A non‐toxic analogue of a coeliac‐activating gliadin peptide: a basis for immunomodulation?

Background : A‐gliadin residues 31–49 (peptide A) binds to HLA‐DQ2 and is toxic to coeliac small bowel. Analogues of this peptide, which bind to DQ2 molecules but are non‐toxic, may be a potential route to inducing tolerance to gliadin in patients with coeliac disease. Methods : Toxicity was investigated with small bowel organ culture in six patients with untreated coeliac disease, four with treated coeliac disease and six controls. Analogue peptides comprised alanine substituted variants of peptide A at L31 (peptide D), P36 (E), P38 (F), P39 (G) and P42 (H). Results : Peptides D and E were toxic in biopsies from some patients. Peptides F, G and H were not toxic. Conclusions : Peptide F, which binds to DQ2 more strongly than peptide A, is not toxic in patients with coeliac disease in‐vitro ; this could be an initial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.