The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens
Henry, C. M.
Buck, M. D.
Rogers, N. C.
Domart, M. C.
Ellison, C. J.
Thomas, D. C.
Reis, E. S. C.
AffiliationImmunobiology Laboratory, The Francis Crick Institute, London
MetadataShow full item record
AbstractType 1 conventional dendritic (cDC1) cells are necessary for cross-presentation of many viral and tumor antigens to CD8+ T cells. cDC1 cells can be identified in mice and humans by high expression of DNGR-1 (also known as CLEC9A), a receptor that binds dead-cell debris and facilitates XP of corpse-associated antigens. Here, we show that DNGR-1 is a dedicated XP receptor that signals upon ligand engagement to promote phagosomal rupture. This allows escape of phagosomal contents into the cytosol, where they access the endogenous major histocompatibility complex class I antigen processing pathway. The activity of DNGR-1 maps to its signaling domain, which activates SYK and NADPH oxidase to cause phagosomal damage even when spliced into a heterologous receptor and expressed in heterologous cells. Our data reveal the existence of innate immune receptors that couple ligand binding to endocytic vesicle damage to permit MHC class I antigen presentation of exogenous antigens and to regulate adaptive immunity.
CitationCanton J, Blees H, Henry CM, Buck MD, Schulz O, Rogers NC, et al. The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens. Nat Immunol. 2020.
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