Structure and Function of Receptors for IgG (FcgammaR)

FcR如何在正常和破坏性免疫中发挥作用：本研究项目正在研究免疫学中已知的炎症白细胞最重要的受体家族之一。这些被称为Fc受体（FcR）的受体将称为抗体的特殊蛋白质复合物与外来抗原（即细菌、病毒）结合在一起，称为免疫复合物。这种结合的直接后果是，炎症性白细胞中的一系列事件被启动，导致外来病原体的破坏，然而在自身免疫性疾病中，同样的过程导致严重的炎症，导致类风湿关节炎的关节和肾小球肾炎或过敏的肾脏的破坏，出血性疾病。我们的研究旨在了解引发这种炎症级联反应的最初事件，即免疫复合物如何与FcR结合并结合这些受体，这些受体如何组织以启动炎症级联反应。我们的研究将使用新技术，如x射线晶体学，拍摄FcR与免疫复合物相互作用的3D照片和基因工程研究，以验证我们的3D照片。如果我们了解免疫复合物如何与FcR结合以及受体如何在细胞膜上组织，我们将能够将这些信息应用于开发干扰免疫复合物结合或受体组织的新疗法。虽然这些概念在生长激素受体等其他领域得到了很好的确立，但对直接参与免疫的受体的组织知之甚少。这些新颖的研究将为我们在抗体驱动的组织破坏的第一步提供强有力的有用的见解。

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.