Developmental regulation of MHC class II transport in mouse dendritic cells
Developmental regulation of MHC class II transport in mouse dendritic cells
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DOI：
10.1038/42039
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发表时间：
1997-08-21
期刊：
影响因子：
64.8
通讯作者：
Mellman, I
中科院分区：
文献类型：
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作者：
Pierre, P;Turley, SJ;Mellman, I
树突状细胞(DC)具有启动一次和二次免疫反应的独特能力(1-3)。它们在周围组织中获得抗原，并迁移到淋巴器官，在那里它们将经过处理的多肽提供给T细胞。因此，DC必须以不同的功能状态存在，这一观点得到了观察的支持，即它们在成熟时下调内吞作用，上调II类主要组织相容性复合体(MHC)的表面分子(4-7)。在此，我们通过在体外和原位重建小鼠DC的终末分化来研究DC成熟的特征。我们发现，早期树突状细胞与周围组织中发现的树突状细胞相对应，表现出一种表型，即大多数II类分子位于细胞内并定位于溶酶体。成熟后，这些细胞会产生一种新的中间表型，在这种表型中，细胞内的II类分子存在于周围的非溶酶体小泡中，类似于B细胞中特殊的CIIV群体。然后，中间细胞分化为晚期DC，后者几乎所有的II类分子都表达在质膜上。这些II类分隔的变化伴随着NE IV II类分子在细胞内的运输和抗原提呈的显著变化。我们发现，尽管早期的DC不能在摄取后立即呈递抗原，但在成熟后，24-48小时后，先前内化的抗原就能有效地呈递。通过调节II类转运和分区，树突状细胞能够延迟抗原展示，这一特性对它们在免疫监视中的作用至关重要。
Dendritic cells (DCs) have the unique capacity to initiate primary and secondary immune responses(1-3). They acquire antigens in peripheral tissues and migrate to lymphoid organs where they present processed peptides to T cells. DCs must therefore exist in distinct functional states, an idea that is supported by observations that they downregulate endocytosis and upregulate surface molecules of the class II major histocompatibility complex (MHC) upon maturation(4-7). Here we investigate the features of DC maturation by reconstituting the terminal differentiation of mouse DCs in vitro and in situ. We find that early DCs, corresponding to those found in peripheral tissues, exhibit a phenotype in which most class II molecules are intracellular and localized to lysosomes. Upon maturation, these cells give rise to a new intermediate phenotype in which intracellular class II molecules are found in peripheral non-lysosomal vesicles, similar to the specialized CIIV population seen in B cells. The intermediate cells then differentiate into late DCs which express almost all of their class II molecules on the plasma membrane. These variations in class II compartmentalization are accompanied by dramatic alterations in the intracellular transport of the ne iv class II molecules and in antigen presentation. We found that although early DCs could not present antigen immediately after uptake, efficient presentation of the previously internalized antigen occurred after maturation, 24-48 hours later. By regulating class II transport and compartmentalization, DCs are able to delay antigen display, a property crucial to their role in immune surveillance.