Mature dendritic cells use endocytic receptors to capture and present antigens
Mature dendritic cells use endocytic receptors to capture and present antigens
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DOI：
10.1073/pnas.0910609107
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发表时间：
2010-03-02
影响因子：
11.1
通讯作者：
Delamarre, Lelia
中科院分区：
文献类型：
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作者：
Platt, Craig D.;Ma, Jessica K.;Delamarre, Lelia
树突状细胞（DC）对炎症刺激的反应是触发成熟过程，这是启动T淋巴细胞反应所需的终末分化程序。成熟的标志是内吞作用的下调，这被广泛认为限制了成熟DC捕获和呈递初始刺激后遇到的抗原的能力。我们发现，成熟的DC继续积累抗原，特别是通过受体介导的内吞作用和吞噬作用。内化的抗原通常被转运到晚期内体和溶酶体，装载到MHC II类分子（MHCII）上，然后有效地呈递给T细胞。尽管成熟导致MHCII从晚期内吞隔室中的一般消耗，但这种情况仍然发生，其中MHCII富集通常被认为是抗原加工和肽装载隔室所需的特征。内化的抗原也可以交叉呈递在MHC I类分子上，相对于未成熟的DC，效率没有任何降低。因此，虽然成熟的DC显着下调其巨胞饮的能力，他们继续捕获，处理，并通过内吞受体内化的抗原，这表明他们可能会不断启动新遇到的抗原在感染过程中的反应。
In response to inflammatory stimuli, dendritic cells (DCs) trigger the process of maturation, a terminal differentiation program required to initiate T-lymphocyte responses. A hallmark of maturation is down-regulation of endocytosis, which is widely assumed to restrict the ability of mature DCs to capture and present antigens encountered after the initial stimulus. We found that mature DCs continue to accumulate antigens, especially by receptor-mediated endocytosis and phagocytosis. Internalized antigens are transported normally to late endosomes and lysosomes, loaded onto MHC class II molecules (MHCII), and then presented efficiently to T cells. This occurs despite the fact that maturation results in the general depletion of MHCII from late endocytic compartments, with MHCII enrichment being typically thought to be a required feature of antigen processing and peptide loading compartments. Internalized antigens can also be cross-presented on MHC class I molecules, without any reduction in efficiency relative to immature DCs. Thus, although mature DCs markedly down-regulate their capacity for macropinocytosis, they continue to capture, process, and present antigens internalized via endocytic receptors, suggesting that they may continuously initiate responses to newly encountered antigens during the course of an infection.