Mannosylation of virus-like particles enhances internalization by antigen presenting cells.
Mannosylation of virus-like particles enhances internalization by antigen presenting cells.
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DOI：
10.1371/journal.pone.0104523
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ward VK
中科院分区：
文献类型：
--
作者：
Al-Barwani F;Young SL;Baird MA;Larsen DS;Ward VK
抗原提呈细胞对多肽的内化对于启动获得性免疫反应至关重要。甘露糖化已被证明通过甘露糖受体增强抗原摄取，从而改善免疫反应。在这项研究中，我们测试了兔出血症病毒(RHDV)蛋白基病毒样颗粒(VLP)表面甘露糖化对小鼠和人类抗原提呈细胞摄取的影响。合成了一个单甘露糖苷和一个新的甘露糖苷，并成功地将其连接到RHDV VLP衣壳蛋白上，在每个病毒颗粒的表面提供了大约270个甘露糖基。与甘露糖苷或甘露糖苷偶联的VLP可显著增强小鼠树突状细胞、巨噬细胞和B细胞以及人树突状细胞和巨噬细胞的结合和内化。这种摄取被甘露聚糖作为甘露糖特异性摄取的特异性抑制剂所抑制，这表明VLP的甘露糖化针对的是基于甘露糖受体的摄取。与基于甘露糖受体的摄取一致，观察到RHDV VLP的细胞内加工的部分重定向，证实了VLP的甘露糖化既提供了相关抗原的增强摄取，也提供了相关抗原的修饰加工。
Internalization of peptides by antigen presenting cells is crucial for the initiation of the adaptive immune response. Mannosylation has been demonstrated to enhance antigen uptake through mannose receptors, leading to improved immune responses. In this study we test the effect of surface mannosylation of protein-based virus-like particles (VLP) derived from Rabbit hemorrhagic disease virus (RHDV) on uptake by murine and human antigen presenting cells. A monomannoside and a novel dimannoside were synthesized and successfully conjugated to RHDV VLP capsid protein, providing approximately 270 mannose groups on the surface of each virus particle. VLP conjugated to the mannoside or dimannoside exhibited significantly enhanced binding and internalization by murine dendritic cells, macrophages and B cells as well as human dendritic cells and macrophages. This uptake was inhibited by the inclusion of mannan as a specific inhibitor of mannose specific uptake, demonstrating that mannosylation of VLP targets mannose receptor-based uptake. Consistent with mannose receptor-based uptake, partial retargeting of the intracellular processing of RHDV VLP was observed, confirming that mannosylation of VLP provides both enhanced uptake and modified processing of associated antigens.
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