Scripps team IDs new target for autoimmune disease

A group of researchers at Scripps has pinpointed the specific genetic mutations at work in Type 1 diabetes, a breakthrough that offers a fresh target for drug developers active in autoimmune drug development.

Cases of Type 1 diabetes are triggered when T cells run amuck, attacking the body's cells and preventing them from producing insulin, a disease in the young that is currently treated with regular injections of insulin. Scripps Research Professor Luc Teyton and a colleague, Ian Wilson, led a team which found that mutated MHC molecules selected a unique subset of T cells that bound to it strongly. "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," says Teyton. "That's the big novelty of the paper--for 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."

"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," said Research Associate Adam Corper of the Wilson lab.

- read more about the study in the Journal of Clinical Investigation
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