英国弗朗西斯·克里克研究所Caetano Reis e Sousa小组取得一项新突破。他们的研究发现受体DNGR-1诱导的吞噬体破裂信号促进了与死细胞相关的抗原交叉呈递。相关论文于2020年12月21号发表于国际学术期刊《自然-免疫学》杂志。

研究人员发现DNGR-1是XP专一性受体，在与配体结合后诱发促进吞噬体破裂的信号。这有利于吞噬体内容物逃逸到细胞质中，在细胞质内它们经历了内源性I类主要组织相容性抗原复合物加工途径。DNGR-1的活性映射到其信号结构域，即使将其剪接成异源受体并在异源细胞中表达，它也会激活SYK和NADPH氧化酶从而完成对吞噬体的破坏。该研究数据揭示了先天性免疫受体的存在，该受体与配体结合导致内吞小泡破裂，从而允许MHC I类抗原呈递外源抗原并调节适应性免疫。

研究人员表示，常规1型树突状细胞（cDC1）负责将许多病毒和肿瘤抗原交叉呈递至CD8⁺ T细胞。DNGR-1（也称为CLEC9A）高表达可用于分离小鼠和人体中的cDC1细胞，DNGR-1是一种结合死细胞碎片并促进细胞碎片相关抗原XP的受体。

附：英文原文

Title: The receptor DNGR-1 signals for phagosomal rupture to promote cross-presentation of dead-cell-associated antigens

Author: Johnathan Canton, Hanna Blees, Conor M. Henry, Michael D. Buck, Oliver Schulz, Neil C. Rogers, Eleanor Childs, Santiago Zelenay, Hefin Rhys, Marie-Charlotte Domart, Lucy Collinson, Andres Alloatti, Cara J. Ellison, Sebastian Amigorena, Venizelos Papayannopoulos, David C. Thomas, Felix Randow, Caetano Reis e Sousa

Issue&Volume: 2020-12-21

Abstract: 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. 

DOI: 10.1038/s41590-020-00824-x

Source: https://www.nature.com/articles/s41590-020-00824-x