Immunodominant CD8+ T cell responses to HIV-1 infection : 'the good and the bad'

Many lines of evidence indicate that CD8+ T cells are important in the control of HIV-1 infection and this has led to much vaccine research focused at eliciting virus specific CTL. However to date, the few large-scale trials of HIV-1 vaccines designed to elicit CD8+ T cells have produced disappointing results. This has highlighted our incomplete knowledge of the factors that determine if such cells are capable of viral control. The aim of this thesis is to further characterise qualitative aspects of HIV-1 specific CTL that are associated with both good and bad anti-viral activity. HIV-1 specific CTL responses were investigated in three ways. Firstly, by longitudinally analysing an immunodominant HLA-B*08 restricted CD8+ T cell response in a single rapid progression patient. Secondly, HLA-B*40 restricted CTL responses to HIV-1 where characterised within a Chinese slow progressor cohort. Lastly, factors that affect the processing and presentation of certain overlapping HIV-1 specific CD8+ T cell epitopes were examined. The results of these studies reveal that subtle variations in both host and viral proteins can have a substantial impact on virus specific CTL and in turn may impact on the outcome of disease. The generation of HIV-1 specific CD8+ T cells is a complex process affected by many variables including the viral sequence of epitope flanking regions as well as polymorphisms in the proteins involved in antigen processing and presentation. To add a further layer of complexity, it appears that HIV-1 virus specific CTL can modulate their functionality throughout the course of infection. Such factors should therefore be taken into account during HIV-1 vaccine design.EThOS - Electronic Theses Online ServiceGBUnited Kingdo