Abstract

In the last decade a wealth of information has become available enabling the study of CD8 + T cell responses to many native epitopes of poxviruses. Our laboratory has been using this information to understand several aspects of CD8 + T cell responses to poxviruses and vaccinia virus (VACV) vaccines. First, we are interested in understanding the hierarchy of responses, or why some epitopes elicit stronger responses than others (often called immunodominance) and why this can change with differing infection conditions. Second, we are studying how these epitopes are presented to CD8 + T cells when responses are initiated (or primed) and the extent to which this varies by VACV strain. Third, we are seeking a quantitative understanding of how the amount of each epitope displayed on an infected cell relates to the abundance of its parent protein and its position in the immunodominance hierarchy. Finally, and most related to the title, we have explored the extent to which two recently described inhibitors of CD8 + T cell epitope presentation from cowpox virus suppress the priming of immune responses. The major finding of this last study is that the overall effect of these ‘immune evasion’ genes is surprisingly limited. This talk will present data from across these areas of research with a particular focus on the inability of poxviruses to escape the vigilance of the immune system, even when armed with apparently effective tools of evasion.