title: HCMV glycoprotein US6 mediated inhibition of TAP does not affect HLA-E dependent protection of K-562 cells from NK cell lysis.
abstract: Human cytomegalovirus has evolved multiple strategies to interfere with immune recognition by the host. A variety of mechanisms affect antigen presentation by major histocompatibility complex class I molecules resulting in a reduced class I cell-surface expression. This downregulation is expected to trigger natural killer (NK) cytotoxicity, requiring counteraction by the virus to establish long-term infection. Here we describe that the human cytomegalovirus gpUS6 protein, which has been demonstrated to downregulate the expression of human leukocyte antigen (HLA) class I and the presentation of cytotoxic T lymphocyte epitopes by blocking transporter associated with antigen presentation (TAP function), does not affect the ability of HLA-E to inhibit NK cell mediated lysis of K-562 cells by interaction with CD94/NKG2A expressed on NK cells. Cell surface expression and function of HLA-E is not altered although gpUS6 inhibits TAP-dependent peptide transport by 95%. Moreover, HLA-E molecules presenting HLA class I signal sequence-derived peptides are functionally detectable on transfected TAP-deficient RMA-S cells.
authors.affiliation: Department Biologie II, Ludwig-Maximilians-Universität München, Anthropologie und Humangenetik, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ulbrecht
authors.forename: Valeska
authors.initials: V
authors.lastname: Hofmeister
authors.forename: Gülnihål
authors.initials: G
authors.lastname: Yüksekdag
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Ellwart
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
authors.forename: Frank
authors.initials: F
authors.lastname: Momburg
authors.forename: Silvia
authors.initials: S
authors.lastname: Martinozzi
authors.forename: Murielle
authors.initials: M
authors.lastname: Reboul
authors.forename: Marika
authors.initials: M
authors.lastname: Pla
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Weiss
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000096:biosynthesis / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014162:Transfection; D014764:Viral Proteins / Q000502:physiology*; D000097625:HLA-E Antigens
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D006680:HLA Antigens; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; C527057:Klrc1 protein, mouse; C497870:Klrd1 protein, mouse; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C432877:US6 protein, Human cytomegalovirus