HIV-1 infection leads to increased HLA-E expression resulting in impaired function of natural killer cells

Antivir Ther. 2005;10(1):95-107. doi: 10.1177/135965350501000107.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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 / genetics*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • HLA Antigens / genetics*
  • HLA Antigens / metabolism*
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • In Vitro Techniques
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • 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

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • Epitopes
  • HIV Core Protein p24
  • HLA Antigens
  • Histocompatibility Antigens Class I
  • Lectins, C-Type
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily D
  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • TAP1 protein, human
  • TAP2 protein, human
  • DNA