Antigen selection in the MHC-restricted cellular immune response

身体的白色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想要的客人。当微生物隐藏在人体细胞内时，它们仍然可以被一组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，这些变化可能是细胞内感染的信号。免疫系统在寻找感染的迹象时一直保持警惕，当被称为抗原的分子被微生物释放并被身体细胞捕获时，感染的迹象通常是明显的。这会激活淋巴细胞，导致能够消除微生物的免疫反应。淋巴细胞对身体细胞的检查即使在身体没有感染的情况下也会持续发生。在细胞感染后，微生物抗原通过它们在细胞表面上的出现来揭示感染，在那里它们被免疫系统的淋巴细胞检测到。这是通过一种称为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，首先被降解为称为肽的较短分子。这个过程称为抗原加工。由抗原加工产生的一部分肽被所有细胞上存在的专门受体捕获。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引起的杀伤T细胞免疫系统的反应。了解这些肽如何被选择用于呈递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、移植物和自身组织的免疫应答（如在自身免疫中）是至关重要的。因此，这项研究具有很大的普遍意义。

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.