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bioRxiv · 10.1101/2024.06.24.600449

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

Zhao, N. Q.·Pi, R.·Nguyen, D. N.·Ranganath, T.·Seiler, C.·Holmes, S.·Marson, A.·Blish, C. A.
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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 HIV-1-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 knockout the NKp30 ligand B7-H6, or the NKG2D ligands MICB or ULBP2 reduced NK cell responses to HIV-infected cells in some donors. In contrast, overexpression of NKp30 or NKG2D in NK cells enhanced their targeting of HIV-infected cells. Collectively, we identified receptor-ligand pairs including NKp30:B7-H6 and NKG2D:MICB/ULBP2 that contribute to NK cell recognition of HIV-infected cells.

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Zhao, N. Q., Pi, R., Nguyen, D. N., Ranganath, T., Seiler, C., Holmes, S., Marson, A., Blish, C. A.. 2024-06-27. NKp30 and NKG2D contribute to natural killer recognition of HIV-infected cells. https://doi.org/10.1101/2024.06.24.600449

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