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

• DOI: 10.1126/sciimmunol.adi3974
• Publication Date: 2023-12-08T18:58:07Z
• Authors: Stephanie Jost; Olivier Lucar; Esther Lee; Taylor Yoder; Kyle Kroll; Sho Sugawara; Scott Smith; Rhianna Jones; George Tweet; Alexandra Werner; Phillip J. Tomezsko; Haley L. Dugan; Joshua Ghofrani; Philippe Rascle; Marcus Altfeld; Michaela Müller-T...; Paul Goepfert; R. Keith Reeves
• Keywords: Killer Cells, Natural; Histocompatibility Antigens Class I; Influenza, Human; Humans; HIV Infections; NK Cell Lectin-Like Receptor Subfamily C; HLA-E Antigens

Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, mechanisms underlying antigen specificity remain unknown. Here, we demonstrate human NK cell develops upon exposure to both HIV influenza, unified a conserved epitope-specific targetable mechanism largely dependent on activating CD94/NKG2C receptor its ligand HLA-E. We validated permanent acquisition individual single-cell cloning. identified elevated expression KLRG1, α4β7, NKG2C biomarkers through complex immunophenotyping. Last, uncovered HLA-E-restricted peptides may constitute dominant response in HIV-1- influenza-infected persons vivo. Our findings clarify contributing responses suggest could be potentially targeted therapeutically for vaccines or other therapeutic interventions.