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活动来清除微生物，这些细胞共同杀死和中和这些不受欢迎的客人。当微生物隐藏在人体细胞内时，它们仍然被一组T淋巴细胞探测到，这些T淋巴细胞具有特定的受体，用于仔细检查细胞表面的任何可能发出细胞内感染信号的变化。免疫系统在寻找感染迹象时总是保持警惕，当被称为抗原的分子被微生物释放并被人体细胞捕获时，感染迹象通常是明显的。这会激活淋巴细胞，产生能够清除微生物的免疫反应。即使在体内没有感染的情况下，淋巴细胞对人体细胞的检查也会持续进行。在细胞感染后，微生物抗原通过出现在细胞表面来揭示感染情况，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提呈的机制来实现的。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，首先被降解成称为多肽的较短分子。这一过程被称为抗原处理。在抗原处理过程中产生的一小部分肽被存在于所有细胞上的特殊受体捕获。这些受体被称为人类白细胞抗原或组织相容性分子。这个项目研究了调节人类白细胞抗原分子捕获多肽抗原的分子事件。主要的焦点是那些通过免疫系统激发杀手T细胞反应的多肽抗原。了解这些多肽是如何被选择呈现的，以及它们是如何被捕获并携带到细胞表面的，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(如在自身免疫中)是基本的。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.