WDFY4 is required for cross-presentation in response to viral and tumor antigens.
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.
Mesh Terms:
Animals, Antigens, Neoplasm, Antigens, Viral, Basic-Leucine Zipper Transcription Factors, CD8-Positive T-Lymphocytes, CRISPR-Cas Systems, Cross-Priming, Genetic Testing, Humans, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Repressor Proteins, Toxoplasma, Toxoplasmosis
Animals, Antigens, Neoplasm, Antigens, Viral, Basic-Leucine Zipper Transcription Factors, CD8-Positive T-Lymphocytes, CRISPR-Cas Systems, Cross-Priming, Genetic Testing, Humans, Mice, Mice, Inbred C57BL, Mice, Mutant Strains, Repressor Proteins, Toxoplasma, Toxoplasmosis
Science
Date: Dec. 09, 2017
PubMed ID: 30409884
View in: Pubmed Google Scholar
Download Curated Data For This Publication
216013
Switch View:
- Interactions 144