The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells
The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells
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DOI：
10.4049/jimmunol.168.5.2118
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发表时间：
2002-03-01
影响因子：
4.4
通讯作者：
van Kooyk, Y
中科院分区：
文献类型：
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作者：
Engering, A;Geijtenbeek, TBH;van Kooyk, Y
树突状细胞 (DC) 捕获外周组织中的 Ag 或病毒，将其转运至淋巴器官，诱导细胞 T 细胞反应。最近，鉴定出一种 DC 特异性 C 型凝集素，即 DC 特异性 ICAM 捕获非整合素 (DC-SIGN)，它作为细胞粘附受体介导 DC 迁移和 T 细胞激活。 DC-SIGN 还充当 HIV-1R，捕获 HIVgp120 并促进 DC 诱导的 T 细胞的 HIV 传播。 DC-SIGN 细胞质尾部的内化基序暗示了 DC-SIGN 作为内吞受体的功能。在这项研究中，我们证明在 DC 上，DC-SIGN 在与可溶性配体结合后迅速内化。突变细胞质尾部的假定内化基序会减少配体诱导的内化。使用比率荧光成像和电子显微镜的详细分析表明，DC-SIGN-配体复合物靶向晚期内体/溶酶体。此外，DC-SIGN内化的配体被有效加工并呈递给CD4(+) T细胞。 C 型凝集素在 DC 上原位表达的独特模式及其不重叠的 Ag 识别谱暗示了这些受体的选择性功能，使 DC 能够识别多种 Ag 并处理它们以诱导 T 细胞激活。这些数据表明粘附受体 DC-SIGN 作为一种有效的 DC 特异性 Ag 受体的新功能，可用作诱导病毒和抗肿瘤免疫的靶标。
Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-Ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4(+) T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.