Affinage

KLRD1

Natural killer cells antigen CD94 · UniProt Q13241

Length
179 aa
Mass
20.5 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD94 (KLRD1) is an invariant C-type lectin-like type II transmembrane glycoprotein that forms obligate disulfide-bonded heterodimers with NKG2 family members to regulate NK cell and CD8+ T cell cytotoxicity through recognition of the non-classical MHC class I molecule HLA-E loaded with leader sequence-derived peptides (PMID:9486650, PMID:8943374, PMID:15940674). Pairing with NKG2A/B generates an inhibitory receptor that recruits SHP-1 via NKG2A ITIMs, leading to dephosphorylation of Vav1 and ERM proteins and disruption of actin-dependent immunological synapse assembly, thereby blocking activating receptor signaling through the Ras-ERK pathway (PMID:9565368, PMID:16951318, PMID:10358164). Pairing with NKG2C or NKG2E generates activating receptors that associate with the DAP12 ITAM-bearing adaptor to trigger cytotoxicity and cytokine production (PMID:9655483, PMID:9485212). Crystal structures of the CD94-NKG2A-HLA-E ternary complex show that CD94 makes the dominant contacts with HLA-E and mediates most peptide discrimination, while residues 167–170 in the NKG2 subunit allosterically tune receptor affinity to enforce preferential inhibitory over activating signaling (PMID:18332182, PMID:18448674).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Establishing that CD94 is an orphan C-type lectin receptor with a minimal cytoplasmic domain resolved its identity but immediately raised the question of how it signals — implying obligate partnership with other subunits.

    Evidence Molecular cloning, sequence analysis, and chromosomal mapping of CD94 from human NK cells

    PMID:7589107

    Open questions at the time
    • Signaling partner(s) not yet identified
    • Ligand unknown
    • No functional data beyond sequence inference
  2. 1996 High

    Identification of CD94's disulfide-bonded heterodimerization with NKG2A/B/C/E resolved the signaling question by showing that different NKG2 partners contribute distinct cytoplasmic domains — ITIMs for inhibition (NKG2A/B) or potential activating motifs (NKG2C/E).

    Evidence Co-immunoprecipitation and domain analysis in NK cells

    PMID:8943374

    Open questions at the time
    • Ligand still unidentified
    • Activating signaling adaptor not yet identified
    • Surface expression dependency not established
  3. 1997 High

    Demonstration that NKG2A requires CD94 for surface expression and proper glycosylation established CD94 as the obligate chaperone/partner, not merely a co-receptor.

    Evidence Co-immunoprecipitation with glycosylation analysis and anti-CD94 blocking in multiple NK clones

    PMID:9034158

    Open questions at the time
    • Ligand still unknown
    • Downstream signaling cascade undefined
  4. 1998 High

    Identification of HLA-E as the specific ligand for CD94/NKG2 receptors, with peptide-dependent recognition and functional protection of targets from NK lysis, resolved the central ligand question and linked the receptor system to MHC class I surveillance.

    Evidence HLA-E tetramer binding, NK cytotoxicity assays with HLA-E transfectants, synthetic peptide pulsing, antibody blocking across multiple independent laboratories

    PMID:9480992 PMID:9486650 PMID:9560253

    Open questions at the time
    • Structural basis of peptide discrimination unknown
    • Affinity differences between inhibitory and activating receptors not quantified
  5. 1998 High

    Discovery that activating CD94/NKG2C signals through DAP12 via transmembrane charge interactions, while inhibitory CD94/NKG2A signals through SHP-1 recruited to phosphorylated ITIMs, defined the bifurcating signaling logic of the receptor system.

