MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation
MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation
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DOI：
10.1073/pnas.0708874105
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发表时间：
2008-03-04
影响因子：
11.1
通讯作者：
Gatti, Evelina
中科院分区：
文献类型：
--
作者：
De Gassart, Aude;Camosseto, Voahirana;Gatti, Evelina
树突状细胞（DCs）对Toll样受体配体的应答通过稳定细胞表面MHCII分子而显著增强其抗原提呈能力。我们在这里证明，在人单核细胞来源的DC中，RING-CH泛素E3连接酶，膜相关RING-CH I（MARCH I），促进HLA-DR β链的泛素化。因此，在未活化的DC中，MARCH I诱导成熟HLA-DR复合物的表面内化，从而降低其稳定性和水平。我们进一步证明，成熟依赖的下调MARCH I是一个关键事件，在表面的LPS激活的DC的MHC II类上调。因此，MARCH I是HLA-DR运输的主要调节因子，其缺失有助于获得成熟人DC的有效免疫刺激特性。
In response to Toll-like receptor ligands, dendritic cells (DCs) dramatically enhance their antigen presentation capacity by stabilizing at the cell-surface MHC II molecules. We demonstrate here that, in human monocyte-derived DCs, the RING-CH ubiquitin E3 ligase, membrane-associated RING-CH I (MARCH I), promotes the ubiquitination of the HLA-DR beta-chain. Thus, in nonactivated DCs, MARCH I induces the surface internalization of mature HLA-DR complexes, therefore reducing their stability and levels. We further demonstrate that the maturation-dependent down-regulation of MARCH I is a key event in MHC class II up-regulation at the surface of LPS-activated DCs. MARCH I is, therefore, a major regulator of HLA-DR traffic, and its loss contributes to the acquisition of the potent immunostimulatory properties of mature human DCs.