tetano
Editor, Senior Moderator
Sci Immunol
. 2023 Dec 8;8(90):eadi3974.
doi: 10.1126/sciimmunol.adi3974. Epub 2023 Dec 8. Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis
Stephanie Jost[SUP] 1 2 [/SUP], Olivier Lucar[SUP] 1 [/SUP], Esther Lee[SUP] 1 2 [/SUP], Taylor Yoder[SUP] 1 [/SUP], Kyle Kroll[SUP] 1 2 [/SUP], Sho Sugawara[SUP] 1 2 [/SUP], Scott Smith[SUP] 1 [/SUP], Rhianna Jones[SUP] 1 2 [/SUP], George Tweet[SUP] 1 [/SUP], Alexandra Werner[SUP] 1 [/SUP], Phillip J Tomezsko[SUP] 3 [/SUP], Haley L Dugan[SUP] 3 [/SUP], Joshua Ghofrani[SUP] 1 [/SUP], Philippe Rascle[SUP] 1 2 [/SUP], Marcus Altfeld[SUP] 4 [/SUP], Michaela Müller-Trutwin[SUP] 5 [/SUP], Paul Goepfert[SUP] 6 [/SUP], R Keith Reeves[SUP] 1 2 3 [/SUP]
Affiliations
Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E. We validated the permanent acquisition of antigen specificity by individual memory NK cells by single-cell cloning. We identified elevated expression of KLRG1, α4β7, and NKG2C as biomarkers of antigen-specific NK cell memory through complex immunophenotyping. Last, we uncovered individual HLA-E-restricted peptides that may constitute the dominant NK cell response in HIV-1- and influenza-infected persons in vivo. Our findings clarify the mechanisms contributing to antigen-specific memory NK cell responses and suggest that they could be potentially targeted therapeutically for vaccines or other therapeutic interventions.
. 2023 Dec 8;8(90):eadi3974.
doi: 10.1126/sciimmunol.adi3974. Epub 2023 Dec 8. Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis
Stephanie Jost[SUP] 1 2 [/SUP], Olivier Lucar[SUP] 1 [/SUP], Esther Lee[SUP] 1 2 [/SUP], Taylor Yoder[SUP] 1 [/SUP], Kyle Kroll[SUP] 1 2 [/SUP], Sho Sugawara[SUP] 1 2 [/SUP], Scott Smith[SUP] 1 [/SUP], Rhianna Jones[SUP] 1 2 [/SUP], George Tweet[SUP] 1 [/SUP], Alexandra Werner[SUP] 1 [/SUP], Phillip J Tomezsko[SUP] 3 [/SUP], Haley L Dugan[SUP] 3 [/SUP], Joshua Ghofrani[SUP] 1 [/SUP], Philippe Rascle[SUP] 1 2 [/SUP], Marcus Altfeld[SUP] 4 [/SUP], Michaela Müller-Trutwin[SUP] 5 [/SUP], Paul Goepfert[SUP] 6 [/SUP], R Keith Reeves[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 38064568
- DOI: 10.1126/sciimmunol.adi3974
Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E. We validated the permanent acquisition of antigen specificity by individual memory NK cells by single-cell cloning. We identified elevated expression of KLRG1, α4β7, and NKG2C as biomarkers of antigen-specific NK cell memory through complex immunophenotyping. Last, we uncovered individual HLA-E-restricted peptides that may constitute the dominant NK cell response in HIV-1- and influenza-infected persons in vivo. Our findings clarify the mechanisms contributing to antigen-specific memory NK cell responses and suggest that they could be potentially targeted therapeutically for vaccines or other therapeutic interventions.