    Evidence Co-IP of DAP12 with NKG2C, transmembrane mutagenesis, SHP-1 co-precipitation with phospho-NKG2A, reconstitution in RBL-2H3 cells

    PMID:9485212 PMID:9565368 PMID:9655483

    Open questions at the time
    • Downstream signaling pathway beyond SHP-1 not mapped
    • Relative ITIM contributions unknown
    • Role in T cells not established
  6. 1999 High

    Quantitative binding studies and the first CD94 crystal structure established the biophysical framework: CD94/NKG2A binds HLA-E with higher affinity than CD94/NKG2C via fast kinetics, and CD94 adopts a modified C-type lectin fold lacking a functional calcium site.

    Evidence Surface plasmon resonance with recombinant receptors; X-ray crystallography of CD94 at 2.6 Å

    PMID:10023772 PMID:10428963

    Open questions at the time
    • Heterodimer structure not yet solved
    • Structural basis for NKG2A vs NKG2C affinity difference unknown
  7. 1999 High

    Mapping of the downstream inhibitory signaling cascade showed that CD94/NKG2A blocks NK activation by interrupting CD16-triggered Syk/Shc/Grb2/ERK signaling at the level of zeta chain phosphorylation.

    Evidence Phosphorylation and kinase assays with receptor co-engagement in primary human NK cells

    PMID:10358164

    Open questions at the time
    • Actin cytoskeleton involvement not yet addressed
    • Whether signaling inhibition extends to other activating receptors untested
  8. 2002 High

    Dissection of ITIM function showed the membrane-distal Y8 ITIM is the primary SHP-1 recruitment site, while the membrane-proximal Y40 is partially redundant, establishing the hierarchy of inhibitory signaling elements within NKG2A.

    Evidence Site-directed mutagenesis of ITIM tyrosines with SHP-1 co-IP, confocal colocalization, and serotonin release inhibition in RBL transfectants

    PMID:12165520

    Open questions at the time
    • In vivo significance of individual ITIMs untested
    • Whether SHP-2 also participates not addressed
  9. 2002 High

    Discovery that hsp60-derived peptides bound to HLA-E are not recognized by CD94/NKG2A provided a mechanism for NK detection of stressed cells — loss of inhibitory recognition when the peptide repertoire shifts away from classical HLA leader sequences.

    Evidence Peptide binding, HLA-E surface measurement, and NK cytotoxicity with CD94/NKG2A+ clones

    PMID:12461076

    Open questions at the time
    • In vivo relevance during infection or tumor stress not demonstrated
    • Whether activating NKG2C recognizes stress peptides not tested
  10. 2006 High

    Elucidation of the actin-level mechanism showed that CD94/NKG2A inhibition operates by SHP-1-mediated dephosphorylation of Vav1 and ERM proteins, disrupting actin polymerization and lipid raft recruitment at the immunological synapse — placing the inhibitory block upstream of all activating receptor signaling.

    Evidence Confocal imaging of actin and raft dynamics, Vav1/ERM phosphorylation assays, pharmacological perturbation in primary NK cells

    PMID:16951318

    Open questions at the time
    • Whether this cytoskeletal mechanism applies to all inhibitory receptor families not determined
    • Quantitative threshold for inhibition unknown
  11. 2007 High

    Crystal structures of the CD94-NKG2A heterodimer and then the ternary CD94-NKG2A-HLA-E complex resolved how CD94 dominates HLA-E contact and peptide discrimination while NKG2 isoform identity tunes affinity allosterically through residues 167–170 at the heterodimer interface rather than direct ligand contact.

    Evidence X-ray crystallography at 2.5–4.4 Å resolution with structure-guided mutagenesis

    PMID:18083576 PMID:18332182 PMID:18448674

    Open questions at the time
    • No structure of CD94/NKG2C-HLA-E complex for direct activating receptor comparison
    • Membrane-proximal signaling complex architecture unknown
  12. 2011 High

    Genetic ablation of CD94 in mice demonstrated in vivo essentiality: CD94-knockout mice succumbed to mousepox, with the activating CD94-NKG2E receptor recognizing Qa-1b on infected cells as the protective mechanism, establishing CD94 as indispensable for antiviral innate immunity.

