Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules.

Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group 1 CD1 molecules.
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DOI:
10.1002/eji.200738102
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发表时间:
2008-08
影响因子:
5.4
通讯作者:
Blumberg, Richard S.
Blumberg, Richard S.
中科院分区:
医学3区
文献类型:
--
作者:
Kaser, Arthur;Hava, David L.;Dougan, Stephanie K.;Chen, Zhangguo;Zeissig, Sebastian;Brenner, Michael B.;Blumberg, Richard S.

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脂质抗原通过非多态性MHC I类相关的CD1分子呈递给T细胞。微粒体甘油三酯转移蛋白(MTP)是一种内质网(ER)驻留伴侣,已被证明脂化组2 CD 1分子CD 1d,从而调节其功能。我们现在报告,MTP还调节第1组CD1分子CD1a,CD1b和CD1c的功能。MTP在单核细胞衍生的树突状细胞和淋巴母细胞样B细胞系转染组1 CD 1的药理学抑制导致内源性自身脂质抗原呈递到几个CD 1限制性T细胞系的大幅减少。在CD1c转染的HeLa细胞中沉默MTP表达同样导致自身反应性降低。出乎意料的是,抑制ER驻留MTP,这是由共聚焦显微镜证实,也显着降低了介绍外源性,内体加载,分枝杆菌脂质抗原的CD1a和CD1c的T细胞。因此,这些研究表明,MTP,尽管其ER定位,调节内源性以及外源性脂质抗原呈递,并建议广泛的作用,MTP在CD1抗原呈递的调节。
Lipid antigens are presented to T cells by the non-polymorphic MHC class I-related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)-resident chaperone that has been shown to lipidate the group 2 CD1 molecule CD1d and thus to regulate its function. We now report that MTP also regulates the function of group 1 CD1 molecules CD1a, CD1b, and CD1c. Pharmacological inhibition of MTP in monocyte-derived dendritic cells and lymphoblastoid B cell lines transfected with group 1 CD1 resulted in a substantial decrease in endogenous self lipid antigen presentation to several CD1-restricted T cell lines. Silencing MTP expression in CD1c-transfected HeLa cells similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER-resident MTP, which was confirmed by confocal microscopy, also markedly decreased presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation.
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