New insights into the structure of the MHC class I peptide-loading complex and mechanisms of TAP inhibition by viral immune evasion proteins. (September 2019)

• Record Type: Journal Article
• Authors: Praest, Patrique; Liaci, A. Manuel; Förster, Friedrich; Wiertz, Emmanuel J.H.J.
• Is Part Of: Molecular immunology. Volume 113(2019:Sep.)
• Page Start: 103
• Page End: 114
• Publication Date: 2019-09
• Subjects: MHC class I -- TAP -- Antigen presentation -- Viral immune evasion -- Peptide loading complex -- Herpesvirus; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.03.020
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: The molecular composition of the MHC I peptide loading complex is delineated. Important structural aspects of the TAP peptide transport cycle are summarized. Novel data on the viral TAP inhibitors ICP47 and CPXV012 are discussed. Abstract: Several hundred million years of co-evolution of vertebrates and invading pathogens have shaped the adaptive immune system to fight back the unwanted invaders through highly sophisticated defense mechanisms. Herpesviruses manage to dodge this immune response by hampering one of the central hinges of human adaptive immunity, the major histocompatibility complex (MHC) class I antigen presentation pathway. One of the bottlenecks of this pathway is the loading of pathogen-derived peptides onto MHC-I molecules in the endoplasmic reticulum (ER). This task is accomplished by the MHC class I peptide-loading complex (PLC), of which the transporter associated with antigen-processing (TAP) is a central component. In this review, we summarize recent structural and functional insights into the molecular architecture of the PLC, how TAP accomplishes the transport of peptides across the ER membrane, and how herpes- and poxviruses inhibit TAP-mediated peptide translocation and subsequent antigen presentation.