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 to xic to coeliac small bowel, Analogues of this peptide, which bind to DQ2 mo lecules but are non-toxic, may be a potential route to inducing tolerance t o gliadin in patients with coeliac disease. Methods: Toxicity was investigated with small bowel organ culture in six pa tients with untreated coeliac disease, four with treated coeliac disease an d 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. Peptid es 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 init ial step towards investigation of the induction of tolerance to gliadin in patients affected by coeliac disease.