The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens - Archive ouverte HAL Access content directly
Journal Articles Nature Immunology Year : 2021

The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

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Michael Buck
Neil Rogers
Lucy Collinson

Abstract

Type 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.

Dates and versions

hal-03877502 , version 1 (29-11-2022)

Identifiers

Cite

Johnathan Canton, Hanna Blees, Conor Henry, Michael Buck, Oliver Schulz, et al.. The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens. Nature Immunology, 2021, 22 (2), pp.140-153. ⟨10.1038/s41590-020-00824-x⟩. ⟨hal-03877502⟩
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