Antigen-specific memory NK cell responses against HIV and influenza utilize the NKG2/HLA-E axis
Author ORCID
Stephanie Jost 0000-0003-2100-3262
Taylor Yoder 0009-0002-6077-5206
Kyle Kroll 0000-0002-9237-9497
Sho Sugawara 0000-0002-5187-423X
George Tweet 0009-0004-7811-1744
Haley Dugan 0000-0003-2238-0094
Joshua Ghofrani 0000-0002-5956-9096
Michaela Müller-Trutwin 0000-0002-3854-2396
Paul Goepfert 0000-0001-8441-5737
R. Keith Reeves 0000-0003-3157-2557
Publication Date
5-24-2024
Abstract
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 KLRG1, a4b7, and NKG2C. Finally, we show 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 behind antigen-specific memory NK cell responses, and suggest they could be targeted for future vaccines, cure strategies, or other therapeutic interventions.
Keywords
natural killer cell, HIV, Influenza
Repository
Dryad
Distribution License
CC0 1.0 Universal - No copyright; this work is in the public domain
Access Instructions and Link
This data is public domain under the CC-0.0 License
Recommended Citation
Jost, Stephanie; Lucar, Olivier; Lee, Esther; Yoder, Taylor; Kroll, Kyle; Sugawara, Sho; Smith, Scott; Jones, Rhianna; Tweet, George; Werner, Alexandra; Tomezsko, Phillip; Dugan, Haley; Ghofrani, Joshua; Rascle, Philippe; Altfeld, Marcus; Müller-Trutwin, Michaela; Goepfert, Paul; and Reeves, R Keith, "Antigen-specific memory NK cell responses against HIV and influenza utilize the NKG2/HLA-E axis" (2024). UAB Research Data Catalog. 119.
https://digitalcommons.library.uab.edu/datasets/119
