{"doi":"10.4049/jimmunol.160.4.1618","title":"Participation of the CD94 Receptor Complex in Costimulation of Human Natural Killer Cells","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Optimal proliferation and expansion of human NK cells require mitogenic cytokines together with cell contact-dependent costimulation. Production of mAb that can modulate human NK cell proliferation yielded NKH3, which recognizes the CD94 Ag. NKH3 immunoprecipitates contain ∼70-kDa heterodimeric complexes consisting of a ∼25-kDa glycoprotein and ∼40- to 45-kDa molecules. Analysis by two-dimensional isoelectric focusing/SDS-PAGE suggests that several different 40- to 45-kDa species are present in the CD94 receptor complex in human NK cells. NKH3 reacted with essentially all resting NK cells, although CD94 is expressed at higher levels on the CD56bright (i.e., high level of CD56) CD16dim/neg (i.e., low level of or absent CD16) subpopulation than on the more abundant CD56dimCD16bright NK cell subset. Moreover, the Z199 mAb, which appears to recognize NKG2-A species that can form heterodimers with CD94, stained virtually all CD56bright NK cells, but only a subset of CD56dim NK cells. Ligation of CD94 augmented the proliferation of CD56bright NK cells in response to IL-2 or IL-15 by as much as 10-fold. Secretion of IFN-γ by CD56bright NK cells stimulated with IL-2 or IL-15 was also enhanced up to 10-fold after CD94 ligation. CD94 mAb did not consistently costimulate proliferation of or IFN-γ production by CD56dim NK cells cultured with IL-2 or IL-15. In contrast, irradiated K562 cells costimulated proliferation of both CD56bright and CD56dim NK cells. These results indicate that CD56bright and CD56dim NK cells can be costimulated through different receptors, which may allow these distinct NK cell subsets to be independently regulated in vivo.</jats:p>","journal":"The Journal of Immunology","year":1998,"id":624612,"datarank":0.6456097639806255,"base_score":4.304065093204169,"endowment":4.304065093204169,"self_citation_contribution":0.6456097639806255,"citation_network_contribution":0.0,"self_endowment_contribution":0.6456097639806255,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":73,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1387,"name":"John Daley","orcid":null,"position":1,"is_corresponding":false},{"id":34475,"name":"Jerome Ritz","orcid":"0000-0001-5526-4669","position":2,"is_corresponding":false},{"id":1614707,"name":"Michael J Robertson","orcid":null,"position":3,"is_corresponding":false},{"id":1614706,"name":"Stephan D Voss","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Participation of the CD94 Receptor Complex in Costimulation of Human Natural Killer Cells","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Optimal proliferation and expansion of human NK cells require mitogenic cytokines together with cell contact-dependent costimulation. Production of mAb that can modulate human NK cell proliferation yielded NKH3, which recognizes the CD94 Ag. NKH3 immunoprecipitates contain ∼70-kDa heterodimeric complexes consisting of a ∼25-kDa glycoprotein and ∼40- to 45-kDa molecules. Analysis by two-dimensional isoelectric focusing/SDS-PAGE suggests that several different 40- to 45-kDa species are present in the CD94 receptor complex in human NK cells. NKH3 reacted with essentially all resting NK cells, although CD94 is expressed at higher levels on the CD56bright (i.e., high level of CD56) CD16dim/neg (i.e., low level of or absent CD16) subpopulation than on the more abundant CD56dimCD16bright NK cell subset. Moreover, the Z199 mAb, which appears to recognize NKG2-A species that can form heterodimers with CD94, stained virtually all CD56bright NK cells, but only a subset of CD56dim NK cells. Ligation of CD94 augmented the proliferation of CD56bright NK cells in response to IL-2 or IL-15 by as much as 10-fold. Secretion of IFN-γ by CD56bright NK cells stimulated with IL-2 or IL-15 was also enhanced up to 10-fold after CD94 ligation. CD94 mAb did not consistently costimulate proliferation of or IFN-γ production by CD56dim NK cells cultured with IL-2 or IL-15. In contrast, irradiated K562 cells costimulated proliferation of both CD56bright and CD56dim NK cells. These results indicate that CD56bright and CD56dim NK cells can be costimulated through different receptors, which may allow these distinct NK cell subsets to be independently regulated in vivo.</jats:p>","is_dataset_classified":null,"base_score":4.304065093204169,"endowment":4.304065093204169,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"9469418","pmcid":null,"openalex_id":"https://openalex.org/W1698900496","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"T32CA59367-01A1","title":null},{"funder_name":"NCI NIH HHS","grant_id":"CA41619","title":null}],"total_grants":2,"fwci":1.422,"citation_percentile":0.80976102,"influential_citations":0,"citation_trend":[{"year":2013,"count":3},{"year":2015,"count":2},{"year":2017,"count":2},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2024,"count":2}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/160/4/1618/1079636/im049801618o.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/160/4/1618/1079636/im049801618o.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/160/4/1618/62190363/im049801618o.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.160.4.1618","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/9469418","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","CAR-T cell therapy research"],"mesh_terms":["Animals","Antibodies, Monoclonal","Cell Communication","Leukemia, Erythroblastic, Acute","Female","Humans","Killer Cells, Natural","Lymphocyte Activation","Membrane Glycoproteins","Mice, Inbred BALB C","Receptors, Mitogen","Tumor Cells, Cultured","Antigens, CD","Cytokines","CD56 Antigen","Lectins, C-Type","Mice","NK Cell Lectin-Like Receptor Subfamily D"],"keywords":["Interleukin 21","Janus kinase 3","Interleukin 12","CD49b","Biology","Cell biology","Lymphokine-activated killer cell","NK-92","CD16","Interleukin 15","Natural killer cell","K562 cells","Cell","Immunology","Cytotoxic T cell","T cell","Cytokine","Antigen","Immune system","Interleukin","In vitro","Biochemistry","CD3"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Life in Land"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T04:19:24.255389Z","pmid":null,"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":[]}