Mahnke K, Guo M, Lee S, Sepulveda H, Swain S L, Nussenzweig M, Steinman R M
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.
J Cell Biol. 2000 Oct 30;151(3):673-84. doi: 10.1083/jcb.151.3.673.
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 Fcgamma 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.
许多用于内吞作用的受体通过早期内体在细胞内外循环。我们现在发现，在树突状细胞中，DEC-205多凝集素受体靶向富含主要组织相容性复合体II类（MHC II）产物的晚期内体或溶酶体，而同源的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的胞质尾部与CD16 Fcγ受体的胞外结构域融合，并在稳定的L细胞转染子中进行研究。这两个胞质结构域均介导人免疫球蛋白（Ig）G的快速摄取，随后完整的CD16循环至细胞表面。然而，DEC-205尾部通过MHC II阳性的晚期内体/溶酶体空泡循环CD16，并且还介导抗原呈递增加100倍。在没有人IgG的情况下发生的晚期内体靶向机制涉及两个功能区域：一个具有用于摄取的包被小窝序列的膜近端区域，以及一个具有用于异常更深靶向的EDE三联体的远端区域。因此，DEC-205胞质结构域介导了一种新的受体介导的内吞作用途径，该途径需要通过晚期内体进行高效循环，并大大提高了向CD4(+) T细胞呈递抗原的效率。
