Affinage

KLRC1

NKG2-A/NKG2-B type II integral membrane protein · UniProt P26715

Length
233 aa
Mass
26.3 kDa
Annotated
2026-06-10
88 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLRC1 encodes NKG2-A, the inhibitory subunit of the CD94/NKG2-A heterodimeric receptor that governs the activation threshold of NK cells and T cell subsets by sensing HLA class I status through the non-classical ligand HLA-E (PMID:2007850, PMID:9480992). NKG2-A is a type II C-type lectin domain protein that assembles into disulfide-bonded heterodimers with CD94 and carries two cytoplasmic ITIMs that constitute the inhibitory signaling module (PMID:2007850, PMID:8943374). Upon engagement of HLA-E — whose surface display depends on loading of peptides derived from HLA class I signal sequences — NKG2-A becomes tyrosine-phosphorylated and selectively recruits the SHP-1 phosphatase (PMID:9480992, PMID:9565368, PMID:9103421). SHP-1 recruitment dampens activating signaling, blocking Syk activation, CD16 ζ-chain phosphorylation, Shc/Grb-2 complex formation upstream of p21ras, and downstream ERK activation, thereby suppressing degranulation, cytotoxicity, and cytokine production triggered through CD16 and CD69 (PMID:10358164, PMID:10671222). Recognition is peptide-tuned: HLA-E-bound peptide identity dictates binding affinity and the functional outcome, with soluble CD94/NKG2-A binding HLA-E with higher affinity than the activating CD94/NKG2-C counterpart, and only a subset of common signal-peptide variants efficiently generating engaging epitopes (PMID:10428963, PMID:9754572, PMID:37264229). Crystallography established that CD94/NKG2-A forms an asymmetric heterodimer in which CD94 is the dominant HLA-E contact subunit, and that subtle peptide conformational changes within the HLA-E groove — not the heavy chain — determine differential receptor recognition (PMID:18083576, PMID:18339401). This axis operates across biological contexts, including inhibition of decidual NK cells via HLA-E on trophoblast, regulation of iNKT and exhausted CD8 T cell responses through the murine HLA-E homolog Qa-1, and microglia–neuron signaling controlling cortical plasticity (PMID:10898498, PMID:15746081, PMID:39121847, PMID:35648829). Genetic disruption of KLRC1 in human NK cells relieves HLA-E-mediated inhibition and enhances anti-tumor cytotoxicity, establishing NKG2-A as an actionable immunotherapy checkpoint (PMID:37675109, PMID:39815622).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Established the molecular identity of KLRC1 as an NK-restricted type II membrane C-type lectin protein, defining the gene and its NKG2-A/NKG2-B splice products as candidate NK receptors.

    Evidence cDNA cloning, sequence analysis, and Northern blotting of NK-derived transcripts

    PMID:2007850

    Open questions at the time
    • No ligand identified
    • No receptor partner or signaling function defined
  2. 1996 High

    Defined the structural and signaling basis for inhibitory function by showing NKG2-A heterodimerizes with CD94 and carries two cytoplasmic ITIMs.

    Evidence Immunoprecipitation and sequence analysis on NK cells

    PMID:8943374

    Open questions at the time
    • ITIM-recruited effector phosphatase not yet identified
    • Physiological ligand not defined
  3. 1997 High

    Showed that the CD94/NKG2-A complex transduces inhibitory signals through selective recruitment of SHP-1, linking the ITIMs to a defined phosphatase effector.

    Evidence Chimeric receptor transfection into rat NK line, cytotoxicity and calcium assays, SHP-1 co-IP

    PMID:9045931 PMID:9103421

    Open questions at the time
    • Downstream activating substrates dephosphorylated not yet mapped
    • Native ligand still uncertain
  4. 1998 High

    Identified HLA-E as the ligand and established that signal-peptide loading and peptide identity (Met at position 2) control surface HLA-E and inhibitory recognition.

    Evidence Peptide loading of HLA-E on 721.221 cells, NK cytotoxicity, mAb blocking, plus phosphorylation/SHP-1 recruitment in RBL transfectants

    PMID:9480992 PMID:9565368 PMID:9754572

    Open questions at the time
    • Quantitative binding affinities not yet measured
    • Atomic basis of peptide discrimination unknown
  5. 1999 High

    Quantified the receptor-ligand interaction and dissected the signaling block, showing NKG2-A binds HLA-E with higher affinity than NKG2-C and inhibits at a PTK-dependent step upstream of ERK.

