Epitopes described in "Wheat peptide challenge in coeliac disease."

Article Authors:R Sturgess; P Day; H J Ellis; K E Lundin; H A Gjertsen; M Kontakou; P J Ciclitira
Article Title:Wheat peptide challenge in coeliac disease.
Reference Detail
Reference ID:1005306
Abstract:The exact nature of the cereal moiety that exacerbates coeliac disease is unknown. In-vitro studies have implicated both the N-terminal and far C-terminal domains of one of the wheat prolamins, A-gliadin. Peptides within these regions may act as epitopes that trigger immune events leading to enteropathy. We synthesized three peptides corresponding to amino-acids 3-21, 31-49, and 202-220 of A-gliadin. Four patients with coeliac disease were challenged by intraduodenal infusion of 1 g of gliadin or 200 mg of the synthetic peptides. Jejunal biopsies were taken before and at hourly intervals for 6 h after the infusion. Morphometric variables were measured and intraepithelial lymphocytes counted. Significant histological changes occurred in the small intestinal mucosa after challenge with a synthetic peptide corresponding to amino acids 31-49 of A-gliadin. The N-terminal peptide, residues 3-21 of A-gliadin, did not cause histological changes in any of the patients. In one of the four patients, minor histological changes following challenge with the peptide corresponding to residues 202-220 of A-gliadin were seen. Our results suggest that the oligopeptide corresponding to aminoacids 31-49 of A-gliadin is toxic in vivo, but there is no evidence of toxicity of the far N-terminal peptide, residues 3-21. The C-terminal peptide 202-220 may contain an epitope to which patients with coeliac disease display variable sensitivity. Since the oligopeptide corresponding to amino-acids 31-49 of A-gliadin is recognised by HLA DQ2-restricted T cells, the observed effects may be due to immune activation within the intestinal mucosa.
Affiliations:Rayne Institute Division of Pharmacology, St Thomas' Hospital, London, UK.
Reference Type:Literature
PubMed ID:7907731
Journal Volume:343
Article Pages:758-61
Journal ISSN:0140-6736
Article Chemical List:Allergens;Antigens, CD3;Peptides;Gliadin
Article MeSH List:Adult; Aged; Allergens; Amino Acid Sequence; Antigens, CD3(immunology ); Celiac Disease(immunology ); Female; Gliadin(chemical synthesis; immunology ); Humans; Intestinal Mucosa(immunology; pathology ); Intestine, Small(immunology; pathology ); Leukocyte Count; Male; Middle Aged; Molecular Sequence Data; Peptides(chemical synthesis; immunology ); Triticum
Curation Last Updated:2014-10-03 20:39:46