Format

Send to

Choose Destination
Science. 2018 Nov 9;362(6415):694-699. doi: 10.1126/science.aat5030.

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

Author information

1
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
2
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
3
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
4
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Vir Biotechnology, San Francisco, CA, USA.
7
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110, USA.
8
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
9
Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
10
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. kmurphy@wustl.edu.
11
Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
#
Contributed equally

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.

PMID:
30409884
DOI:
10.1126/science.aat5030

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center