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Binding Too Tight

 
  December, 10 2008 19:33
your information resource in human molecular genetics
 
     

An explanation for the link between a certain tissue type and coeliac disease is described in Nature. The type has previously been linked to the disease but until now researchers have struggled to explain why.

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.


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