Project Summary Mortality from infectious diseases remains a leading cause of death worldwide, making the development of new vaccines an important priority of biomedical research. Immunologic memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Traditional vaccination strategies are very effective at generating neutralizing antibodies against bacteria and viruses. However, a vaccine capable of generating robust T lymphocyte memory is still beyond our research, due, in part, to an incomplete understanding of the molecular basis of lymphocyte fate specification. In this proposal, we will develop single-cell approaches to study specification of lymphocyte fates in response to microbial infection.