Determinant spreading and the role of the MHC class II region in systemic and organ-specific autoimmunity

自身免疫性疾病是影响成人人群的最重要的疾病之一。在这些疾病中，免疫系统损害器官和组织，产生广泛的病理（全身性自身免疫，如红斑狼疮）或局部疾病（器官特异性自身免疫，如胰岛素依赖性糖尿病）。我们对免疫系统如何以及为什么攻击人体自身组织知之甚少。这项研究探讨了抗体和T淋巴细胞是如何形成的，以对抗体内细胞内的成分。这项研究涉及通过引入影响自身免疫发展的关键人类基因来对小鼠进行遗传修饰。通过这种方式，这些人类基因的作用可以通过实验来检验，而不必专门对患者进行研究。我们还希望这些小鼠在创建乳糜泻和胰岛素依赖型糖尿病的新模型方面可能很重要。拟议中的实验应该告诉我们这些基因如何促进自身免疫性疾病的发展。这种理解可能是相关的设计治疗和干预措施，以防止自身免疫性疾病。

Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.