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
in En
| MEDLINE
| ID: mdl-33349708
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dendritic Cells
/
Phagosomes
/
Receptors, Immunologic
/
Receptors, Mitogen
/
T-Lymphocytes
/
Antigen Presentation
/
Lectins, C-Type
/
Cross-Priming
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2021
Type:
Article
Affiliation country:
United kingdom