    Evidence CD94-knockout mouse challenged with ectromelia virus, NK depletion, Qa-1b blocking

    PMID:21439856

    Open questions at the time
    • Whether CD94/NKG2E recognizes virus-derived peptides in Qa-1b not determined
    • Human relevance of NKG2E-specific antiviral role unclear
  13. 2021 High

    NKG2A knockout revealed that the CD94/NKG2A inhibitory receptor educates uterine NK cells required for placental vascular remodeling; its loss causes pre-eclampsia-like features, establishing a non-redundant role for inhibitory CD94/NKG2A signaling in reproductive immunology.

    Evidence NKG2A-knockout mouse with placental/fetal phenotyping plus GWAS validation in human pre-eclampsia cohorts

    PMID:33887202

    Open questions at the time
    • Mechanism linking NK education to vascular remodeling not fully defined
    • Whether CD94/NKG2C compensates partially in this context untested
  14. 2023 High

    Systematic analysis of all 16 common HLA class I signal peptide variants revealed that only 6 efficiently engage CD94/NKG2 receptors, and the HLA-B/-21M dimorphism paradoxically increases HLA-E expression while reducing receptor engagement, demonstrating that peptide quality — not just HLA-E quantity — governs NK cell education.

    Evidence Quantitative peptide binding, HLA-E expression, and CD94/NKG2A/NKG2C functional assays with 16 signal peptide variants

    PMID:37264229

    Open questions at the time
    • How peptide competition shapes the overall HLA-E peptidome in vivo is not resolved
    • Impact on NK education threshold quantitatively undefined
  15. 2024 High

    Discovery that LAG-3 sustains a CD94/NKG2+ subset of exhausted CD8 T cells that kill via Qa-1b recognition expanded the receptor's role beyond NK cells into T cell exhaustion biology and checkpoint immunotherapy.

    Evidence Genetic knockout of LAG-3/PD-1 in chronic infection model with transcriptomics and Qa-1b blocking

    PMID:39121847

    Open questions at the time
    • Whether therapeutic LAG-3 blockade disrupts CD94/NKG2 function in patients untested
    • Identity of Qa-1b-bound peptides driving this recognition unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for activating CD94/NKG2C-HLA-E recognition, the in vivo peptidome presented by HLA-E to CD94/NKG2 receptors during infection and cancer, and how CD94/NKG2 receptor balance integrates with KIR and other checkpoint signals to set the NK cell activation threshold.
  • No crystal structure of activating CD94/NKG2C-HLA-E complex
  • In vivo HLA-E peptidome during disease states not characterized
  • Quantitative integration with KIR and other checkpoint receptors not modeled

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5
Partners
HLA-EKLRC1KLRC2KLRC3PTPN6TYROBP
Complex memberships
CD94/NKG2ACD94/NKG2CCD94/NKG2E

