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

Derek J. Theisen, Jesse T. Davidson, Carlos G. Briseño, Marco Gargaro, Elvin J. Lauron, Qiuling Wang, Pritesh Desai, Vivek Durai, Prachi Bagadia, Joshua R. Brickner, Wandy L. Beatty, Herbert W. Virgin, William E. Gillanders, Nima Mosammaparast, Michael S. Diamond, L. David Sibley, Wayne Yokoyama, Robert D. Schreiber, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8a+/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.

Original languageEnglish
Pages (from-to)694-699
Number of pages6
JournalScience
Volume362
Issue number6415
DOIs
StatePublished - Nov 9 2018

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    Theisen, D. J., Davidson, J. T., Briseño, C. G., Gargaro, M., Lauron, E. J., Wang, Q., Desai, P., Durai, V., Bagadia, P., Brickner, J. R., Beatty, W. L., Virgin, H. W., Gillanders, W. E., Mosammaparast, N., Diamond, M. S., Sibley, L. D., Yokoyama, W., Schreiber, R. D., Murphy, T. L., & Murphy, K. M. (2018). WDFY4 is required for cross-presentation in response to viral and tumor antigens. Science, 362(6415), 694-699. https://doi.org/10.1126/science.aat5030