    Evidence Surface plasmon resonance with soluble proteins; biochemical co-engagement of CD94/NKG2-A and CD16 in primary NK cells

    PMID:10358164 PMID:10428963

    Open questions at the time
    • Structural detail of the heterodimer not yet resolved
    • Generality across activating receptors only partly tested
  6. 1999 High

    Provided atomic-level information on CD94, revealing a modified C-type lectin fold with non-functional Ca2+ and carbohydrate sites and a putative HLA-E binding region.

    Evidence X-ray crystallography of the CD94 extracellular domain at 2.6 Å

    PMID:10023772

    Open questions at the time
    • Structure of the intact CD94-NKG2A heterodimer not solved
    • HLA-E contact surface inferred, not visualized
  7. 2002 Medium

    Showed the inhibitory receptor is inducible, with IL-12 driving NKG2-A/CD94 acquisition on CD8 T cells to confer a functional inhibitory receptor.

    Evidence IL-12 culture of T cells, flow cytometry, RT-PCR, redirected killing assay

    PMID:11994435

    Open questions at the time
    • Transcriptional mechanism of IL-12 induction not defined
    • Single lab
  8. 2007 High

    Resolved the assembled receptor structure, defining an asymmetric CD94-NKG2A interface in which CD94 dominates HLA-E binding.

    Evidence X-ray crystallography of CD94-NKG2A at 2.5 Å with extensive HLA-E and receptor mutagenesis

    PMID:18083576

    Open questions at the time
    • Peptide-dependent recognition basis not yet structurally explained
  9. 2008 High

    Explained peptide-dependent recognition structurally, showing peptide conformation within the HLA-E groove, not the heavy chain, dictates CD94-NKG2 affinity.

    Evidence Crystal structures of HLA-E with two distinct leader peptides at 2.5 Å

    PMID:18339401

    Open questions at the time
    • Functional hierarchy across the full repertoire of signal-peptide variants not yet quantified
  10. 2022 Medium

    Extended the axis beyond immunity, showing microglial CD94/NKG2 engages neuronal Qa-1 to regulate activity-dependent cortical plasticity.

    Evidence Mouse knockouts and in vivo blockade of CD94/NKG2-Qa-1, ocular dominance plasticity and microglial morphology assays

    PMID:35648829

    Open questions at the time
    • Intracellular signaling in microglia not dissected
    • Single lab; human relevance untested
  11. 2023 High

    Established KLRC1 as a therapeutic checkpoint by showing its knockout relieves HLA-E inhibition and improves NK cytotoxicity against HLA-E+ tumors, and quantified which signal-peptide variants drive recognition.

    Evidence CRISPR KLRC1 knockout in human NK cells with in vitro/in vivo tumor assays; systematic signal-peptide variant recognition analysis

    PMID:37264229 PMID:37675109

    Open questions at the time
    • Durability and safety of NKG2-A disruption in vivo not fully characterized
    • Compensation by NKG2C upregulation not fully resolved
  12. 2024 Medium

    Linked CD94/NKG2 to T cell exhaustion programs, showing a LAG-3-dependent circuit generates a CD94/NKG2+ exhausted CD8 T cell subset recognizing Qa-1b.

    Evidence PD-1/LAG-3 genetic deletion in mouse chronic infection, transcriptomic/phenotypic and cytotoxicity analysis with human validation

    PMID:39121847

    Open questions at the time
    • NKG2-A-specific signaling in these Tex cells not isolated from the broader circuit
    • Mechanism of receptor induction by LAG-3/TOX undefined
  13. 2025 Medium

    Demonstrated locus-directed engineering by knocking a GD2-CAR into KLRC1, simultaneously ablating NKG2-A inhibition and arming NK cells to kill HLA-E+ tumor cells.

    Evidence CRISPR-Cas9 RNP knockin, CHANGE-seq off-target analysis, in vitro cytotoxicity

    PMID:39815622

    Open questions at the time
    • In vivo efficacy and persistence not assessed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NKG2-A surface expression, ligand-affinity tuning, and competition with the activating NKG2-C receptor are integrated to set the activation threshold across diverse cell types remains incompletely defined.
  • Transcriptional and post-translational control of NKG2-A levels across cell types not mapped
  • Quantitative rules balancing inhibitory NKG2-A vs activating NKG2-C signaling in vivo unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0001618 virus receptor activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3
Partners
CD94HLA-EPTPN6 (SHP-1)
Complex memberships
CD94/NKG2-A heterodimer

