Open AccessThe receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens
Author(s) -
Johnathan Canton,
H. Blees,
Conor M. Henry,
Michael D. Buck,
Oliver Schulz,
Neil C. Rogers,
Eleanor Childs,
Santiago Zelenay,
Hefin Rhys,
Marie-Charlotte Domart,
Lucy Collinson,
Andrés Alloatti,
Cara J. Ellison,
Sebastián Amigorena,
Venizelos Papayannopoulos,
David Thomas,
Felix Randow,
Caetano Reis e Sousa
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-00824-x
Subject(s) - cross presentation , microbiology and biotechnology , biology , antigen presentation , mhc class i , antigen , antigen processing , acquired immune system , endocytic cycle , antigen presenting cell , t cell receptor , major histocompatibility complex , cd8 , receptor , t cell , immune system , immunology , endocytosis , biochemistry
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.