We aim to construct specific deletion mutants of one or more serpins of ectromelia and will analyze their virulence in the natural mouse host. Thus, we hope, to determine their true biological function as a possible evasion mechanism from cytolytic lymphocyte mediated control. We also aim to gain an understanding as to the contribution of the Fas pathway of cellular cytotoxicity in recovery from a variety of viral infections. This is particularly relevant in the light of our recent findings which showed that in the absence of a functional granule exocytosis pathway, Tc cells induce Fas expression on previously Fas negative target cells. One further aim is to elucidate if this Fas induction is a general means of limiting antigen in a feedback loop to regulate Tc cell clonal expansion.
Immunological memory underpins all vaccine strategies.
The vast majority of vaccines at present at use are protective as a result of B cell memory and antibody responses. Although T cell memory was first described over fifty years ago much remains to be learned about the biochemical and cellular basis of the phenomenon. We do not have detailed knowledge of the cellular events which lead to the establishment of T cell memory. We are not even able to identify a memory Tc cell phenotype precisely. Most progress has been made in analyzing the general functional properties and activation requirements of memory T cells.