Toxic, Immunostimulatory and Antagonist Gluten Peptides in Celiac Disease

Marco      Silano; Olimpia      Vincentini; Massimo      De Vincenzi

Abstract

Celiac disease (CD) is an increasingly diagnosed, permanent autoimmune enteropathy, triggered, in susceptible individuals, by the ingestion of gluten, the alcohol – soluble protein fraction of some cereals, such as wheat, rye and barley. The main protein of wheat gluten is called gliadin, the similar proteins of rye and barley are secalin and hordein, respectively. Approximately 96% of CD patients express the HLA molecule DQ2, while the remainder mostly express the less common haplotype DQ8, reflecting the pivotal role of these molecules in the pathogenesis of CD. Because of their aminoacid sequence and tri-dimensional structure, gluten peptides selectively bind to these HLA alleles present on the surface of antigen presenting cells and then they are presented to the T lymphocytes in intestinal mucosa, thus starting the inflammatory immune response. CD is defined by the characteristic histological changes of small bowel mucosa: villous atrophy, crypts hyperplasia and T cells infiltration of the lamina propria, along with the increase of the number of intraepithelial lymphocytes. The withdrawal of the gluten- containing food from the diet determines a complete recovery of the intestinal mucosa, whereas the reintroduction causes a relapse of the disease. This review focuses on the description of gluten peptides that elicit the mucosal immune response via the activation of innate and adaptive immunity in CD. It also describes the antagonist gluten peptides, obtained by artificial modification of gluten T epitopes or naturally occurring in the alcohol protein fraction of a cultivar of durum wheat, able to immunomodulate the pathogenic immune response of CD.

Keywords: Celiac disease, gluten, tissue transglutaminase, T-cells epitopes, DQ binding, mucosal inflammation

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