Antigen selection in the MHC-restricted cellular immune response

人体的白细胞通过免疫淋巴细胞和其他细胞的作用来消灭微生物，这些细胞共同杀死和中和这些不速之客。当微生物隐藏在人体细胞内时，它们仍然会被一组T淋巴细胞检测到，这些T淋巴细胞具有特定的受体，可以仔细检查细胞表面的任何变化，以发现可能是细胞内感染的信号。免疫系统时刻保持警惕，寻找感染的迹象，这些迹象通常是在微生物释放抗原分子并被人体细胞捕获时出现的。这会激活淋巴细胞，从而产生能够消除微生物的免疫反应。即使在体内没有感染的情况下，淋巴细胞也会不断地对人体细胞进行检查。当一个细胞被感染后，微生物抗原会出现在细胞表面，被免疫系统的淋巴细胞检测到。这是通过一种叫做抗原呈递的机制发生的。在抗原呈递过程中，细胞内的蛋白质，包括任何入侵微生物的蛋白质，首先被降解成称为肽的较短分子。这个过程被称为抗原加工。抗原加工产生的肽的一小部分被存在于所有细胞中的特殊受体捕获。这些受体被称为HLA或组织相容性分子。本项目研究介导HLA分子捕获肽抗原的分子事件。主要的焦点是那些肽抗原，它们引起免疫系统的杀伤T细胞反应。了解这些肽如何被选择呈现，以及它们如何被捕获并携带到细胞表面，对于理解对微生物、肿瘤、过敏原、移植和自身组织的免疫反应（如自身免疫）是至关重要的。因此，这项研究具有重大的普遍意义。

The body's white cells eliminate microorganisms through the actions of immune lymphocytes and other cells which conspire to kill and neutralise these unwanted guests. When microorganisms hide inside the cells of the body they are still detected by a set of T lymphocytes which have specific receptors for scrutinising the surface of cells for any changes which might signal an intracellular infection. The immune system is ever vigilant in its search for signs of infection which are generally apparent when molecules called antigens are released by microorganisms and captured by the body's cells. This activates lymphocytes resulting in an immune response capable of eliminating the microorganisms. Scrutiny of the body's cells by lymphocytes occurs continuously even when there is no infection present in the body. Following infection of a cell, microbial antigens reveal the infection by their appearance on the cell surface where they are detected by the immune system's lymphocytes. This occurs through a mechanism called antigen presentation. During antigen presentation the proteins inside the cell, including those of any invading microorganism, are first degraded into shorter molecules called peptides. This event is called antigen processing. A fraction of the peptides created by antigen processing are captured by specialised receptors present on all cells. These receptors are called HLA or histocompatibility molecules. This project examines the molecular events which mediate the capture of peptide antigens by HLA molecules. The main focus is on those peptide antigens which elicit killer T cell responses by the immune system. A knowledge of how these peptides are selected for presentation and how they are captured and carried to the cell surface is fundamental to understanding immune responses to microorganisms, tumours, allergens, transplants and self tissues as in autoimmunity. Therefore the study is of great general relevance.