Immunogenic gluten peptides

Immunogenic gluten peptides are protein fragments resulting from the partial digestion of gluten proteins, primarily gliadins and glutenins, found in wheat, barley, and rye (Schuppan et al., 2009). These peptides are characterized by a high content of proline and glutamine residues, which renders them highly resistant to proteolysis by human gastric, pancreatic, and intestinal brush-border enzymes (Shan et al., 2002). In individuals with Celiac disease, these stable peptides cross the intestinal epithelial barrier and undergo deamidation by the enzyme tissue transglutaminase 2 (TG2) (Sollid, 2002). This modification significantly enhances their binding affinity to HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells, subsequently triggering a robust T-cell mediated inflammatory response and intestinal mucosal damage (Maki et al., 2003). Therapeutic approaches targeting these peptides include oral enzyme replacement therapies (glutenases) like Latiglutenase, designed to degrade them into non-toxic fragments before they reach the small intestine (Syage et al., 2017), as well as novel immunotherapies like TAK-101 aimed at restoring immune tolerance (Courtenay et al., 2020).

Other names

Gliadin peptidesGluten-derived peptides33-mer gliadin peptideProline-rich gluten peptidesAlpha-gliadin peptides

Therapeutic strategies involve the enzymatic degradation of these peptides in the stomach (glutenases), sequestration to prevent absorption, or the induction of immune tolerance through nanoparticle-mediated delivery or peptide-based immunotherapy (Sollid & Khosla, 2011; Syage et al., 2017).