Recognising a foreign invader as a potential threat is a key first step in the function of our immune system. This role is typically performed by a variety of T cells in our body that are capable of recognising different kinds of antigens. The Recognition theme focuses on visualising how three different classes of molecules, indicative of a potential threat, are presented to and detected by our immune system. The three classes of molecules are: (a) peptides, (b) lipids, and (c) metabolites.
Exploring the Biomedical Mechanisms Behind Celiac Disease
New findings suggest that a specific group of T cells are likely to contribute significantly to the symptoms associated with gluten intolerance.
An international research team has discovered a group of T cell receptors present in the disease-affected tissue of one of the two primary genotypes associated with celiac disease. Led by scientists at Monash University and Leiden University Medical Centre, the team found two populations of T cells that were undetectable in samples from patients on a gluten-free diet but that expanded rapidly following antigenic stimulation.
By identifying and characterising the relevant antigen-specific T cells in biopsy samples from celiac patients, the researchers have started to prepare the groundwork for future prophylactic or therapeutic interventions for this common disease of the small intestine.
The team obtained polyclonal gluten-specific T cell lines from the small intestines of four adult patients with celiac disease, from which they generated clones. They then procured the crystal structures of the antigens bound to the T cell receptors, and solved them using an advanced molecular replacement programme.
The results indicate that the emergence and proliferation of these specific T cells are implicated in the onset of celiac disease – and they may also explain variations in the symptoms experienced by patients. Analysis of the crystal structures also revealed the vital role of an amino acid called arginine in the region where T cell receptors bind to the antigen. While it is too premature to consider clinical applications, the work could eventually contribute to the development of novel compounds that target the T cell receptors described in the study, with the elimination of these cells potentially forming a long-lasting treatment for celiac disease.
“Our group is focused on understanding a disease of direct human relevance that ultimately may lead to translational outcomes,” says Professor Jamie Rossjohn, an Imaging CoE researcher and one of the study’s authors. “Our next steps are to continue our work understanding the basic biomedical mechanisms underpinning celiac disease.”
The paper was published in June 2015 in the Journal of Immunology. In a notable accolade, it featured in the ‘In this Issue’ section, which highlights articles considered to be among the top 10% of those published in the journal.
Dale Godfrey and Jamie Rossjohn
Stephanie Gras, Ranjeny Thomas, Thomas Caradoc-Davies, Andrew Peele, Daniel Pellicci