Research update: T-cell epitope mapping

Comprehensive gluten T-cell epitope mapping in coeliac disease

Doctor Robert Anderson MB ChB BMedSc PhD FRACP
Autoimmunity and Transplantation Division, Walter and Eliza Hall Institute, Australia

Summary
It is an unfortunate mistake that the immune system recognises and reacts to gluten in people with coeliac disease. The immune cells that sense gluten and damage the intestine, T-cells, detect only the very specific short fragments (epitopes) of gluten proteins. Understanding which gluten fragments cause coeliac disease would enable new tests to diagnose coeliac disease, design of non-toxic gluten, and may even allow new treatments that could desensitise the immune system to gluten in the same way that desensitisation therapy works for allergy.

Understanding of the gluten fragments causing coeliac disease is improving but it is still incomplete. It is still unclear which gluten components are important in real-life rather than for T-cells in the laboratory, and whether everyone with coeliac disease reacts to the same components. We have developed a simple test that can pin-point the gluten fragments recognised by any individual with coeliac disease. Our work at Oxford University showed that when people with coeliac disease normally on a gluten-free diet deliberately eat gluten, T-cells reacting to gluten emerge from the intestinal tissues and for a few days are found in the blood. With the help of over 200 volunteers with coeliac disease and a library of short gluten fragments encompassing all known gluten proteins, we have been able to map all the regions of gluten in wheat, barley, rye and oats that stimulate T-cells.

The project we will undertake with the assistance of Coeliac UK is to find the most potent epitopes that can be used in diagnostic tests, food tests, and desensitisation therapy. If successful, the study would lead to clinical trials and the prospect of alternatives to endoscopies for diagnosis, and an alternative to a gluten-free diet.