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 CD94 is a type II membrane glycoprotein encoded by a unique gene of the C-type lectin superfamily, located on human chromosome 12, and has an essentially absent cytoplasmic domain, implying association with other receptors is necessary for its function. Molecular cloning, sequence analysis, chromosomal mapping European journal of immunology High 7589107
1996 CD94 forms disulfide-bonded heterodimers with NKG2A/B, NKG2C, and NKG2E glycoproteins; NKG2A/B contains two ITIM sequences in its cytoplasmic domain mediating inhibitory function, whereas other NKG2 partners lack ITIMs and may transmit positive signals. Biochemical co-immunoprecipitation, structural domain analysis Journal of immunology High 8943374
1997 NKG2A (43 kDa) is covalently associated with CD94 on the NK cell surface; surface expression of NKG2A requires association with CD94 (glycosylation patterns of mature NKG2A only found when associated with CD94); the CD94/NKG2A complex delivers an inhibitory signal via its two ITIMs. Co-immunoprecipitation, glycosylation analysis, functional blocking with anti-CD94 mAb The Journal of experimental medicine High 9034158
1998 HLA-E is the specific ligand for CD94/NKG2A, CD94/NKG2B, and CD94/NKG2C receptors; HLA-E tetramers bound to NK cells and transfectants expressing these receptors but not to KIR family receptors; surface HLA-E expression protected target cells from lysis by CD94/NKG2A+ NK clones. HLA-E tetramer binding assay, NK cell cytotoxicity assay, transfectant cell lines Nature High 9486650
1998 CD94/NKG2A specifically recognizes HLA-E; antibodies against HLA-E, CD94, or CD94/NKG2A restored NK-mediated lysis of HLA-E+ targets; surface stabilization of HLA-E by appropriate leader-sequence peptides was sufficient to confer protection via CD94/NKG2A. NK cytotoxicity assay with antibody blocking, peptide-pulsed target cells, transfectants Proceedings of the National Academy of Sciences High 9560253
1998 NK cells recognize HLA-E molecules via the CD94/NKG2A heterodimer, resulting in inhibition of cytolysis; only HLA class I signal peptides containing Met at position 2 (of the HLA-E binding peptide) conferred resistance to NK-mediated lysis, whereas Thr at position 2 did not, establishing peptide-dependent recognition. NK cytotoxicity assay, synthetic peptide pulsing of target cells, anti-CD94 blocking The Journal of experimental medicine High 9480992
1998 The activating CD94/NKG2C receptor associates with DAP12 (an ITAM-containing signaling adaptor); efficient surface expression of CD94/NKG2C requires DAP12; charged residues in the transmembrane domains of DAP12 and NKG2C are required for this interaction. Co-immunoprecipitation, transfection with transmembrane domain mutants, surface expression analysis Immunity High 9655483
1998 The activating CD94-associated 39-kDa protein (Kp39) is the product of the NKG2-C gene; NKG2-C covalently associates with CD94 to form an activating receptor complex in a subset of NK cells lacking NKG2-A expression, and its engagement triggers cytolytic activity. Immunoprecipitation, peptide mapping, RT-PCR on NK clones, redirected killing assay, COS7 co-transfection European journal of immunology High 9485212
1998 Engagement of CD94/NKG2A by HLA-E induces tyrosine phosphorylation of the NKG2A subunit and recruitment of SHP-1 phosphatase; these biochemical events are the mechanistic basis for inhibitory signaling; reconstituted in heterologous RBL-2H3 transfectants. Western blot/phosphorylation assay, co-immunoprecipitation of SHP-1 with NKG2A, RBL transfectant reconstitution, serotonin release inhibition assay European journal of immunology High 9565368
1998 CD94/NKG2A is involved in NK cell recognition of HLA-G1; CD94-specific mAbs reconstituted cytolytic activity against HLA-G1 transfectants comparably to anti-HLA class I mAbs, establishing CD94/NKG2A as the predominant inhibitory receptor for HLA-G. NK cytotoxicity assay, antibody blocking with anti-CD94 and anti-HLA mAbs, transfectant target cells Journal of immunology High 9190923 9233599
1998 The primary structure of HLA-E-bound peptides influences CD94/NKG2-mediated recognition beyond their ability to stabilize surface HLA-E; the HLA-G-derived nonamer triggered cytotoxicity very efficiently through the activating CD94/NKG2C receptor, suggesting higher affinity interaction. NK clone cytotoxicity assays with panel of synthetic peptide-loaded HLA-E transfectants European journal of immunology High 9754572
