex related to celiac disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4116137?pdf=render |
work_keys_str_mv |
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