Molecular mechanisms of early memory CD8+ T cell reactivation in vaccinated hosts 4399

Description CD8+ T cells have the unique capacity to efficiently detect and eliminate intracellular pathogen-infected cells and tumors. One important functional feature of memory CD8+ T (Tm) cells that we and other characterized in prior works, is their ability to provide early protection during reactivation prior to clonal expansion, by enabling the rapid activation and mobilization of innate immune defenses. However, the molecular transcriptional and epigenetic mechanisms underlying CD8+ Tm cell rapid cognate antigen (Ag) dependent reactivation in vivo are poorly understood. Through single cell transcriptomic and chromatin accessibility analyses of Tm cells early post cognate Ag reactivation, we discovered that a small set of transcription factors (TF) are differentially regulated and have enriched binding sites in newly accessible promoters. We hypothesize that these TF drive the early protective effector program that mediate CD8+ Tm cell-dependent host protection. We are using high dimensional flow cytometry and multiplex assays to explore the kinetic of expression of cognate Ag-dependent TF expression, how they regulate each other and how they control distinct effector functions of the Tm cells. We are also testing the roles of these TF using in vitro and in vivo gain and loss of function approaches. We will present data offering new insights into the transcriptional regulation required for an effective CD8+ Tm cell response. Funding Sources Supported by NIH R01 AI103338 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)