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 KLRC1 (NKG2-A) encodes a type II integral membrane protein of 215-233 amino acids containing a C-type lectin domain, expressed on NK cells but not T or B cells. NKG2-A and NKG2-B are alternative splicing products of a single gene. cDNA cloning, sequence analysis, Northern blotting The Journal of experimental medicine High 2007850
1996 NKG2-A/B forms disulfide-bonded heterodimers with CD94 on NK cells. NKG2-A/B possesses two immunoreceptor tyrosine-based inhibition motif (ITIM) sequences in its cytoplasmic domain, providing the molecular basis for inhibitory receptor function. Biochemical characterization, immunoprecipitation, sequence analysis Journal of immunology High 8943374
1997 The CD94/NKG2-A inhibitory receptor complex on NK cells recognizes HLA class I molecules via NKG2-A's ITIMs. The Z199 mAb specifically recognizes NKG2-A. NKG2-B (alternatively spliced product of the NKG2-A gene) can also assemble with CD94. Both NKG2-A and NKG2-B contain cytoplasmic ITIMs. Immunoprecipitation, mAb characterization, functional cytotoxicity assays European journal of immunology High 9045931
1997 NKG2-A delivers inhibitory signals in NK cells: chimeric NKG2-A/NKR-P1C receptor inhibited lytic activity and failed to stimulate calcium response. NKG2-A-mediated inhibition is associated with selective recruitment of SHP-1 tyrosine phosphatase to the NKG2-A cytoplasmic domain. Chimeric receptor transfection into rat NK cell line (RNK-16), cytotoxicity assays, calcium flux measurements, immunoprecipitation Journal of immunology High 9103421
1997 CD94/NKG2-A inhibitory receptor complex is involved in NK cell-mediated recognition of HLA-G1; most NK clones blocked by HLA-G1 expressed CD94/NKG2-A, and CD94-specific mAbs restored cytolytic activity. NK cell clone functional assays, mAb blocking experiments, cytotoxicity assays with 721.221 transfectants Journal of immunology Medium 9190923
1997 CD94/NKG2 is the predominant inhibitory receptor for HLA-G on decidual NK cells; anti-CD94 mAb blocked recognition of HLA-G transfectants whereas KIR-specific mAbs had no effect. NK cell clone establishment from placenta, mAb blocking cytotoxicity assays Journal of immunology Medium 9233599
1997 CD94/NKG2 inhibitory receptor complex on Vγ9Vδ2 T cells inhibits proliferative and cytotoxic responses; signaling through CD94/NKG2 interferes with IFN-γ and TNF-α synthesis by these cells. Anti-CD94 mAb blocking of proliferation and cytokine production, cytotoxicity assays Journal of immunology Medium 9550399
1998 CD94/NKG2-A specifically recognizes HLA-E molecules on target cells, leading to inhibition of NK cell lysis. HLA-E surface expression requires binding of peptides from HLA class I signal sequences; only peptides with Met at position 2 confer resistance to NK lysis. CD94/NKG2-A recognition is blocked by CD94-specific (not KIR-specific) mAbs. NK cell cytotoxicity assays, peptide loading of HLA-E on 721.221 cells, mAb blocking The Journal of experimental medicine High 9480992
1998 Engagement of CD94/NKG2-A by either specific mAb (Z199) or by HLA-E+ target cells induces tyrosine phosphorylation of the NKG2-A subunit and recruitment of SHP-1 phosphatase. This mechanism was confirmed in RBL-2H3 transfectants expressing CD94/NKG2-A, where receptor cross-linking inhibited FcεRI-triggered secretory events. mAb cross-linking, immunoprecipitation, Western blotting for phosphotyrosine and SHP-1, RBL transfectant system European journal of immunology High 9565368
1998 HLA-E-bound peptides influence recognition by inhibitory CD94/NKG2-A; the primary structure of HLA-E-bound peptides modulates CD94/NKG2A-mediated recognition beyond their ability to stabilize surface HLA-E. CD94/NKG2A+ NK clones showed greater sensitivity to most HLA-E/peptide complexes compared to CD94/NKG2C+ cells. NK clone cytotoxicity assays with 721.221 cells loaded with synthetic nonamers, comparison of inhibitory vs activating receptor-expressing clones European journal of immunology Medium 9754572
1999 Soluble CD94/NKG2-A has higher binding affinity for HLA-E than activating CD94/NKG2-C. Both receptors show peptide-dependent recognition of HLA-E with very fast association and dissociation kinetics. Binding affinity of peptide-HLA-E complexes correlates directly with triggering of NK cell responses. Surface plasmon resonance (BIAcore) with soluble recombinant HLA-E and CD94/NKG2-A and CD94/NKG2-C proteins The EMBO journal High 10428963
