The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement
The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement
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DOI：
10.1182/blood-2008-05-155176
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发表时间：
2008-10-15
期刊：
影响因子：
20.3
通讯作者：
Lahoud, Mireille H.
中科院分区：
文献类型：
--
作者：
Caminschi, Irina;Proietto, Anna I.;Lahoud, Mireille H.
通过小鼠 DC 亚型的基因表达谱鉴定了一种新型树突状细胞 (DC) 限制性分子 Clec9A。根据序列相似性，鉴定出人类直向同源物。 Clec9A 编码具有单个胞外 C 型凝集素结构域的 II 型膜蛋白。小鼠 Clec9A 和人 CLEC9A 都被克隆和表达，并产生了针对每种的单克隆抗体 (mAb)。表面染色显示，Clec9A 对小鼠 DC 具有选择性，并且仅限于 CD8(+) 常规 DC 和浆细胞样 DC 亚型。人类血液 DC 的一个子集也表达 CLEC9A。向小鼠单次注射针对 DC 的抗原 (Ag) 的 Clec9A 单克隆抗体，在没有添加佐剂或危险信号的情况下，即使在缺乏 Toll 样受体信号通路的小鼠中，也会产生显着增强的抗体反应。这种靶向还增强了 CD4 和 CD8 T 细胞反应。因此，Clec9A 可作为区分小鼠和人类 DC 亚型的新标记。此外，即使在没有佐剂的情况下，用 Clec9A 抗体将 Ag 靶向 DC 也是提高疫苗效率的一种有前途的策略。
A novel dendritic cell (DC)-restricted molecule, Clec9A, was identified by gene expression profiling of mouse DC subtypes. Based on sequence similarity, a human ortholog was identified. Clec9A encodes a type II membrane protein with a single extracellular C-type lectin domain. Both the mouse Clec9A and human CLEC9A were cloned and expressed, and monoclonal antibodies (mAbs) against each were generated. Surface staining revealed that Clec9A was selective for mouse DCs and was restricted to the CD8(+) conventional DC and plasmacytoid DC subtypes. A subset of human blood DCs also expressed CLEC9A. A single injection of mice with a mAb against Clec9A, which targets antigens (Ags) to the DCs, produced a striking enhancement of antibody responses in the absence of added adjuvants or danger signals, even in mice lacking Toll-like receptor signaling pathways. Such targeting also enhanced CD4 and CD8 T-cell responses. Thus, Clec9A serves as a new marker to distinguish subtypes of both mouse and human DCs. Furthermore, targeting Ags to DCs with antibodies to Clec9A is a promising strategy to enhance the efficiency of vaccines, even in the absence of adjuvants.