Structure and Function of Receptors for IgG (FcgammaR)

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How FcR function in normal and destructive immunity: This research project is studying one of the most important receptor families of inflammatory white blood cells known in immunology. These receptors called Fc Receptors (FcR) bind complexes of specialised proteins called antibodies with foreign antigens, i.e. bacteria, viruses, called immune complexes. As a direct consequence of this binding, a chain of events in inflammatory white blood cells is set in motion, leading to the destruction of foreign pathogens, however in autoimmune diseases this same processes leads to the severe inflammation causing destruction of joints in rheumatoid arthritis and kidneys in glomerulonephritis or allergies, bleeding disorders. Our studies are aimed at understanding the very first events that initiate this inflammatory cascade, i.e. how immune complexes bind to FcR and having bound these, how these receptors are organised to initiate the inflammatory cascade. Our studies will use new techniques such as X-ray crystallography to take 3D photographs of FcR interacting with immune complexes and genetic engineering studies to validate our 3D photographs. If we understand how immune complexes bind to FcR and how the receptors are organised on the cell membrane, we will be able to apply this information to the development of new treatments that either interfere with immune complex binding or receptor organisation. Although these concepts are well established in other fields e.g. growth hormone receptors, very little is known about the organisation of receptors involved directly in immunity. These novel studies will provide us with powerfully useful insights into the first steps in antibody driven tissue destruction.