Enzymatic Strategies to Detoxify Gluten: Implications for Celiac Disease

Figure 1

Tissue transglutaminase (tTG)-mediated post-translational modifications in celiac disease. Gliadin peptides reach the subepithelial region of the intestinal mucosa. Here, tTG deamidation of specific glutamines of gliadin peptides generates potent immunostimulatory epitopes that are presented via HLA-DQ2/DQ8 on antigen-presenting cells (APC) to CD4⁺ T cells. Activated gliadin-specific CD4⁺ T cells produce high levels of pro-inflammatory cytokines, thus inducing a Th₁ response that results in mucosal remodelling and villous atrophy. In addition, tTG transamidation activity generates tTG-gliadin complexes that bind to tTG-specific B cells, are endocytosed and processed. Gliadin-DQ2/DQ8 complexes are then presented by the tTG-specific B cells to gliadin-specific T cells, a process that leads to the production of anti-tTG antibodies.