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Mol Immunol. 2018 Mar 29. pii: S0161-5890(18)30099-3. doi: 10.1016/j.molimm.2018.03.020. [Epub ahead of print]

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

Author information

1
Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands.
2
Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584CH Utrecht, The Netherlands.
3
Department of Medical Microbiology, University Medical Center Utrecht, 3584CX Utrecht, The Netherlands. Electronic address: e.wiertz@umcutrecht.nl.

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.

KEYWORDS:

Antigen presentation; Herpesvirus; MHC class I; Peptide loading complex; TAP; Viral immune evasion

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