Development and function of dendritic cell subsets
Batf3-dependent CD8α+ dendritic cells (cDC1) capture and present antigens derived from tumors and virally infected cells, a process called cross-presentation. We established a functional CRISPR screen for novel regulators of cross-presentation in primary cDC1 generated by FLT3L cultures of Cas9 transgenic Kit-high bone marrow progenitors and a candidate based selection of target genes. We identified a BEACH-domain containing that was essential for cross-presentation of cell-associated antigens by cDC1, not required for MHC class II presentation or cross-presentation by monocyte-derived DCs. Mice deficient in this gene develop normal populations of cDC1 that produce IL-12 and can protect against Toxoplasma gondii infection, but fail to prime virus-specific CD8+ T cells in vivo or induce tumor rejection. Current findings on this gene will be discussed.
Professor, Pathology & Immunology
Washington University School of Medicine, Dept of Pathology and Immunology