期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 122, 期 5, 页码 1615-1627出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI60644
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资金
- Cancer Research UK
- Fondation Bettencourt-Schueller. S. Zelenay
- EMBO
- Marie Curie Intra-European Fellowship
- National Health and Medical Research Council of Australia
- Spanish Ministry of Innovation and Science
- Cancer Research UK [15689] Funding Source: researchfish
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.
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