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

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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.