{"doi":"10.1126/sciimmunol.adi3974","title":"Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis","abstract":"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.","journal":"Science Immunology","year":2023,"id":318255,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":67,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945382,"name":"Olivier Lucar","orcid":"0000-0002-8469-4454","position":1,"is_corresponding":false},{"id":412274,"name":"Esther Lee","orcid":"0000-0003-1149-6331","position":2,"is_corresponding":false},{"id":1025332,"name":"Taylor Yoder","orcid":"0009-0002-6077-5206","position":3,"is_corresponding":false},{"id":435422,"name":"Kyle Kroll","orcid":"0000-0002-9237-9497","position":4,"is_corresponding":false},{"id":494501,"name":"Sho K. Sugawara","orcid":"0000-0002-5187-423X","position":5,"is_corresponding":false},{"id":304850,"name":"Scott Smith","orcid":"0000-0003-3581-9908","position":6,"is_corresponding":false},{"id":81675,"name":"Rhianna Jones","orcid":null,"position":7,"is_corresponding":false},{"id":1025333,"name":"George Tweet","orcid":"0009-0004-7811-1744","position":8,"is_corresponding":false},{"id":1025334,"name":"Alexandra Werner","orcid":"0000-0002-9350-443X","position":9,"is_corresponding":false},{"id":496268,"name":"Phillip J. Tomezsko","orcid":"0000-0003-1864-4130","position":10,"is_corresponding":false},{"id":233143,"name":"Haley L. Dugan","orcid":"0000-0003-2238-0094","position":11,"is_corresponding":false},{"id":1025335,"name":"Joshua Ghofrani","orcid":"0000-0002-5956-9096","position":12,"is_corresponding":false},{"id":410081,"name":"Philippe Rascle","orcid":"0000-0001-8860-3938","position":13,"is_corresponding":false},{"id":496307,"name":"Marcus Altfeld","orcid":"0000-0001-5972-2997","position":14,"is_corresponding":false},{"id":410086,"name":"Michaela Müller‐Trutwin","orcid":"0000-0002-3854-2396","position":15,"is_corresponding":false},{"id":240555,"name":"Paul Goepfert","orcid":"0000-0001-8441-5737","position":16,"is_corresponding":false},{"id":107632,"name":"R. Keith Reeves","orcid":"0000-0003-3157-2557","position":17,"is_corresponding":false},{"id":778384,"name":"Stéphanie Jost","orcid":"0000-0003-2100-3262","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T01:07:01.300821Z","pmid":"38064568","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}