Epitopes described in "Structural basis for gluten intolerance in celiac sprue."

Article Authors:Lu Shan; √ėyvind Molberg; Isabelle Parrot; Felix Hausch; Ferda Filiz; Gary M Gray; Ludvig M Sollid; Chaitan Khosla
Article Title:Structural basis for gluten intolerance in celiac sprue.
Reference Detail
Reference ID:1005468
Abstract:Celiac Sprue, a widely prevalent autoimmune disease of the small intestine, is induced in genetically susceptible individuals by exposure to dietary gluten. A 33-mer peptide was identified that has several characteristics suggesting it is the primary initiator of the inflammatory response to gluten in Celiac Sprue patients. In vitro and in vivo studies in rats and humans demonstrated that it is stable toward breakdown by all gastric, pancreatic, and intestinal brush-border membrane proteases. The peptide reacted with tissue transglutaminase, the major autoantigen in Celiac Sprue, with substantially greater selectivity than known natural substrates of this extracellular enzyme. It was a potent inducer of gut-derived human T cell lines from 14 of 14 Celiac Sprue patients. Homologs of this peptide were found in all food grains that are toxic to Celiac Sprue patients but are absent from all nontoxic food grains. The peptide could be detoxified in in vitro and in vivo assays by exposure to a bacterial prolyl endopeptidase, suggesting a strategy for oral peptidase supplement therapy for Celiac Sprue.
Affiliations:Department of Chemical Engineering, Stanford University, Stanford, CA 94305-5025, USA.
Reference Type:Literature
PubMed ID:12351792
Journal Volume:297
Article Pages:2275-9
Journal ISSN:1095-9203
Article Chemical List:Epitopes, T-Lymphocyte;HLA-DQ Antigens;HLA-DQ2 antigen;Immunodominant Epitopes;Peptide Fragments;Recombinant Proteins;Gliadin;transglutaminase 2;Transglutaminases;Endopeptidases;Serine Endopeptidases;prolyl oligopeptidase;GTP-Binding Proteins
Article MeSH List:Amino Acid Sequence; Animals; Celiac Disease(immunology; therapy); Cell Line; Cereals(chemistry); Endopeptidases(metabolism); Epitopes, T-Lymphocyte; GTP-Binding Proteins(metabolism); Gliadin(chemistry; immunology; metabolism); HLA-DQ Antigens(immunology); Humans; Immunodominant Epitopes; Intestinal Mucosa(enzymology; immunology); Intestine, Small(enzymology; immunology); Lymphocyte Activation; Microvilli(enzymology); Molecular Sequence Data; Peptide Fragments(chemistry; immunology); Rats; Recombinant Proteins(chemistry; metabolism); Sequence Homology, Amino Acid; Serine Endopeptidases(administration & dosage; metabolism; therapeutic use); T-Lymphocytes(immunology); Transglutaminases(metabolism)
Curation Last Updated:2014-10-03 20:41:02