1999 Soluble CD94/NKG2A has higher binding affinity for HLA-E than CD94/NKG2C; both receptors show fast association and dissociation kinetics; recognition of HLA-E by both receptors is peptide-dependent; binding affinity of the peptide-HLA-E complex directly correlates with the NK cell response. Surface plasmon resonance/binding kinetics with soluble recombinant receptors and HLA-E tetramers, functional NK assays The EMBO journal High 10428963
1999 CD94/NKG2A specifically recognizes HLA-E and not classical HLA class I molecules; this interaction is strictly dependent on peptide binding to HLA-E (peptide stabilizes surface expression AND must form a recognized complex); all class I leader sequence peptides tested were recognized but amino acid variations affected recognition. Soluble CD94/NKG2A direct binding assay, NK cell functional assays, HLA-E transfectants Journal of immunology High 9886400
1999 Crystal structure of the extracellular domain of CD94 reveals a unique C-type lectin fold in which the second alpha helix is replaced by a loop and the calcium-binding site is nonfunctional; the CD94 dimer interface reveals a putative HLA-E binding region and suggests how NKG2 interacts with CD94. X-ray crystallography at 2.6 Å resolution Immunity High 10023772
1999 CD94/NKG2A inhibitory signaling blocks CD16-triggered Syk kinase activation and ERK activation by impairing tyrosine phosphorylation of the CD16 zeta subunit, Shc adaptor protein phosphorylation, and Shc/Grb-2 complex formation, thereby blocking the Ras-ERK pathway required for cytotoxicity. Western blot phosphorylation assays, kinase activity assays, receptor co-engagement experiments in human NK cells Journal of immunology High 10358164
2002 A peptide derived from the signal sequence of heat shock protein 60 (hsp60) binds HLA-E intracellularly, upregulates HLA-E/hsp60 surface levels on stressed cells, and the resulting complex is NOT recognized by CD94/NKG2A inhibitory receptors, providing a mechanism for NK cells to detect stressed cells. Peptide binding assay, surface HLA-E flow cytometry, NK cytotoxicity assay with CD94/NKG2A+ clones The Journal of experimental medicine High 12461076
2002 Both NKG2A ITIMs are required for maximal CD94/NKG2A inhibitory signaling; the membrane-distal ITIM (Y8) is of primary importance; Y8F mutation alone largely abolished SHP-1 colocalization and inhibition of FcεRI-mediated serotonin release, while Y40F retained ~70% inhibitory function. Site-directed mutagenesis of ITIM tyrosines, transfection into RBL-2H3, phosphorylation assays, SHP-1 co-immunoprecipitation, confocal microscopy, serotonin release inhibition assay Journal of immunology High 12165520
2002 CD94/NKG2A receptors continuously recycle between cell surface and intracellular endosomal compartments in an energy- and cytoskeleton-dependent process that is independent of ligand binding or functional ITIM signaling; this trafficking is distinct from that of the activating CD94/NKG2C receptor. Flow cytometry, confocal microscopy, biochemical fractionation, ITIM mutant transfection in RBL-2H3 cells Journal of immunology High 12444112
2003 Full-length Hsp70 protein and the Hsp70 C-terminal domain bind specifically to CD94 on NK cells; CD94-specific antibody completely abrogated Hsp70 binding; binding is concentration-dependent and specific (competition with unlabeled Hsp70 but not unrelated protein); the 14-mer Hsp70 peptide TKD also binds CD94. Immunofluorescence binding studies, antibody blocking, competition assay with unlabeled proteins, dose-response binding Biological chemistry Medium 12675520
2006 CD94/NKG2A inhibitory signaling prevents NK cell activation by disrupting actin network organization at the immunological synapse (iNKIS) and excluding lipid rafts from the contact site; mechanistically, SHP-1 is recruited and activated, leading to dephosphorylation of Vav1 (a guanine nucleotide exchange factor) and ezrin-radixin-moesin proteins, blocking actin-dependent recruitment of activation receptor complexes. Confocal microscopy of actin and lipid raft dynamics, phosphorylation assays for Vav1 and ERM proteins, pharmacological inhibition of actin polymerization and cholesterol depletion Journal of immunology High 16951318
2007 Crystal structure of CD94-NKG2A heterodimer at 2.5 Å reveals asymmetric dimerization interface despite structural homology between subunits, providing structural basis for preferred heterodimeric (vs. homodimeric) assembly; the invariant CD94 chain plays a dominant role in interacting with HLA-E compared to the variable NKG2 chain. X-ray crystallography at 2.5 Å, structure-based mutagenesis of HLA-E and CD94-NKG2A Immunity High 18083576
