The transporter associated with antigen processing (TAP) is active in a post-ER compartment
The transporter associated with antigen processing (TAP) is active in a post-ER compartment
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DOI：
10.1242/jcs.060632
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发表时间：
2010-12-15
影响因子：
4
通讯作者：
Springer, Sebastian
中科院分区：
文献类型：
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作者：
Ghanem, Esther;Fritzsche, Susanne;Springer, Sebastian
在主要组织相容性复合体(MHC)I类分子向T细胞递呈细胞内抗原的过程中，胞浆多肽移位到内质网(ER)的管腔中是至关重要的一步。它是由与抗原处理相关的转运蛋白(TAP)介导的，TAP蛋白与多肽受体MHC I类分子结合形成MHC I类多肽负载复合体(PLC)。我们调查了TAP是否存在并活跃在内质网下游的隔室。在荧光显微镜下，我们发现TAP定位于成纤维细胞和淋巴细胞的ERGIC(内质网高尔基体中间区)和高尔基体。使用体外囊泡形成实验，我们发现COPII囊泡携带分泌货物离开内质网，包含与MHC I类分子相关的功能TAP。再加上我们之前对多肽受体I类分子的内质网后定位的工作，我们的结果表明，在多肽负载复合体的背景下，多肽负载到I类分子上可以发生在内质网之外。
The translocation of cytosolic peptides into the lumen of the endoplasmic reticulum (ER) is a crucial step in the presentation of intracellular antigen to T cells by major histocompatibility complex (MHC) class I molecules. It is mediated by the transporter associated with antigen processing (TAP) protein, which binds to peptide-receptive MHC class I molecules to form the MHC class I peptide-loading complex (PLC). We investigated whether TAP is present and active in compartments downstream of the ER. By fluorescence microscopy, we found that TAP is localized to the ERGIC (ER-Golgi intermediate compartment) and the Golgi of both fibroblasts and lymphocytes. Using an in vitro vesicle formation assay, we show that COPII vesicles, which carry secretory cargo out of the ER, contain functional TAP that is associated with MHC class I molecules. Together with our previous work on post-ER localization of peptide-receptive class I molecules, our results suggest that loading of peptides onto class I molecules in the context of the peptide-loading complex can occur outside the ER.