Mechanisms regulating antigen presentation during primary and recall responses of T cells following pathogen infection

免疫系统的主要作用是遏制病原体、癌细胞和感染。这依赖于产生长期记忆的CD8+杀伤T淋巴细胞。一般来说，在病原体生长相对较快的急性感染中，这一过程是有效的。然而，疱疹病毒和结核病等病原体生长较慢，无法有效地激活杀伤T细胞，以至于它们逃避免疫系统，永远不会完全从体内清除。这些后一种感染会导致持续性或慢性感染。我们的工作将致力于揭开杀手T细胞如何被有效激活的机制，以及导致这些细胞在持续感染中无法类似激活的因素。这项建议中描述的研究的中心目的是了解不同病原体利用的机制，以产生不同的记忆杀手T细胞群，使我们能够对我们每天可能遇到的过多病原体做出反应。这些研究将提高我们对抗原提呈细胞和杀伤T淋巴细胞如何确保维持免疫反应的理解，并可能确定当免疫反应出错时可以针对的检查点来调节免疫反应。

The primary role of the immune system is the containment of pathogens, cancer cells and infections. This depends on generating long-lived memory CD8+ killer T lymphocytes. Generally this process is achieved efficiently in acute infections in which the pathogen grows relatively rapidly. However, pathogens such as herpes viruses and tuberculosis grow more slowly, fail to efficiently activate the killer T cells such that they elude the immune system and are never completely removed from the body. These latter infections result in persistent or chronic infections. Our work will endeavour to unravel the mechanisms that underlie how a killer T cell is effectively activated and the factors that contribute to failure of these cells to be similarly activated in a persistent infection. The central aim of the studies described in this proposal is to understand the mechanisms utilized by different pathogens to generate the diverse population of memory killer T cells that allow us to respond to the plethora of pathogens we might encounter every day. These studies will improve our understanding of how antigen presenting cells and killer T lymphocytes ensure an immune response is maintained and may identify checkpoints that could be targeted to modulate the immune response when it goes wrong.