During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8 T cells by 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 mice, mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against infection. However, similar to mice, 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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6655551 | PMC |
http://dx.doi.org/10.1126/science.aat5030 | DOI Listing |
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