Dependence of the localization and function of the human cytomegalovirus protein US6 on the transporter associated with antigen processing.
Human cytomegalovirus protein US6 inhibits the transporter associated with antigen processing (TAP), which transports peptides into the endoplasmic reticulum (ER) for binding to major histocompatibility complex (MHC) class I molecules. We demonstrate that, in TAP-deficient cells, US6 is retained in the ER and binds to calnexin, but does not inhibit cell-surface expression of HLA-A201, an MHC class I allele that binds to peptides whose import into the ER is TAP-independent. Furthermore, in TAP-positive cells, US6 reduces the cell-surface expression of HLA-B2705, an MHC class I allele that is dependent on TAP for peptide binding, to a greater extent than that of HLA-A201. These data demonstrate that US6 has differential effects on the cell-surface expression of MHC class I alleles and are consistent with TAP being the sole inhibitory target of US6 in the MHC class I antigen-presentation pathway.
Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Garstang Building, University of Leeds, Leeds LS2 9JT, UK.
Gillian E
GE
Dugan
Eric W
EW
Hewitt
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D017951:Antigen Presentation; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D015234:HLA-A Antigens; D016601:RNA-Binding Proteins; C432877:US6 protein, Human cytomegalovirus; D014764:Viral Proteins; C477327:transporter associated with antigen processing (TAP)