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

Article Authors:Rasmus Iversen; Roberto Di Niro; Jorunn Stamnaes; Knut E A Lundin; Patrick C Wilson; Ludvig M Sollid
Article Title:Transglutaminase 2-specific autoantibodies in celiac disease target clustered, N-terminal epitopes not displayed on the surface of cells.
Reference Detail
Reference ID:1026317
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 none of the epitopes was accessible when TG2 was in a cell surface-bound form. Based on our findings, we propose that the autoantibodies are generated against the soluble, catalytically active enzyme, whereas Abs reactive with cell surface-associated TG2 are absent from the response due to negative selection of B cells recognizing membrane-bound self-Ag. The findings give insight into the mechanisms controlling the formation of anti-TG2 autoantibodies in celiac disease.
Affiliations:Centre for Immune Regulation, University of Oslo and Oslo University Hospital, N-0372 Oslo, Norway.
Reference Type:Literature
PubMed ID:23690478
Journal:J Immunol
Journal Volume:190
Article Pages:5981-91
Journal ISSN:0022-1767
Article Chemical List:Autoantibodies;Autoantigens;Epitopes, B-Lymphocyte;Transglutaminases;tissue transglutaminase 2, human
Article MeSH List:Animals; Antibody Specificity; Autoantibodies(immunology); Autoantigens(chemistry; immunology); Autoimmunity(immunology); Celiac Disease(immunology); Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes, B-Lymphocyte(chemistry; immunology); Flow Cytometry; Fluorescent Antibody Technique; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Transglutaminases(chemistry; immunology)
Curation Last Updated:2015-06-05 04:03:24