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Antivir Ther ; 10(1): 95-107, 2005.
Article in English | MEDLINE | ID: mdl-15751767

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.


Subject(s)
HIV Infections/genetics , HIV Infections/immunology , HLA Antigens/genetics , HLA Antigens/metabolism , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class I/metabolism , Killer Cells, Natural/immunology , ATP Binding Cassette Transporter, Subfamily B, Member 2 , ATP Binding Cassette Transporter, Subfamily B, Member 3 , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Amino Acid Sequence , Antigens, CD/metabolism , Base Sequence , CD4-Positive T-Lymphocytes/immunology , Case-Control Studies , Cytotoxicity, Immunologic , DNA/genetics , Epitopes/metabolism , HIV Core Protein p24/genetics , HIV Core Protein p24/metabolism , HIV Infections/virology , HIV-1/immunology , HIV-1/pathogenicity , Humans , In Vitro Techniques , K562 Cells , Lectins, C-Type/metabolism , Ligands , Molecular Sequence Data , NK Cell Lectin-Like Receptor Subfamily D , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Immunologic/metabolism , Receptors, Natural Killer Cell , Transfection , Up-Regulation , HLA-E Antigens
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