Single cell genomics identifies IRF pioneering factors as key regulators of virus-specific CD8+ T cell differentiation
Presentation Time: 08:30 AM - 08:45 AM
Abstract ID: 4247 - B
Presenting Author:
Stephen J Turner , Professor at Monash University, Australia
Abstract:
Naïve CD8+ T cell activation requires the integration of T cell receptor signalling (Signal 1), co-stimulation (signal 2) and receipt of extrinsic inflammatory signals (Signal 3). All this initiates a program of proliferation and differentiation required for optimal pathogen control and establishment of immunological memory. Importantly, precisely how these signals influence programming of CD8+ T cell responsiveness are not fully understood. We have interrogated transcriptional and chromatin changes at a single cell level induced by CD8+ cell activation early after influenza A virus infection. Integrated analysis demonstrated that early changes in both chromatin accessibility and transcriptional signatures can occur prior to first cell division, and are in part, driven by extrinsic inflammatory signals such as type I IFN. We demonstrate that type IFN signaling prior to first cell division induces upregulation of Interferon Response Factors (IRFs), which in turn acts as a pioneering factors and remodel chromatin structures to promote more effective T cell activation. Utilizing a combination of IRF CUT&TAG and IRF CRISPR deletion in primary CD8+ T cells, we explored the genomic targets and functional impact of IRF chromatin remodeling on subsequent CD8+ T cell differentiation. These data demonstrate that a primary function for signal 3 inflammatory cytokines is to prime naïve CD8+ T cell chromatin structure prior to TCR engagement to ensure optimal responsiveness.
Single cell genomics identifies IRF pioneering factors as key regulators of virus-specific CD8+ T cell differentiation
Category
Poster and Podium (Block Symposium)