Quantitative studies of the presentation of viral antigens to the immune system (especially CD8+ T cells) during infection. Our interest here is in understanding how the levels of presentation relate to anti-viral immune responses and in turn how this information can be exploited in vaccine development.
CD8+ T cells are an important weapon used by humans and other mammals to fight infection. In our laboratory, we use vaccinia virus as a model to dissect the factors that contribute to the strength and specificity of anti-viral T cell responses. An important aspect of CD8+ T cell specificity is that responses are not distributed equally amongst the various parts of a virus that are recognised. This is known as immunodominance. The way in which the virus proteins are processed inside infected cells to yeild the short peptides ultimately recognised by T cells can affect immunodominance. In addition, the number of T cells available at the time of infection that can recognise each peptide plays an important role. In a series of related projects we are examining aspects of infection or immunisation that result in changes in immunodominance for complex reasons. These include unexpected changes seen when very closely related strains of the same virus are used, or when different sites of infection are studied. The outcome of this work has a bearing on interpretation of preclinical vaccine studies and also our understanding of how immune responses are generated during virus infection. (Image: an example of flow cytometry data showing the expression of CD62L [x-axis] and granzyme B [y-axis] on CD8+ T cells during immunisation with vaccinia virus)