Deamidation of gliadin peptides in lamina propria: implications for celiac disease. 2008

H Skovbjerg, and D Anthonsen, and E Knudsen, and H Sjöström
Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark. hsk@imbg.ku.dk

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.

UI MeSH Term Description Entries
D009092 Mucous Membrane An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa. Lamina Propria,Mucosa,Mucosal Tissue,Muscularis Mucosae,Mucous Membranes,Membrane, Mucous,Membranes, Mucous,Mucosae, Muscularis,Mucosal Tissues,Propria, Lamina,Tissue, Mucosal,Tissues, Mucosal
D010047 Ovalbumin An albumin obtained from the white of eggs. It is a member of the serpin superfamily. Serpin B14
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011503 Transglutaminases Transglutaminases catalyze cross-linking of proteins at a GLUTAMINE in one chain with LYSINE in another chain. They include keratinocyte transglutaminase (TGM1 or TGK), tissue transglutaminase (TGM2 or TGC), plasma transglutaminase involved with coagulation (FACTOR XIII and FACTOR XIIIa), hair follicle transglutaminase, and prostate transglutaminase. Although structures differ, they share an active site (YGQCW) and strict CALCIUM dependence. Glutaminyl-Peptide Gamma-Glutamyltransferases,Protein-Glutamine gamma-Glutamyltransferases,Transglutaminase,Gamma-Glutamyltransferases, Glutaminyl-Peptide,Glutaminyl Peptide Gamma Glutamyltransferases,Protein Glutamine gamma Glutamyltransferases,gamma-Glutamyltransferases, Protein-Glutamine
D002446 Celiac Disease A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION. Gluten Enteropathy,Sprue, Celiac,Sprue, Nontropical,Celiac Sprue,Gluten-Sensitive Enteropathy,Sprue,Disease, Celiac,Enteropathies, Gluten,Enteropathies, Gluten-Sensitive,Enteropathy, Gluten,Enteropathy, Gluten-Sensitive,Gluten Enteropathies,Gluten Sensitive Enteropathy,Gluten-Sensitive Enteropathies,Nontropical Sprue
D003641 Deamination The removal of an amino group (NH2) from a chemical compound. Deaminations
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004386 Duodenum The shortest and widest portion of the SMALL INTESTINE adjacent to the PYLORUS of the STOMACH. It is named for having the length equal to about the width of 12 fingers. Duodenums
D005903 Gliadin Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with CELIAC DISEASE. alpha-Gliadin,alpha Gliadin
D005983 Glutens Prolamins in the endosperm of SEEDS from the Triticeae tribe which includes species of WHEAT; BARLEY; and RYE. Gluten,Gluten Protein,Glutelin,Glutelins,Gluten Proteins,Hordein,Hordeins,Secalin,Secalins,Protein, Gluten

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