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首页> 外文期刊>Nature >Developmental regulation of MHC class Ⅱ transport in mouse dendritic cells
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Developmental regulation of MHC class Ⅱ transport in mouse dendritic cells

机译：小鼠树突状细胞中MHCⅡ类转运的发育调控

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Dendritic cells (DCs) have the unique capacity to initiate primary and secondary immune responses. 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. 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 new 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.
机译：树突状细胞（DCs）具有启动初次和二次免疫反应的独特能力。它们在外周组织中获取抗原，然后迁移至淋巴器官，在此处它们将加工过的肽呈递给T细胞。因此，DC必须以不同的功能状态存在，这一观点得到了以下观察的支持：观察到DC在成熟时会下调内吞作用并上调Ⅱ类主要组织相容性复合物（MHC）的表面分子。在这里，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，与周围组织中发现的DC相对应的DC表现出一种表型，其中大多数Ⅱ类分子位于细胞内并位于溶酶体中。成熟后，这些细胞产生新的中间表型，其中在外周非溶酶体囊泡中发现了细胞内的Ⅱ类分子，类似于在B细胞中看到的特化CIIV群体。然后，中间细胞分化为晚期DC，其在质膜上表达几乎所有的Ⅱ类分子。 Ⅱ类区室化的这些变化伴随着新的Ⅱ类分子的细胞内转运和抗原呈递的急剧变化。我们发现，尽管早期的DC在摄取后不能立即呈递抗原，但在成熟后24-48小时后才有效呈递先前内在化的抗原。通过调节Ⅱ类转运和分隔，DC能够延迟抗原展示，这对它们在免疫监视中的作用至关重要。

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