title: Antigen translocation machineries in adaptive immunity and viral immune evasion.
abstract: Protein homeostasis results in a steady supply of peptides, which are further degraded to fuel protein synthesis or metabolic needs of the cell. In higher vertebrates, a small fraction of the resulting peptidome, however, is translocated into the endoplasmic reticulum by the transporter associated with antigen processing (TAP). Antigenic peptides are guided to major histocompatibility complex class I (MHC I) molecules and are finally displayed on the cell surface, where they mount an adaptive immune response against viral infected or malignantly transformed cells. Here, we review the structural organization and the molecular mechanism of this specialized antigen translocon. We discuss how the ATP-binding cassette (ABC) transporter TAP communicates and cooperates within the multi-component peptide loading machinery, mediating the proper assembly and editing of kinetically stable peptide/MHC I complexes. In light of its important role within the MHC I antigen processing pathway, TAP is a prime target for viral immune evasion strategies, and we summarize how this antigen translocation machinery is sabotaged by viral factors. Finally, we compare TAP with other ABC systems that facilitate peptide translocation.
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany.
authors.forename: Peter U
authors.initials: PU
authors.lastname: Mayerhofer
authors.affiliation: Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany; Cluster of Excellence Macromolecular Complexes, Goethe University Frankfurt, Max-von-Laue-Strasse 9, 60438 Frankfurt am Main, Germany. Electronic address: tampe@em.uni-frankfurt.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D014780:Viruses / Q000276:immunology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I
keywords: antigen presentation; membrane protein; peptide transport; peptide-loading complex; viral immune evasion