The transporter associated with antigen processing: a key player in adaptive immunity

被引:68
作者
Eggensperger, Sabine [1 ]
Tampe, Robert [1 ,2 ]
机构
[1] Goethe Univ Frankfurt, Bioctr, Inst Biochem, D-60438 Frankfurt, Germany
[2] Goethe Univ Frankfurt, Bioctr, Cluster Excellence Macromol Complexes, D-60438 Frankfurt, Germany
关键词
ABC transporter; antigen processing; membrane proteins; molecular immunology; viral immune evasion; HERPES-SIMPLEX-VIRUS; MAJOR-HISTOCOMPATIBILITY-COMPLEX; CLASS-I MOLECULES; NUCLEOTIDE-BINDING DOMAIN; PEPTIDE-LOADING COMPLEX; ABC TRANSPORTER; ATP-BINDING; ENDOPLASMIC-RETICULUM; MULTIDRUG TRANSPORTER; CRYSTAL-STRUCTURE;
D O I
10.1515/hsz-2014-0320
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1059 / 1072
页数:14
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