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. |