Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, UK.
J Clin Invest. 2012 May;122(5):1615-27. doi: 10.1172/JCI60644. Epub 2012 Apr 16.
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.
DNGR-1（CLEC9A）是树突状细胞识别坏死细胞所必需的受体，可使其针对死细胞抗原交叉呈递 CTL 反应。目前尚不清楚 DNGR-1 如何将识别坏死细胞与交叉呈递联系起来。我们发现，DNGR-1 并不介导 DC 对坏死细胞的激活，而是将坏死细胞的货物转移到再循环内体隔室，有利于 CD8(+)T 细胞的交叉呈递。DNGR-1 在非感染性条件下（如用携带抗原的死细胞免疫）和高度免疫原性情况下（如感染单纯疱疹病毒 1 型）调节交叉呈递。这些结果表明，DNGR-1 是细胞相关抗原交叉呈递的专用受体。因此，我们的工作强调了交叉呈递在免疫中的重要性，并表明抗原性和佐剂性可以通过不同的先天免疫受体来解码。专门调节病毒感染细胞抗原性的受体的鉴定揭示了抗病毒免疫的决定因素，这可能是人类对感染和接种的反应基础。
