A trigger for coeliac disease

Researchers have discovered how our immune cells and gluten interact at the amino acid level to trigger coeliac disease.

The molecular details of the interaction between the immune system and gluten have been revealed.

People with coeliac disease are intolerant to gluten, a protein that occurs naturally in grains such as wheat, rye, barley and oats. They react with symptoms similar to food poisoning after eating foods such as bread or biscuits containing wheat or rye.

The problem is that certain T cells of the immune system regard gluten as a foreign and potentially toxic substance, proceeding to trigger action against it and causing inflammation of the lining of the small intestine.

A collaboration involving Australian, US and Dutch researchers used X-ray crystallography to visualise the molecular interaction between the T cells that induce coeliac disease and gliadin, a component of gluten.

“We studied how different T cells bind to gliadin, a component of gluten. And when we looked closely we found the docking mechanism was similar. This provides us with a way to develop drugs that might reduce or turn off the immune response,” said Dr Hugh Reid from Monash University.

The research explains what’s happening in the overwhelming majority of coeliac disease sufferers, the 95% who carry a gene for the particular protein, HLA-DQ2. In 2012, the research team found a similar trigger for the other 5% who have HLA–DQ8, another coeliac disease susceptibility gene.

Using the Australian Synchrotron, the researchers determined the crystal structure of the molecular complexes that form during the interaction between T cell receptor and gliadin. They were then able to work out what was important in the T cell response.

“Using the latest imaging tools - from microscopes to the synchrotron - we can understand and influence the immune recognition events that trigger immune responses, both good and bad,” said Professor Jamie Rossjohn from Monash University.

The insights provided by the research will help in the development of a blood test and a therapeutic vaccine for patients with coeliac disease who carry the HLA-DQ2 gene.

Dr Reid and fellow Australian-based researchers collaborated in the study with Professor Frits Koning from the Leiden University Medical Center in the Netherlands and with US company ImmusanT.

The work was published in Nature Structural and Molecular Biology.