Binding Too Tight

Coeliac disease is caused by an inappropriate immune reaction to gluten - a protein found in wheat - and is more common in people of a certain tissue type. An individual's tissue type is defined by a family of proteins expressed on the surface of cells, known as the major histocompatibility complex (MHC). It has long been known that a certain type of MHC - HLA-DQ8 - predisposes to coeliac disease but it was not clear why.

The MHC acts as a molecular display case, presenting pieces of proteins to the immune system, which then decides whether or not to react. Bana Jabri and colleagues find that the structure of HLA-DQ8 allows it to bind to fragments of gluten that cannot bind to other types of MHC. These are recognized by a population of T cells, which set about initiating an adverse immune reaction. This immune reaction also activates an enzyme - transglutaminase - that modifies the structure of gluten fragments such that they are able to bind more tightly to HLA-DQ8. The team find that this activates more T cells and establishes a vicious cycle of disease.

Jabri and colleagues believe that similar mechanisms could explain links between tissue types and other autoimmune diseases.

CONTACT

Bana Jabri (University of Chicago, IL, USA)
E-mail: bjabri@bsd.uchicago.edu

(C) Nature press release.

Message posted by: Trevor M. D'Souza