The molecular heart of celiac disease revealed

April 29, 2014

Australian, US and Dutch researchers have determined the molecular details of the interaction between the immune system and gluten that triggers celiac disease. Their work opens the way to potential treatments and diagnostics.

Monash, Melbourne and Leiden university researchers, in collaboration with colleagues from a Boston-based company, have described the molecular basis of how most of the (T cells) that induce lock onto gliadin, a component of gluten, thereby triggering inflammation of the lining of the small intestine. This is what gives many celiac sufferers symptoms similar to food poisoning after eating a slice of toast.

"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 ," says Dr Hugh Reid of Monash University. Dr Reid and fellow Australian-based researchers collaborated in the study with Prof Frits Koning from the Leiden University Medical Center in the Netherlands and with US company, ImmusanT.

Celiac disease is an immune system intolerance of gluten, a protein which occurs naturally in grains such as wheat, rye, barley and oats, and therefore is typically found in bread, pastries and cakes. The problem is that certain T cells regard as a foreign and potentially toxic substance, and initiate action against it. This inflammatory process is triggered when these T bind to gliadin.

Today's paper, published in Nature Structural and Molecular Biology, explains what's happening in the overwhelming majority of celiac disease sufferers, the ninety-five percent who carry a gene for the particular protein, HLA-DQ2. In 2012, the research team found a similar trigger for the other five per cent who have HLA–DQ8, another celiac disease susceptibility gene.

With the assistance of the Australian Synchrotron, the researchers were able to determine the structure of the molecular complexes that form during the interaction between T cell receptor and gliadin. Armed with this information, they were able to work out what was important in the T cell response.

"This research is a classic example of what the new Australian Research Council Centre of Excellence in Advanced Molecular Imaging strives to achieve," says Prof Rossjohn from Monash University, "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."

Ultimately, the insight provided by the research will assist the development of a blood test and a therapeutic vaccine for patients with celiac disease who carry the gene HLA-DQ2.

Explore further: Research gives new insight into coeliac disease

More information: "T-cell receptor recognition of HLA-DQ2–gliadin complexes associated with celiac disease." Jan Petersen, et al. Nature Structural & Molecular Biology (2014) DOI: 10.1038/nsmb.2817. Received 12 February 2014 Accepted 28 March 2014 Published online 28 April 2014

Related Stories

Research gives new insight into coeliac disease

October 11, 2012

For the first time, scientists have visualised an interaction between gluten and T-cells of the immune system, providing insight into how coeliac disease, which affects approximately 1 in 133 people, is triggered.

A natural protein, Elafin, against gluten intolerance?

April 8, 2014

Scientists from INRA and INSERM (France) in collaboration with scientists from McMaster University (Canada) and the Ecole polytechnique fédérale of Zurich (Switzerland) have shown that Elafin, a human protein, plays a key ...

Bowel illnesses sometimes coincide in kids

April 21, 2014

(HealthDay)—Children suffering from irritable bowel syndrome are four times more likely than other kids to have a condition called celiac disease—an allergy to gluten—Italian researchers report.

Recommended for you

Researchers reveal role of gene in IBD

April 26, 2017

Inside a healthy gut, bacteria and immune cells maintain a delicate balance. If that balance is disturbed, a condition called inflammatory bowel disease or IBD can result. Patients with IBD can experience diarrhea, abdominal ...

When liver immune cells turn bad

April 21, 2017

A high-fat diet and obesity turn "hero" virus-fighting liver immune cells "rogue", leading to insulin resistance, a condition that often results in type 2 diabetes, according to research published today in Science Immunology.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Apr 29, 2014
As a Celiac, two excited thumbs up! I would be absolutely thrilled if this research led to the immune system being able to be turned off in regard to gluten.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.