Functional and antigenic characterization of human, rhesus macaque, pigtailed macaque, and murine DC-SIGN
Functional and antigenic characterization of human, rhesus macaque, pigtailed macaque, and murine DC-SIGN
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DOI：
10.1128/jvi.75.21.10281-10289.2001
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发表时间：
2001-11-01
影响因子：
5.4
通讯作者：
Doms, RW
中科院分区：
文献类型：
--
作者：
Baribaud, FD;Pöhlmann, S;Doms, RW
DC-SIGN是一种具有C型凝集素结合结构域的II型膜蛋白，在体内粘膜树突状细胞（DC）和某些巨噬细胞上高度表达，与ICAM-3、ICAM-2以及人和猿免疫缺陷病毒（HIV和SIV）结合。DC-SIGN捕获的病毒可以呈递给T细胞，导致有效的病毒感染，这可能代表了病毒可以通过正常DC从粘膜组织运输到体内淋巴器官的机制。为了开发表征DC-SIGN的表达和体内功能所需的试剂，我们克隆、表达和分析了恒河猴、猪尾猕猴和鼠DC-SIGN，并制备了一组针对人DC-SIGN的单克隆抗体（MAbs）。恒河猴和小尾猕猴DC-SIGN蛋白与人DC-SIGN蛋白高度相似，并将HIV-1、HIV-2和SIV结合并传播至受体阳性细胞。相比之下，虽然能够结合病毒，但在测试条件下，鼠DC-SIGN不会将病毒传递给受体阳性细胞。因此，仅仅病毒与C型凝集素结合并不一定意味着会发生传播。鼠和猕猴DC-SIGN分子均结合ICAM-3。我们映射的16个单克隆抗体的面板的重复区域，凝集素结合结构域，和极端的DC-SIGN的C末端的决定因素。1株单克隆抗体对DC-SIGN具有特异性，与DC-SIGNR无交叉反应。大多数单克隆抗体与恒河猴和小尾猕猴DC-SIGN交叉反应，尽管没有识别鼠DC-SIGN。其中15种MAb识别DC上的DC-SIGN，其中重复区的MAb反应通常最强烈。我们得出结论，恒河猴和猪尾猕猴DC-SIGN蛋白在结构和功能上与人DC-SIGN相似，我们开发的试剂将使研究这种分子在体内的表达和功能成为可能。
DC-SIGN, a type II membrane protein with a C-type lectin binding domain that is highly expressed on mucosal dendritic cells (DCs) and certain macrophages in vivo, binds to ICAM-3, ICAM-2, and human and simian immunodeficiency viruses (HIV and SIV). Virus captured by DC-SIGN can be presented to T cells, resulting in efficient virus infection, perhaps representing a mechanism by which virus can be ferried via normal DC trafficking from mucosal tissues to lymphoid organs in vivo. To develop reagents needed to characterize the expression and in vivo functions of DC-SIGN, we cloned, expressed, and analyzed rhesus macaque, pigtailed macaque, and murine DC-SIGN and made a panel of monoclonal antibodies (MAbs) to human DC-SIGN. Rhesus and pigtailed macaque DC-SIGN proteins were highly similar to human DC-SIGN and bound and transmitted HIV type 1 (HIV-1), HIV-2, and SIV to receptor-positive cells. In contrast, while competent to bind virus, murine DC-SIGN did not transmit virus to receptor-positive cells under the conditions tested. Thus, mere binding of virus to a C-type lectin does not necessarily mean that transmission will occur. The murine and macaque DC-SIGN molecules all bound ICAM-3. We mapped the determinants recognized by a panel of 16 MAbs to the repeat region, the lectin binding domain, and the extreme C terminus of DC-SIGN. One MAb was specific for DC-SIGN, failing to cross-react with DC-SIGNR. Most MAbs crossreacted with rhesus and pigtailed macaque DC-SIGN, although none recognized murine DC-SIGN. Fifteen of the MAbs recognized DC-SIGN on DCs, with MAbs to the repeat region generally reacting most strongly. We conclude that rhesus and pigtailed macaque DC-SIGN proteins are structurally and functionally similar to human DC-SIGN and that the reagents that we have developed will make it possible to study the expression and function of this molecule in vivo.