The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens.
Nat Immunol
; 22(2): 140-153, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33349708
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Fagossomos
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Receptores Imunológicos
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Receptores Mitogênicos
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Linfócitos T
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Apresentação de Antígeno
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Lectinas Tipo C
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Apresentação Cruzada
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article