Abstract
The ability of natural killer (NK) cells to kill virus-infected cells depends on the presence of ligands for activation receptors on the target cells. We found the presence of few, if any, NKp30 and NK46 ligands on T cell blasts infected with HIV, although NKp44 ligands were found on infected cells. HIV does induce the NKG2D ligands ULBP-1, -2, and -3. These ligands are involved in triggering NK cells to kill autologous HIV-infected cells, because interfering with the interaction between NKG2D, but not NKp46, on NK cells and its ligands on HIV-infected cells drastically reduced the lysis of infected cells. Interfering with the binding of the NK-cell coreceptors NTB-A and 2B4 to their ligands also decreased destruction by NK cells. The coreceptor ligands, NTB-A and CD48, were also found to be down-regulated during the course of HIV infection. Thus, ligands for NK-cell receptors are modulated during the course of HIV infection, which may greatly alter NK cells' ability to kill the infected cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antigens, CD / metabolism
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CD48 Antigen
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Cytotoxicity, Immunologic / immunology*
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GPI-Linked Proteins
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Gene Expression Regulation
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HIV Infections / immunology*
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HIV Infections / metabolism
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HIV Infections / pathology
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HIV Seropositivity
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HIV-1 / physiology*
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Humans
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Intercellular Signaling Peptides and Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / virology
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Ligands
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Membrane Glycoproteins / metabolism
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Membrane Proteins / metabolism
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 3
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Receptors, Cell Surface / metabolism
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Receptors, Natural Killer Cell
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1
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T-Lymphocytes / immunology
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T-Lymphocytes / virology*
Substances
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Antigens, CD
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CD244 protein, human
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CD48 Antigen
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CD48 protein, human
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GPI-Linked Proteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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KLRK1 protein, human
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Ligands
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Membrane Glycoproteins
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Membrane Proteins
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NCR3 protein, human
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 3
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Receptors, Cell Surface
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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SLAMF6 protein, human
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Signaling Lymphocytic Activation Molecule Family
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ULBP1 protein, human
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ULBP2 protein, human
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ULBP3 protein, human
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Signaling Lymphocytic Activation Molecule Family Member 1