NKp30 and NKG2D contribute to natural killer 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:bioRxiv
Hlavní autoři: Zhao, Nancy Q, Pi, Ruoxi, Nguyen, David N, Ranganath, Thanmayi, Seiler, Christof, Holmes, Susan, Marson, Alexander, Blish, Catherine A
Médium: Journal Article Paper
Jazyk:angličtina
Vydáno: United States Cold Spring Harbor Laboratory 27.06.2024
Vydání:1.1
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ISSN:2692-8205, 2692-8205
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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 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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Competing Interest Statement: CAB is a scientific advisory board member of ImmuneBridge, DeepCell, Inc., and Qihan Bio on topics unrelated to this manuscript. A.M. is a cofounder of Site Tx, Arsenal Biosciences, Spotlight Therapeutics and Survey Genomics, serves on the boards of directors at Site Tx, Spotlight Therapeutics and Survey Genomics, is a member of the scientific advisory boards of Site Tx, Arsenal Biosciences, Spotlight Therapeutics, Survey Genomics, NewLimit, Amgen, and Tenaya, owns stock in Arsenal Biosciences, Site Tx, Spotlight Therapeutics, NewLimit, Survey Genomics, Tenaya and Lightcast and has received fees from Site Tx, Arsenal Biosciences, Spotlight Therapeutics, NewLimit, 23andMe, PACT Pharma, Juno Therapeutics, Tenaya, Lightcast, Trizell, Vertex, Merck, Amgen, Genentech, GLG, ClearView Healthcare, AlphaSights, Rupert Case Management, Bernstein and ALDA. A.M. is an investor in and informal advisor to Offline Ventures and a client of EPIQ. The Marson laboratory has received research support from the Parker Institute for Cancer Immunotherapy, the Emerson Collective, Juno Therapeutics, Epinomics, Sanofi, GlaxoSmithKline, Gilead and Anthem and reagents from Genscript and Illumina.
ISSN:2692-8205
2692-8205
DOI:10.1101/2024.06.24.600449