Regulation of CD1a Surface Expression and Antigen Presentation by Invariant Chain and Lipid Rafts1

Regulation of CD1a Surface Expression and Antigen Presentation by Invariant Chain and Lipid Rafts1
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DOI:
10.4049/jimmunol.180.2.980
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发表时间:
2008-01
期刊:
The Journal of Immunology
影响因子:
--
通讯作者:
I. Sloma;M. Zilber;T. Vasselon;N. Setterblad;M. Cavallari;L. Mori;G. De Libero;D. Charron;N. Mooney;C. Gélin
I. Sloma;M. Zilber;T. Vasselon;N. Setterblad;M. Cavallari;L. Mori;G. De Libero;D. Charron;N. Mooney;C. Gélin
中科院分区:
其他
文献类型:
--
作者:
I. Sloma;M. Zilber;T. Vasselon;N. Setterblad;M. Cavallari;L. Mori;G. De Libero;D. Charron;N. Mooney;C. Gélin

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在未成熟树突状细胞(DC)中,CD 1a几乎仅在细胞表面表达,并且其膜组织知之甚少。在这项研究中,我们报告,MHC II类,不变链(Ii),和CD 9分子与CD 1a在未成熟的DC共免疫沉淀,和CD 1a/Ii共定位是依赖于脂筏的完整性。在HeLa-CIITA细胞中,CD 1a表达导致Ii向细胞表面的运输增加,证实了这种关联的相关性。此外,Ii在DC中的沉默诱导质膜上显著的CD 1a积累,而总的CD 1a表达保持与对照细胞相似。这些数据表明,CD 1a的再循环是由与Ii的协会促进。CD 1a在脂筏中的定位具有功能相关性,如筏破坏后CD 1a限制性呈递的抑制所证明的。总的来说,这些发现确定Ii和脂筏作为未成熟DC表面上的CD 1a组织及其作为Ag呈递分子的免疫功能的关键调节剂。
In immature dendritic cells (DCs), CD1a is almost exclusively expressed at the cell surface and its membrane organization is poorly understood. In this study, we report that MHC class II, invariant chain (Ii), and CD9 molecules are coimmunoprecipitated with CD1a in immature DCs, and that CD1a/Ii colocalization is dependent on lipid raft integrity. In HeLa-CIITA cells CD1a expression leads to increased Ii trafficking to the cell surface, confirming the relevance of this association. Furthermore, silencing of Ii in DCs induces significant CD1a accumulation on the plasma membrane whereas the total CD1a expression remains similar to that of control cells. These data suggest that CD1a recycling is facilitated by the association with the Ii. The CD1a localization in lipid rafts has functional relevance as demonstrated by inhibition of CD1a-restricted presentation following raft disruption. Overall, these findings identify Ii and lipid rafts as key regulators of CD1a organization on the surface of immature DCs and of its immunological function as Ag-presenting molecule.