The Role of the Gluten-Derived Peptide Gliadin in Celiac Disease

Gluten is a prolamin (gluten protein) found primarily in wheat that has been associated with celiac disease. What is relatively unknown to the general population about gluten is that a certain component of gluten, gliadin appears to be the primary cause of celiac disease. Gliadin is a peptide contained within glutencontaining foods and, upon ingestion, causes inflammation due to stimulation of helper T-cells. It has been estimated that approximately 60,000 annually suffer from celiac disease, suggesting this disease to likely be the common geneticallylinked disorder in the United States [1]. The human leukocyte antigens (HLA) DQ2 and DQ8 genes are part of the major histocompatibility complex (MHC), and celiac disease is robustly associated with the up-regulation of these genes. The recognition of T-cells to their respective pathogen relies on the function of MHC molecules to bind peptide fragments for display on the cell surface. The association between celiac disease and HLA is linked to the heightened ability of DQ2 to bind the gluten peptides which have survived deamination by tissue transglutaminase (tTG) during digestion [2]. This T-cell response to HLA-DQ2/DQ8 restricted gluten peptides occurs only in celiac patients and not in healthy individuals. The HLA-DQ2/DQ8 receptor favors peptides that contain one or more negatively-charged amino acids which are not present in gluten peptides, but can be introduced due to the activity of tTG, which is an enzyme that converts glutamine residues into negatively-charged glutamic acid residues. Gliadin peptides, with their high proline and glutamine content, are ideal substrates for the tTG activity, which is critical for the creation of active T-cell epitopes involved in celiac disease. Several DQ2and DQ8-restricted T-cell epitopes have been identified, particularly in wheat gluten. An individual is genetically predisposed to celiac disease due to these HLA-DQ2 and DQ8 genes. Gliadin has been shown to cause an inflammatory response in the small intestine of these predisposed individuals that have nutrient deficient consequences, among other things.