Deamidation of gliadin peptides in lamina propria: implications for celiac disease.
Activation of small intestinal gluten-reactive CD4(+) T-cells is a critical event in celiac disease. Deamidation of specific glutamine residues by tissue transglutaminase enhances the binding of T-cell activating gliadin epitopes to DQ2, increasing T-cell recognition. Our purpose was to investigate whether deamidated gliadin epitopes can be generated in the small intestinal mucosa by tissue transglutaminase and to characterize the location of the process. Intestinal explants from pig intestine and frozen biopsy slices from human and rat intestine were incubated with alpha-gliadin peptides containing the immunodominant motif. Monoclonal antibodies specifically recognizing the non-deamidated and/or the deamidated epitope were used for immunofluorescence studies. We conclude that endogenous tissue transglutaminase can mediate extracellular deamidation of gliadin peptides in the lamina propria. Gliadin peptides with more than one recognition site can be simultaneously cross-linked and deamidated extracellularly in the lamina propria, and might be of importance for the antibody response seen in untreated celiac disease patients.
Skovbjerg
H
H
Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark. hsk@imbg.ku.dk
Anthonsen
D
D
Knudsen
E
E
Sjöström
H
H
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001706:Biopsy; D002446:Celiac Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003641:Deamination; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D005903:Gliadin / Q000378:metabolism*; D005983:Glutens / Q000378:metabolism; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D010047:Ovalbumin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013552:Swine; D011503:Transglutaminases / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D010455:Peptides; D012710:Serum Albumin, Bovine; D005983:Glutens; D010047:Ovalbumin; D005903:Gliadin; D011503:Transglutaminases