Epitope-dependent Functional Effects of Celiac Disease Autoantibodies on Transglutaminase 2.

ABSTRACT: Transglutaminase 2 (TG2) is a Ca²⁺-dependent cross-linking enzyme involved in the pathogenesis of CD. We have previously characterized a panel of anti-TG2 mAbs generated from gut plasma cells of celiac patients and identified four epitopes (epitopes 1-4) located in the N-terminal part of TG2. Binding of the mAbs induced allosteric changes in TG2. Thus, we aimed to determine whether these mAbs could influence enzymatic activity through modulation of TG2 susceptibility to oxidative inactivation and Ca²⁺ affinity. All tested epitope 1 mAbs, as well as 679-14-D04, which recognizes a previously uncharacterized epitope, prevented oxidative inactivation and increased Ca²⁺ sensitivity of TG2. We have identified crucial residues for binding of 679-14-D04 located wit

SUBMITTER: Hnida K 

PROVIDER: S-EPMC5207253 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature