HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells |
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Authors: | Nattermann Jacob Nischalke Hans Dieter Hofmeister Valesko Kupfer Bernd Ahlenstiel Golo Feldmann Georg Rockstroh Jiirgen Weiss Elisabeth H Sauerbruch Tilman Spengler Ulrich |
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Affiliation: | Department of Internal Medicine I, Rheinische Friedrich-Wilhelms-Universit?t, Bonn, Germany. Jacob.Nattermann@ukb.uni-bonn.de |
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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. |
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