Browsing by Author "van Beek, Jasper J.P."

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    Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential
    (Elsevier, 2021-11) Rogers, Dakota; Sood, Aditi; Wang, HanChen; van Beek, Jasper J.P.; Rademaker, Thomas J.; Artusa, Patricio; Schneider, Caitlin; Shen, Connie; Wong, Dylan C.; Bhagrath, Aanya; Lebel, Marie-Ève; Condotta, Stephanie A.; Richer, Martin J.; Martins, Andrew J.; Tsang, John S.; Barreiro, Luis B.; François, Paul; Langlais, David; Melichar, Heather J.; Textor, Johannes; Mandl, Judith N.; Microbiology and Immunology, School of Medicine
    CD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probe the heterogeneity present among naive CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and chromatin landscape differences. Single-cell RNA sequencing shows that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a readout of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naive CD4+ T cells impact follicular helper T (TFH) cell versus non-TFH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naive CD4+ T cell chromatin landscapes that ultimately shape their effector potential.