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Transcriptional and Epigenetic Networks Driving CD8+ T Cell Differentiation

From Q-bio

The formation of immunological memory is guided by a variety of factors spanning environmental, cellular, and molecular cues that, during the early response to infection, provide the necessary conditions for lineage commitment to disparate fates in the CD8 T cell population. Different functional subsets form throughout the CD8 T cell response, with varying localization, effector, proliferative, and protective properties thanks to the combinatorial action of various transcription factors (TFs) that establish distinct transcriptomes. Master regulators such as T-bet and FoxO1 promote the formation of effector subsets with varying potential to form immunological memory - driving terminal effector (TE) and memory precursor (MP) CD8 T cell differentiation, respectively. However, TF activity is dependent on chromatin accessibility, and thus is a function of the epigenomic landscape. The interplay between TFs and the epigenomic landscape in driving MP vs. TE cell fates creates differential gene regulatory network (GRN), the details of which are as yet unclear. Our work begins to dissect these GRNs in forming potent immunological memory, with the goal of predicting key regulatory nodes involved in successful and dysfunctional immune responses contributing to healthy or disease states, respectively.