1-s2.0-S1044532323000179-main.pdf (1.73 MB)
DNGR-1-mediated cross-presentation of dead cell-associated antigens.
journal contributionposted on 2023-02-13, 11:00 authored by Conor M Henry, Carlos A Castellanos, Caetano Reis E Sousa
Conventional dendritic cells type 1 (cDC1) are critical for inducing protective CD8+ T cell responses to tumour and viral antigens. In many instances, cDC1 access those antigens in the form of material internalised from dying tumour or virally-infected cells. How cDC1 extract dead cell-associated antigens and cross-present them in the form of peptides bound to MHC class I molecules to CD8+ T cells remains unclear. Here we review the biology of dendritic cell natural killer group receptor-1 (DNGR-1; also known as CLEC9A), a C-type lectin receptor highly expressed on cDC1 that plays a key role in this process. We highlight recent advances that support a function for DNGR-1 signalling in promoting inducible rupture of phagocytic or endocytic compartments containing dead cell debris, thereby making dead cell-associated antigens accessible to the endogenous MHC class I processing and presentation machinery of cDC1. We further review how DNGR-1 detects dead cells, as well as the functions of the receptor in anti-viral and anti-tumour immunity. Finally, we highlight how the study of DNGR-1 has opened new perspectives into cross-presentation, some of which may have applications in immunotherapy of cancer and vaccination against viral diseases.
Crick (Grant ID: CC2090, Grant title: Reis e Sousa CC2090) Wellcome Trust (Grant ID: 223136/Z/21/Z, Grant title: WT 223136/Z/21/Z)