2008 Crystal structure of CD94-NKG2A in complex with HLA-E bound to HLA-G leader sequence peptide shows CD94 subunit dominates the interaction with HLA-E while NKG2A is more peripheral; CD94 dominates peptide-mediated contacts; 'lock and key' binding mode with few conformational changes upon ligation. X-ray crystallography of ternary complex, mutagenesis at CD94-NKG2A-HLA-E interface The Journal of experimental medicine High 18332182
2008 Crystal structure of NKG2A/CD94/HLA-E at 4.4 Å confirms CD94 contacts the C-terminal region of the peptide (most variable among class I leader sequences); residues 167-170 of NKG2A/C account for the ~6-fold higher affinity of inhibitory NKG2A/CD94 vs. activating NKG2C/CD94 through effects at the CD94-NKG2 heterodimer interface rather than direct HLA-E contact. X-ray crystallography, binding affinity measurement, evolutionary analysis Proceedings of the National Academy of Sciences High 18448674
2008 Subtle changes in peptide conformation within the HLA-E binding groove (without changes in HLA-E heavy chain conformation) explain differential recognition by CD94-NKG2 receptors; HLA-Cw*07 peptide (poorly recognized) and HLA-G*01 peptide (high-affinity ligand) differ in peptide conformation within the groove. X-ray crystallography of HLA-E with two different leader peptides at 2.5 Å resolution Journal of molecular biology High 18339401
2011 CD94 is essential for resistance to mousepox; ectromelia virus-infected cells expressing Qa-1(b) are specifically recognized by the activating receptor CD94-NKG2E, establishing the molecular mechanism of NK-mediated antiviral defense in this model. CD94-knockout mouse, viral challenge model, NK cell depletion, Qa-1(b) blocking Immunity High 21439856
2021 The CD94/NKG2A inhibitory receptor educates uterine NK cells required for optimal pregnancy outcomes; NKG2A genetic ablation caused suboptimal maternal vascular responses, perturbed placental gene expression, reduced fetal weight, and features resembling pre-eclampsia; the maternal HLA-B→HLA-E→NKG2A pathway drives NK education for healthy pregnancy. NKG2A knockout mouse, placental and fetal phenotyping, GWAS of pre-eclampsia cases, genetic epistasis Immunity High 33887202
2000 CD69-triggered ERK activation and degranulation are negatively regulated by co-engagement of CD94/NKG2A; in RBL transfectants expressing both receptors, CD94/NKG2A suppressed CD69-mediated ERK activation and cell degranulation; in human NK cells, CD94/NKG2A inhibited CD69-induced cytotoxicity. RBL transfectant co-expression system, ERK phosphorylation assay, degranulation assay, NK cytotoxicity assay European journal of immunology High 10671222
2004 CD94/NKG2A and CD94/NKG2C bind mostly shared but partly distinct sets of HLA-E residues at the top of the α1/α2 domain; two HLA-E mutations (D69A and H155A) selectively abrogated binding to CD94/NKG2A but not CD94/NKG2C, demonstrating partial epitope discrimination. Alanine scanning mutagenesis of HLA-E, binding assay with soluble CD94/NKG2A and CD94/NKG2C European journal of immunology High 14971033
2005 CD94/NKG2C couples to DAP12 in T cells as well as NK cells; specific engagement of CD94/NKG2C on CD8+ T cell clones triggered cytotoxicity, cytokine production, IL-2Rα upregulation and proliferative responses via DAP12 co-precipitation with anti-CD94 antibody. Co-immunoprecipitation of DAP12 with CD94/NKG2C in T cell clones, functional assays (cytotoxicity, cytokine production, proliferation) European journal of immunology High 15940674
2005 CD94/NKG2A on NK cells inhibits NK killing of immature dendritic cells (iDC) in proportion to receptor surface density; iDC downregulate HLA-E expression, reducing inhibitory signaling and enabling lysis by CD94/NKG2A+KIR− NK cells; mature DC with higher HLA-E are protected. NK-DC co-culture cytotoxicity assay, flow cytometric phenotyping, HLA-E expression measurement European journal of immunology Medium 12778484
2023 Among 16 common HLA class I signal peptide variants, only 6 ('functional SPs') efficiently generate epitopes enabling CD94/NKG2 engagement; HLA-B/-21M induces high HLA-E expression but confers the lowest receptor recognition and competes with other SPs, reducing overall CD94/NKG2A recognition of target cells. Systematic peptide binding assay, HLA-E surface expression measurement, CD94/NKG2A/NKG2C functional recognition assays, population genetics analysis Nature immunology High 37264229
2024 LAG-3 sustains TOX expression in exhausted CD8 T cells and regulates a LAG-3-dependent circuit that generates a CD94/NKG2+ subset of exhausted T cells with enhanced cytotoxicity mediated by recognition of the stress ligand Qa-1b; loss of LAG-3 disrupts this CD94/NKG2-Qa-1b axis. Genetic KO of PD-1 and/or LAG-3 in chronic infection model, transcriptomics, functional cytotoxicity assay, Qa-1b blocking Cell High 39121847

