Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells.

ABSTRACT: The gluten-sensitive enteropathy celiac disease is tightly associated with the production of autoantibodies specific for the enzyme transglutaminase 2 (TG2). The mechanisms underlying the activation of autoreactive B cells, however, are not well defined. To gain more insight into this autoimmune response we have characterized the binding of TG2 by a panel of human mAbs generated by expression cloning of Ig genes from single plasma cells of the celiac disease lesion. The Abs were highly specific to TG2 and bound preferentially to the open, Ca(2+)-activated enzyme conformation. Epitope mapping revealed that they recognize few distinct conformational epitopes that cluster in the N-terminal half of the enzyme. Two of the epitopes were overlapping with the fibronectin binding site in TG2, and n

SUBMITTER: Iversen R 

PROVIDER: S-EPMC3728568 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature