The transporter associated with antigen processing: a key player in adaptive immunity
The transporter associated with antigen processing: a key player in adaptive immunity
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DOI：
10.1515/hsz-2014-0320
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发表时间：
2015-09-01
影响因子：
3.7
通讯作者：
Tampe, Robert
中科院分区：
文献类型：
--
作者：
Eggensperger, Sabine;Tampe, Robert
适应性免疫系统与复杂的抗原加工途径共同进化，以有效清除病毒感染和恶性转化。抗原肽主要通过蛋白酶体降解产生，并通过与抗原加工相关的转运蛋白（TAP）转运到内质网（ER）的内腔中。在ER中，肽被装载到由多亚基肽装载复合物（PLC）协调的主要组织相容性复合物I（MHC I）分子上。肽-MHC I复合物靶向细胞表面，用于将抗原呈递给细胞毒性T细胞，这最终导致病毒感染或恶性转化细胞的消除。在这里，我们回顾了MHC I介导的抗原处理的功能和结构组织的异源二聚体ATP结合盒（ABC）转运TAP 1/2的主要重点。我们讨论了最近的数据的抗原易位复合物的分子转运机制与其他ABC出口商的结构和生化信息。我们进一步总结了TAP如何为大分子PLC的组装提供支架，从而将肽易位与MHC I加载耦合。不同的病毒evasins的TAP抑制突出了TAP在适应性免疫中的重要作用。
The adaptive immune system co-evolved with sophisticated pathways of antigen processing for efficient clearance of viral infections and malignant transformation. Antigenic peptides are primarily generated by proteasomal degradation and translocated into the lumen of the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). In the ER, peptides are loaded onto major histocompatibility complex I (MHC I) molecules orchestrated by a multisubunit peptide-loading complex (PLC). Peptide-MHC I complexes are targeted to the cell surface for antigen presentation to cytotoxic T cells, which eventually leads to the elimination of virally infected or malignantly transformed cells. Here, we review MHC I mediated antigen processing with a primary focus on the function and structural organization of the heterodimeric ATP-binding cassette (ABC) transporter TAP1/2. We discuss recent data on the molecular transport mechanism of the antigen translocation complex with respect to structural and biochemical information of other ABC exporters. We further summarize how TAP provides a scaffold for the assembly of the macromolecular PLC, thereby coupling peptide translocation with MHC I loading. TAP inhibition by distinct viral evasins highlights the important role of TAP in adaptive immunity.