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1811 9486650
1998 HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proceedings of the National Academy of Sciences of the United States of America 837 9560253
1998 Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis. The Journal of experimental medicine 567 9480992
1998 Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 429 9655483
2005 Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood 355 16384928
1998 Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1(b). The Journal of experimental medicine 355 9815261
1996 Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. Journal of immunology (Baltimore, Md. : 1950) 352 8943374
1998 HLA-E-bound peptides influence recognition by inhibitory and triggering CD94/NKG2 receptors: preferential response to an HLA-G-derived nonamer. European journal of immunology 311 9754572
1999 Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2-A and the activating receptor CD94/NKG2-C to HLA-E. The EMBO journal 298 10428963
2000 HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. European journal of immunology 290 10898498
2023 Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance. Cancer cell 258 36706761
1994 Human natural killer cell receptors for HLA-class I molecules. Evidence that the Kp43 (CD94) molecule functions as receptor for HLA-B alleles. The Journal of experimental medicine 223 8046333
1997 NKG2A complexed with CD94 defines a novel inhibitory natural killer cell receptor. The Journal of experimental medicine 212 9034158
2002 A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition. The Journal of experimental medicine 203 12461076
1995 Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. European journal of immunology 201 7589107
2009 CD94 surface density identifies a functional intermediary between the CD56bright and CD56dim human NK-cell subsets. Blood 196 19897577
1998 HLA class I-specific inhibitory receptors in human T lymphocytes: interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells. Proceedings of the National Academy of Sciences of the United States of America 194 9448304
2003 The natural killer cell-mediated killing of autologous dendritic cells is confined to a cell subset expressing CD94/NKG2A, but lacking inhibitory killer Ig-like receptors. European journal of immunology 193 12778484
2008 CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I leader sequence. The Journal of experimental medicine 190 18332182
2000 Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease. Gastroenterology 185 10784586
2008 Structural basis for NKG2A/CD94 recognition of HLA-E. Proceedings of the National Academy of Sciences of the United States of America 176 18448674
2002 IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. The Journal of clinical investigation 175 12438449
1999 Recognition of the class Ib molecule Qa-1(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on mouse natural killer cells. The Journal of experimental medicine 166 10601355
1999 Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes. European journal of immunology 163 9933082
2002 CD94-NKG2A receptors regulate antiviral CD8(+) T cell responses. Nature immunology 159 11812997
2003 Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biological chemistry 151 12675520
2012 Cytotoxicity of CD56(bright) NK cells towards autologous activated CD4+ T cells is mediated through NKG2D, LFA-1 and TRAIL and dampened via CD94/NKG2A. PloS one 148 22384114
1997 Interleukin-15-induced maturation of human natural killer cells from early thymic precursors: selective expression of CD94/NKG2-A as the only HLA class I-specific inhibitory receptor. European journal of immunology 138 9209487
1997 CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 129 9550399
1999 Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells. Journal of immunology (Baltimore, Md. : 1950) 126 9886400
1997 Structure and function of the CD94 C-type lectin receptor complex involved in recognition of HLA class I molecules. Immunological reviews 120 9059892
