Wheat peptide challenge in coeliac disease

Lancet. 1994 Mar 26;343(8900):758-61. doi: 10.1016/s0140-6736(94)91837-6.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allergens
  • Amino Acid Sequence
  • CD3 Complex / immunology
  • Celiac Disease / immunology*
  • Female
  • Gliadin / chemical synthesis
  • Gliadin / immunology*
  • Humans
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Intestine, Small / immunology
  • Intestine, Small / pathology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Triticum*


  • Allergens
  • CD3 Complex
  • Peptides
  • Gliadin