TCF19 drives a broad transcriptional program that potentiates optimal innate and adaptive functions of antiviral NK cells

Natural killer (NK) cells are innate lymphocytes that play a critical role in host defense against viral infection. In addition to rapid effector cytokine production and direct cytotoxicity, NK cells exhibit features of adaptive immunity, including the capacity to undergo robust antigen-specific clonal proliferation and to generate immunological memory. However, the transcriptional programs and regulators governing dynamic NK cell responses to viral infection have not been fully uncovered. In this study, we identified Transcription factor 19 (TCF19) as a key driver of NK cell proliferation and calcium signaling in the context of mouse cytomegalovirus infection. Ablation of TCF19 was detrimental to NK cell clonal expansion and host protection against viral infection. Tcf19-/- NK cells were also unable to properly mobilize calcium downstream of antigen signaling to mediate cytotoxicity. Altogether, we find that TCF19 drives a transcriptional program that coordinates the innate and adaptive NK cell responses against viral infection. To investigate the role of TCF19 in NK cells during MCMV infection, we performed TCF19 scRNAseq using WT and TCF19-/- NK cells. scRNAseq was performed on FACS sorted mouse Ly49H+ CD49b+ NK cells.