Antigen-specific memory NK cell responses against HIV and influenza utilize the NKG2/HLA-E axis

For over a decade, multiple studies have disputed the notion of natural killer (NK) cells as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including two critical global health priorities – human immunodeficiency virus (HIV) and influenza. However, the mechanisms underlying antigen specificity remain unknown. Herein, 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, and confirm these findings by three rigorous assays. We validated the permanent acquisition of antigen-specificity by individual memory NK cells by single-cell cloning. We identified biomarkers of antigen-specific NK cell memory through complex immunophenotyping by 30-parameter flow cytometry showing elevated expression of KLR..., , , # Antigen-specific memory NK cell responses against HIV and influenza utilize the NKG2/HLA-E axis

For over a decade, multiple studies have disputed the notion of natural killer (NK) cells as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including human immunodeficiency virus (HIV) and influenza. However, the mechanisms underlying antigen specificity remain unknown. Altogether, these datasets were used to 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, and confirm these findings by three rigorous assays. We validated the permanent acquisition of antigen-specificity by individual memory NK cells by single-cell cloning. We identified biomarkers of antigen-specific NK cell memory through com...