Regulation of HLAclass I surface expression requires CD99 and p230/golgin-245 interaction
Regulation of HLAclass I surface expression requires CD99 and p230/golgin-245 interaction
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DOI：
10.1182/blood-2008-02-137745
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发表时间：
2009-01-08
期刊：
影响因子：
20.3
通讯作者：
Bernard, Ghislaine
中科院分区：
文献类型：
--
作者：
Bremond, Aurore;Meynet, Ophelie;Bernard, Ghislaine
通过在细胞表面呈递抗原肽，人类白细胞抗原（HLA）I类分子对于免疫防御至关重要。它们的表面密度在很大程度上决定了CD 8（+）T细胞依赖性免疫反应的水平;它们的丢失是免疫逃逸的主要机制。因此，强大的过程应该调节它们的表面表达。在这里，我们记录了CD 99介导HLA I类调节的机制。IFN-γ上调HLA I类需要CD 99。在跨高尔基体网络（TGN）中，直到细胞表面，CD 99和HLA I类通过其跨膜结构域物理关联。CD 99还结合p230/golgin-245，p230/golgin-245是一种卷曲螺旋蛋白，其在TGN的胞质溶胶和芽/囊泡之间穿梭，并且在运输运输囊泡中起着重要作用。p230/golgin-245通过其Golgin-97、RanBP 1、IMh 1 p、P230（GRIP）结构域锚定在TGN膜内，并且其过表达导致HLA I类分子的表面和细胞内下调。（血。2009;113：347-357）
By presenting antigenic peptides on the cell surface, human leukocyte antigen (HLA) class I molecules are critical for immune defense. Their surface density determines, to a large extent, the level of CD8(+) T cell-dependent immune reactions; their loss is a major mechanism of immune escape. Therefore, powerful processes should regulate their surface expression. Here we document the mechanisms used by CD99 to mediate HLA class I modulation. Up-regulation of HLA class I by IFN-gamma requires CD99. In the trans Golgi network (TGN), and up to the cell surface, CD99 and HLA class I are physically associated via their transmembrane domain. CD99 also binds p230/golgin-245, a coiled-coil protein that recycles between the cytosol and buds/vesicles of the TGN and which plays a fundamental role in trafficking transport vesicles. p230/golgin-245 is anchored within TGN membranes via its Golgin-97, RanBP1, IMh1p, P230 (GRIP) domain and the overexpression of which leads to surface and intracellular down-modulation of HLA class I molecules. (Blood. 2009;113:347-357)