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Scripps Research scientists reveal how genetic mutations may cause type 1 diabetes
Date:4/19/2010

ion 57 and consequently the surrounding region is more positively charged.

The result of this molecular change was that the mutated MHC molecules selected a unique subset of T cells that bound to it strongly, with "higher affinity." These T cells may overreact and potentially misidentify "self" peptides as dangerous rather than harmless.

"We found that the MHC region around position 57 can be seen by the T cell receptor," said Teyton. "That's the big novelty of the paperfor the first time, we show that it is not only essential for peptide binding, but also critical for the selection of T cells. Finally, we have an idea of why those particular MHC molecules are associated with disease."

Corper added, "What we have here is potentially a way of breaking 'tolerance'the mechanism where the immune system doesn't respond to self. Obviously, if that breaks down you get autoimmune disease."

The team is now investigating potential antibody or small molecule therapies that could target and correct mutated MHC.


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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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