Aspects of CD8+ T cell and NK cell recognition that impact on MHC class I associations with HIV-1 disease progression

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Over 50% of the 40 Million people estimated to be infected with HIV-1 live in sub-Saharan Africa alone. With only a small proportion of developing countries having access to the anti-retroviral therapies readily available in the Western world, an alternative approach is urgently required to control the spread of this virus. One promising strategy is the production of a vaccine to either prevent infection and/or augment immunity against HIV-1 during disease. Cells of the immune system, namely CD8+ T lymphocytes, effectively control the growth of HIV-1, and many vaccines in current clinical trials are designed to evoke CD8+ T cell mediated immunity.The interaction between this virus and the host s immune system is complex, however, and the level of viral control is variable in HIV-1 infected individuals. This, in turn, makes it difficult to design a truly effective HIV vaccine. Major Histocompatibility Complex (MHC) class I molecules represent important host factors that influence disease outcome - these molecules direct the CD8+ T cell responses against HIV-1, and therefore influence disease severity. By studying the fine details of diverse CD8+ T cell responses in distinct HIV-1 infected patient groups I hope to identify the reasons why some CD8+ T cell responses are more effective than others in controlling the replication of HIV-1. Certain MHC class I molecules also interact with different cells of the immune system, namely Natural Killer (NK) cells, and this also impacts on disease dynamics in HIV-1 infection. I also wish to study aspects of NK and MHC interactions that might explain this phenomenon, as this could influence the design and implementation of future vaccine regimens.