The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments.
The dendritic cell receptor for endocytosis, DEC-205, can recycle and enhance antigen presentation via major histocompatibility complex class II-positive lysosomal compartments.
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DOI：
10.1083/jcb.151.3.673
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发表时间：
2000-10-30
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
--
作者：
Mahnke K;Guo M;Lee S;Sepulveda H;Swain SL;Nussenzweig M;Steinman RM
许多内吞作用受体通过早期内体循环进出细胞。我们现在在树突状细胞中发现，DEC-205多凝集素受体靶向富含主要组织相容性复合物II类（MHC II）产物的晚期内体或溶酶体，而同源巨噬细胞甘露糖受体（MMR），正如预期的那样，存在于更外周的内体中。为了分析这一发现，将 DEC-205 和 MMR 的胞质尾部融合到 CD16 Fcγ 受体的外部结构域，并在稳定的 L 细胞转染子中进行研究。这两个胞质结构域各自介导人免疫球蛋白 (Ig)G 的快速摄取，然后将完整的 CD16 再循环到细胞表面。然而，DEC-205 尾部通过 MHC II 阳性晚期内体/溶酶体液泡回收 CD16，并且还介导抗原呈递增加 100 倍。晚期内体靶向机制发生在不存在人 IgG 的情况下，涉及两个功能区域：具有用于摄取的包被凹坑序列的近膜区域，以及具有 EDE 三联体的远端区域，用于不寻常的更深靶向。因此，DEC-205胞质结构域介导了受体介导的内吞作用的新途径，该途径需要通过晚期内体进行有效回收，并大大提高抗原呈递给CD4+ T细胞的效率。
Many receptors for endocytosis recycle into and out of cells through early endosomes. We now find in dendritic cells that the DEC-205 multilectin receptor targets late endosomes or lysosomes rich in major histocompatibility complex class II (MHC II) products, whereas the homologous macrophage mannose receptor (MMR), as expected, is found in more peripheral endosomes. To analyze this finding, the cytosolic tails of DEC-205 and MMR were fused to the external domain of the CD16 Fcγ receptor and studied in stable L cell transfectants. The two cytosolic domains each mediated rapid uptake of human immunoglobulin (Ig)G followed by recycling of intact CD16 to the cell surface. However, the DEC-205 tail recycled the CD16 through MHC II–positive late endosomal/lysosomal vacuoles and also mediated a 100-fold increase in antigen presentation. The mechanism of late endosomal targeting, which occurred in the absence of human IgG, involved two functional regions: a membrane-proximal region with a coated pit sequence for uptake, and a distal region with an EDE triad for the unusual deeper targeting. Therefore, the DEC-205 cytosolic domain mediates a new pathway of receptor-mediated endocytosis that entails efficient recycling through late endosomes and a greatly enhanced efficiency of antigen presentation to CD4+ T cells.
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DOI：
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发表时间：
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期刊：
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影响因子：
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发表时间：
1990-12-01
期刊：
The Journal of experimental medicine
影响因子：
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