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Publication : WDFY4 is required for cross-presentation in response to viral and tumor antigens.

First Author  Theisen DJ Year  2018
Journal  Science Volume  362
Issue  6415 Pages  694-699
PubMed ID  30409884 Mgi Jnum  J:266805
Mgi Id  MGI:6257237 Doi  10.1126/science.aat5030
Citation  Theisen DJ, et al. (2018) WDFY4 is required for cross-presentation in response to viral and tumor antigens. Science 362(6415):694-699
abstractText  During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8(+) T cells by Batf3-dependent CD8alpha(+)/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.
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