Prolonged presentation prompts Coeliac disease

A reason why individuals with Coeliac disease develop a food allergy to wheat proteins is reported online in Nature Immunology. By increasing the amount of time wheat peptides are presented to immune cells, more cells are activated and trigger inflammatory reactions, which could be a paradigm for other allergic or autoimmune responses as well.

Coeliac disease patients cannot tolerate ingestion of wheat products, which prompts a severe gastrointestinal immune response. Patients must therefore adhere to a restricted diet to avoid triggering this inflammatory response.

Ludvig Sollid and his team looked at why people who carry the antigen HLA-DQ2.5, which was previously associated with higher risk of Coeliac disease, are more prone to react to wheat proteins than individuals who carry the closely related HLA-DQ2.2 version of the gene. They find a single amino acid difference in the peptide binding groove of DQ2.5 and DQ2.2 allows peptides to be presented to immune cells for a longer duration. These differences mean that more stable binding to the wheat peptides occurs in people with the DQ2.5 molecule leading to an intolerance to wheat gluten.

The authors suggest this increased peptide dwell time might also explain other autoimmune diseases associated with particular HLA alleles.