DESCRIPTION (provided by applicant): Following exposure to antigen, host lymphocytes go through a process of differentiation resulting in the generation of antigen-specific memory lymphocytes. Memory T cells provide a pool of antigen-specific lymphocytes capable of rapid response following antigen re-exposure. While T cell memory is beginning to be understood at the cellular level, the transcriptional regulation involved in memory is poorly understood. Recent genetic data have identified bcl-6, a sequence-specific transcriptional repressor, as a regulator of CD8 T cell memory. This proposal will focus on the role of bcl-6 in the generation of CD8 memory T cells, by defining the kinetics and function of bcl-6 in memory CD8 T cell development and survival. These studies will provide insight into the molecular regulation of CD8 T cell memory. Furthermore, they may identify specific methods to accentuate CD8 T cell memory to aid in clearance of infection, or to prevent inappropriate development of autoreactive CD8 memory T cells.