title: HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells.
abstract: HIV has evolved several strategies to evade recognition by the host immune system including down-regulation of major histocompatibility complex (MHC) class I molecules. However, reduced expression of MHC class I molecules may stimulate natural killer (NK) cell lysis in cells of haematopoietic lineage. Here, we describe how HIV counteracts stimulation of NK cells by stabilizing surface expression of the non-classical MHC class I molecule, HLA-E. We demonstrate enhanced expression of HLA-E on lymphocytes from HIV-infected patients and show that in vitro infection of lymphocytes with HIV results in up-regulation of HLA-E expression and reduced susceptibility to NK cell cytotoxicity. Using HLA-E transfected K-562 cells, we identified the well-known HIV T-cell epitope p24 aa14-22a as a ligand for HLA-E that stabilizes surface expression of HLA-E, favouring inhibition of NK cell cytotoxicity. These results propose HIV-mediated up-regulation of HLA-E expression as an additional evasion strategy targeting the antiviral activities of NK cells, which may contribute to the capability of the virus in establishing chronic infection.
authors.affiliation: Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany. Jacob.Nattermann@ukb.uni-bonn.de
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Nischalke
authors.forename: Valesko
authors.initials: V
authors.lastname: Hofmeister
authors.forename: Bernd
authors.initials: B
authors.lastname: Kupfer
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.forename: Georg
authors.initials: G
authors.lastname: Feldmann
authors.forename: Jiirgen
authors.initials: J
authors.lastname: Rockstroh
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Weiss
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D051920:NK Cell Lectin-Like Receptor Subfamily D; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D014162:Transfection; D015854:Up-Regulation; D000097625:HLA-E Antigens
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D004247:DNA; D000939:Epitopes; D016655:HIV Core Protein p24; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D051920:NK Cell Lectin-Like Receptor Subfamily D; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C073119:TAP1 protein, human; C071692:TAP2 protein, human