[HTML][HTML] The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

S Zelenay, AM Keller, PG Whitney… - The Journal of …, 2012 - Am Soc Clin Investig
S Zelenay, AM Keller, PG Whitney, BU Schraml, S Deddouche, NC Rogers, O Schulz
The Journal of clinical investigation, 2012Am Soc Clin Investig
DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs
against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell
recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by
dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment,
favoring cross-presentation to CD8+ T cells. DNGR-1 regulated cross-priming in non-
infectious settings such as immunization with antigen-bearing dead cells, as well as in …
DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8+ T cells. DNGR-1 regulated cross-priming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination.
The Journal of Clinical Investigation