2006 The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunologic research 118 17172651
2016 Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. Oncoimmunology 116 27853650
2005 Up-regulation of inhibitory natural killer receptors CD94/NKG2A with suppressed intracellular perforin expression of tumor-infiltrating CD8+ T lymphocytes in human cervical carcinoma. Cancer research 115 15805295
1999 Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. Immunity 111 10023772
1999 Response of murine and normal human skin to injection of allogeneic blood-derived psoriatic immunocytes: detection of T cells expressing receptors typically present on natural killer cells, including CD94, CD158, and CD161. Archives of dermatology 110 10328195
1997 The CD94/NKG2-A inhibitory receptor complex is involved in natural killer cell-mediated recognition of cells expressing HLA-G1. Journal of immunology (Baltimore, Md. : 1950) 109 9190923
2002 TCR specificity dictates CD94/NKG2A expression by human CTL. Immunity 107 12387742
1998 Specific engagement of the CD94/NKG2-A killer inhibitory receptor by the HLA-E class Ib molecule induces SHP-1 phosphatase recruitment to tyrosine-phosphorylated NKG2-A: evidence for receptor function in heterologous transfectants. European journal of immunology 101 9565368
1998 Murine Nkg2d and Cd94 are clustered within the natural killer complex and are expressed independently in natural killer cells. Proceedings of the National Academy of Sciences of the United States of America 100 9600963
2004 The role of CD94/NKG2 in innate and adaptive immunity. Immunologic research 98 15258309
1997 CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells. Journal of immunology (Baltimore, Md. : 1950) 95 9233599
2014 The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Seminars in immunology 93 24666761
2011 CD94 is essential for NK cell-mediated resistance to a lethal viral disease. Immunity 93 21439856
1998 The activating form of CD94 receptor complex: CD94 covalently associates with the Kp39 protein that represents the product of the NKG2-C gene. European journal of immunology 93 9485212
1997 Cloning of a mouse homolog of CD94 extends the family of C-type lectins on murine natural killer cells. European journal of immunology 93 9464811
1995 Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen. Journal of immunology (Baltimore, Md. : 1950) 92 7751628
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2004 The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E residues. European journal of immunology 79 14971033
2019 Enriched HLA-E and CD94/NKG2A Interaction Limits Antitumor CD8+ Tumor-Infiltrating T Lymphocyte Responses. Cancer immunology research 77 31213473
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2021 The CD94/NKG2A inhibitory receptor educates uterine NK cells to optimize pregnancy outcomes in humans and mice. Immunity 73 33887202
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2007 Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion. Immunology 67 17521371
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2006 Qa-1b and CD94-NKG2a interaction regulate cytolytic activity of herpes simplex virus-specific memory CD8+ T cells in the latently infected trigeminal ganglia. Journal of immunology (Baltimore, Md. : 1950) 60 16424200
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1999 Cutting edge: expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly-49- cells: a possible mechanism of tolerance during NK cell development. Journal of immunology (Baltimore, Md. : 1950) 58 10358137
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1999 CD94/NKG2-A inhibitory complex blocks CD16-triggered Syk and extracellular regulated kinase activation, leading to cytotoxic function of human NK cells. Journal of immunology (Baltimore, Md. : 1950) 37 10358164
2014 Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts. Immunology 36 24673109
2006 Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and induces apoptotic death of naive natural killer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 36 16609008
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