Antigen presentation, recognition and the immune response

免疫的早期事件需要各种分子的相互作用。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相互作用。我们将探讨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的自我和微生物相关决定因素的机制。我们将讨论一种叫做tapasin的免疫分子运作的结构和生化基础，并揭示一些病毒如何逃避这种分子的功能，从而使它们能够免疫逃避的基础。我们还将探索在类似乳糜泻的谷蛋白过敏人源化模型中使用修饰的小蛋白肽。自然人类免疫系统识别和排斥移植物的能力的分子基础将被检查。这补充了旨在改善临床移植排斥预测的工作。树突状细胞在免疫系统中起着核心作用，负责从微生物或自身组织中捕获物质，并将其呈现给免疫系统的细胞。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。我们将确定每一种对维持免疫耐受和诱导对几种病原体（包括单纯疱疹病毒和疟疾）的免疫的相对贡献。我们发现的新型树突细胞表面分子将被测试其增强疫苗有效性的能力。总体而言，该计划利用广泛的免疫学技术来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.