Gamma-gliadin immunogenic peptides

Gamma-gliadin immunogenic peptides are specific amino acid sequences derived from the partial proteolysis of gamma-gliadin, a major storage protein found in wheat gluten. These peptides are characterized by a high concentration of proline and glutamine residues, which makes them resistant to complete breakdown by human digestive enzymes in the stomach and small intestine (Sollid et al., 2012). In individuals with Celiac Disease, these persistent peptides cross the intestinal epithelium and are modified by the enzyme tissue transglutaminase 2, which deamidates glutamine residues into glutamate (Schuppan et al., 2009). This modification significantly increases the peptides' binding affinity for HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells, subsequently triggering an inflammatory T-cell response that leads to intestinal villous atrophy (Tye-Din et al., 2010). Therapeutic strategies targeting these peptides include the development of oral glutenases, such as Latiglutenase and TAK-062, which are designed to degrade the peptides into non-toxic fragments before they can trigger an immune response (Syage et al., 2017). Additionally, antigen-specific immunotherapies like Nexvax2 have been investigated to induce immune tolerance by exposing the immune system to these specific gamma-gliadin epitopes in a controlled manner (Goel et al., 2017).

Other names

γ-gliadinGamma-gliadinGluten-derived immunogenic peptidesCeliac-toxic peptides

Enzymatic degradation of immunogenic epitopes, induction of immune tolerance, and inhibition of HLA-DQ2/DQ8 peptide binding.