| Literature DB >> 30409884 |
Derek J Theisen1, Jesse T Davidson1,2, Carlos G Briseño1, Marco Gargaro3, Elvin J Lauron4, Qiuling Wang5, Pritesh Desai1,5, Vivek Durai1, Prachi Bagadia1, Joshua R Brickner1, Wandy L Beatty5, Herbert W Virgin1,6, William E Gillanders2,7, Nima Mosammaparast1, Michael S Diamond1,5,8,9, L David Sibley5, Wayne Yokoyama4, Robert D Schreiber1,9, Theresa L Murphy1, Kenneth M Murphy10,11.
Abstract
During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain-containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3 -/- mice, Wdfy4 -/- mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3 -/- mice, Wdfy4 -/- mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.Entities:
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Year: 2018 PMID： 30409884 PMCID： PMC6655551 DOI： 10.1126/science.aat5030
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714