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Novel mechanisms of gliadin immunotoxicity?
  1. Eduardo Arranz1,
  2. Jose A Garrote1,2
  1. 1Mucosal Immunology Lab, Instituto de Biologia y Genetica Molecular (IBGM), University of Valladolid-CSIC, Valladolid, Spain
  2. 2Research Unit, Hospital Clínico Universitario (IECSCYL), Valladolid, Spain
  1. Correspondence to Dr Eduardo Arranz, Mucosal Immunology Lab, Dept of Paediatrics & Immunology-IBGM, University of Valladolid, Spain. C/ Ramón y Cajal, 7. 47005, Valladolid, Spain; earranz{at}med.uva.es

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Coeliac disease (CoD) is a chronic inflammatory intestinal disorder caused by dietary gluten proteins (prolamines) from cereals in genetically predisposed individuals. The disease is manifested by a lesion which ranges from a complete transformation of the mucosa with villus atrophy and crypt cell hyperplasia to the infiltration by lymphocytes of the epithelium and lamina propria. Gluten is uniquely resistant to gastrointestinal digestion, and gluten fragments accumulate in the intestine where they trigger two distinct immune responses, mediated by the innate and adaptive immunity, and both contribute to the pathogenesis of CoD.1 2 Although HLA-DQ2/8 is the major predisposing factor, other non-HLA genes, some of them related to the innate response,3 and/or environmental factors might contribute to the development of the disease in a small group of DQ2+ individuals.

Immunostimulatory peptides, as assessed by using lymphocyte-based systems, have been identified in gliadin and glutenins from wheat gluten, and homologues from barley and rye. All peptides which are stimulatory when tested in vitro are also harmful in vivo. The best known is the immunogenic peptide p57-89 (33mer) from α-gliadin, which is the preferred substrate for tissue transglutaminase (TGt) and once deaminated becomes a potent activator of gluten-specific DQ2-restricted CD4+ T cells from patients with CoD, characterised by interferon γ (IFNγ) production. Other peptides, …

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