NKp30 and NKG2D contribute to natural killer cell-mediated recognition of HIV-infected cells

Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autolo...

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Vydáno v:iScience Ročník 28; číslo 10; s. 113548
Hlavní autoři: Pi, Ruoxi, Zhao, Nancy Q., Bien, Allison J., Ranganath, Thanmayi, Seiler, Christof, Holmes, Susan, Marson, Alexander, Nguyen, David N., Blish, Catherine A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 17.10.2025
Elsevier
Témata:
Biological sciences
Immunity
Immunology
Natural sciences
Biological sciences
Immunology
Natural sciences
Immunity
ISSN:2589-0042, 2589-0042
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Shrnutí:Natural killer (NK) cells respond rapidly in early HIV-1 infection. HIV-1 prevention and control strategies harnessing NK cells could be enabled by mechanistic understanding of how NK cells recognize HIV-infected T cells. Here, we profiled the phenotype of human primary NK cells responsive to autologous newly HIV-infected CD4 T cells in vitro. We characterized the patterns of NK cell ligand expression on CD4 T cells at baseline and after infection with a panel of transmitted/founder HIV-1 strains to identify key receptor-ligand pairings. CRISPR editing of CD4 T cells to knock out the NKp30 ligand B7-H6, or the NKG2D ligand MICB reduced NK cell responses to HIV-infected cells in some donors. Blockade of NKp30 or NKG2D on NK cells compromised their specificity of killing HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB that contribute to NK cell recognition of HIV-infected cells. [Display omitted] •Ligands of NKp30 and NKG2D are upregulated on HIV-infected CD4 T cells•Ligand expression varies more between individuals than between viral strains•NKp30 and NKG2D facilitate HIV-specific cytotoxicity mediated by NK cells Natural sciences; Biological sciences; Immunology; Immunity
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ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2025.113548