Defining the role of STAT1 acetylation in adaptive immunity.

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The immune system works by recognising pathogens as foreign and initiating a response that destroys the invader. In auto-immune disease, however, it is the host that is mistakenly thought to be foreign and so destroyed by the subsequent immune response. Both immune and auto-immune responses are dependent on an incredible expansion (>10,000fold) in the number of cells capable of recognising what is foreign. This expansion in number occurs by cellular proliferation. What is surprising is that such proliferation still occurs in environments that we would expect to be anti-proliferative because of their high levels of the anti-pathogen protein, interferon (IFN). This project tests the hypothesis that this proliferation can occur because the cells of the immune system modify the IFN signalling molecule STAT1. Experiments will test whether blocking this step prevents both protective immune responses and protects against the autoimmune disease, SLE. These experiments will also generate the materials necessary to test whether HIV owes part of its infectious success to its exploitation of this mechanism. The overall aim of the project is to reduce to a single biochemical event the complex physiological reactions that drive both immune protection and autoimmunity, in order to open new avenues for treatments.