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

2025/10/17 by Pi, Ruoxi, Zhao, Nancy Q, Bien, Allison J +6
Immunology and Microbiology · #610 Medicine &amp #Biological sciences #FOS: Biological sciences #FOS: Clinical medicine #FOS: Natural sciences #HIV Research and Treatment #Immune Cell Function and Interaction #Immunity #Immunology #Natural sciences #Reproductive System and Pregnancy #health

paper · doi:10.5167/uzh-280930

openalex publication_date 2025/10/17 · openalex created_date 2025/12/11 · openalex updated_date 2026/07/28

Abstract

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 . 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.

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