Antigen presentation, recognition and the immune response

免疫的早期事件需要各种分子相互作用。我们将研究其中一些相互作用的结构和生物物理基础，包括与移植排斥和自身免疫相关的那些。我们将探索免疫反应基因变异对免疫逃避和疾病易感性的影响。我们的基础研究将确定免疫系统区分不同自身和微生物相关决定因素的机制。我们将讨论一种名为Tapasin的免疫分子运行的结构和生化基础，并揭示一些病毒如何逃避该分子的功能，从而允许它们的免疫逃避的基础。我们还将探索在面筋过敏症的人源化模型中使用称为多肽的修饰小蛋白，类似于乳糜泻。我们将研究人类天然免疫系统识别和排斥移植物的分子基础。这是对旨在提高临床移植排斥反应预测的工作的补充。树突状细胞在免疫中起着核心作用，负责捕获来自微生物或自身组织的物质，并将其呈递给免疫系统的细胞。我们的项目将研究不同树突状细胞亚型的发育和免疫功能。我们将确定它们在维持免疫耐受性和诱导对几种病原体的免疫方面的相对贡献，包括单纯疱疹病毒和疟疾。我们已经发现的新型树突状细胞表面分子将被测试它们增强疫苗有效性的能力。总体而言，该计划利用了一系列广泛的免疫学技术，旨在剖析各种免疫系统细胞类型的发育和功能，并确定参与免疫的重要细胞表面分子之间的结构-功能关系。

The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will address the structural and biochemical basis for operation of an immune molecule called tapasin and unravel the basis for how some viruses escape the function of this molecule, thus allowing their immune evasion. We will also explore the use of modified small proteins called peptides in a humanized model of gluten hypersensitivity resembling that of Celiac disease. The molecular basis of the natural human immune system's capacity to recognise and reject grafts will be examined. This complements work aimed at improving the prediction of clinical graft rejection in transplantation. Dendritic cells play a central role in immunity, responsible for capturing material, whether from micro-organisms or self tissues, and presenting it to cells of the immune system. Our program will study the development and immunological function of the different dendritic cell subtypes. We will determine the relative contribution of each to the maintenance of immune tolerance and to the induction of immunity to several pathogens, including herpes simplex virus and malaria. Novel dendritic cell surface molecules that we have discovered will be tested for their ability to enhance the effectiveness of vaccines. Overall, this program utilises a broad array of immunological techniques designed to dissect the development and function of various immune system cell types and determine the structure-function relationships between important cell surface molecules involved in immunity.