1999 Crystal structure of CD94 extracellular domain (2.6 Å) reveals a novel C-type lectin fold with a non-functional Ca2+-binding site and modified carbohydrate-binding region. The CD94 dimer interface suggests a putative HLA-E binding region and implicates how NKG2 interacts with CD94. X-ray crystallography Immunity High 10023772
1999 CD94/NKG2-A inhibits CD16-triggered NK cell cytotoxicity by blocking tyrosine phosphorylation and activation of Syk kinase, tyrosine phosphorylation of CD16 zeta subunit, and downstream activation of ERK. Inhibition is exerted at a PTK-dependent stage upstream of p21ras, blocking Shc phosphorylation and Shc/Grb-2 complex formation. Co-engagement of CD94/NKG2-A and CD16 in primary NK cells, Western blotting for kinase phosphorylation, kinase activity assays Journal of immunology High 10358164
1999 HLA-E-mediated protection of porcine endothelial cells from human NK cells is CD94/NKG2-dependent: HLA-E engagement leads to phosphorylation of the CD94/NKG2 complex and recruitment of SHP-1. HLA-G protection operates via a CD94/NKG2-independent pathway. mAb blocking assays, phosphorylation analysis, SHP-1 co-immunoprecipitation Journal of immunology Medium 10570324
2000 CD94/NKG2-A co-engagement with CD69 suppresses CD69-triggered cell degranulation by inhibiting ERK activation in NK cells. Co-engagement of CD94/NKG2-A in RBL transfectants and human NK cells inhibited CD69-induced cytotoxicity. RBL transfectants co-expressing CD69 and CD94/NKG2-A, ERK activation assays, degranulation assays, NK cell cytotoxicity European journal of immunology Medium 10671222
2000 HLA-E is expressed on trophoblast cells and interacts with CD94/NKG2 receptors on decidual NK cells; the majority of decidual NK cells bind HLA-E tetrameric complexes in a CD94-dependent manner. The overall functional outcome of CD94/NKG2-HLA-E interaction is inhibition of decidual NK cell cytotoxicity. HLA-E tetramer staining, mAb blocking, cytotoxicity assays with polyclonal decidual NK cells European journal of immunology Medium 10898498
2000 The activating CD94/NKG2-C receptor triggers cytotoxic effector functions via activation of the MAPK/ERK pathway; MEK inhibitor PD098059 blocked CD94/NKG2-C-dependent TNF-α production and cytotoxicity. CD94/NKG2-C signals through DAP12/KARAP. MEK inhibitor (PD098059) treatment, MAPK phosphorylation assays, cytotoxicity and TNF-α production assays, RBL transfection with CD94/NKG2-C/DAP12 European journal of immunology Medium 11069065
2002 IL-12 induces expression of NKG2-A and/or CD94 on CD8+ T cells in culture, leading to acquisition of a functional inhibitory receptor, as demonstrated by redirected killing assay. This induction is not mediated by IFN-γ or IL-15. Culture of T cells with IL-12, flow cytometry, RT-PCR, redirected killing assay Journal of immunology Medium 11994435
2004 CD94/NKG2A inhibitory receptor plays a critical role in down-regulating iNKT cell responses. IFN-γ produced during alpha-GalCer stimulation upregulates Qa-1b, which in turn inhibits iNKT cell activity via CD94/NKG2A. Blockade of the CD94/NKG2-Qa-1b interaction markedly augmented iNKT cell recall and primary responses. mAb blockade of CD94/NKG2-Qa-1b interaction, alpha-GalCer stimulation assays in vivo and in vitro, flow cytometry for receptor down-modulation Blood Medium 15746081
2004 NKG2A preferential surface expression over NKG2C with CD94 is determined by a single amino acid difference in the transmembrane domain. The stalk domain of NKG2C enhances heterodimer formation with CD94. DAP12 enhances NKG2C's ability to compete for CD94 surface expression. Transfection of NKG2A/NKG2C chimeric and mutant constructs, flow cytometry for surface expression, DAP12 co-transfection Journal of immunology Medium 15153509
2007 Crystal structure of CD94-NKG2A heterodimer at 2.5 Å reveals an asymmetric dimer interface (contrasting with homodimeric NK receptors), providing structural basis for preferred heterodimeric assembly. Structure-based mutagenesis on HLA-E and CD94-NKG2A established that CD94 plays a more dominant role than NKG2A in interacting with HLA-E. X-ray crystallography at 2.5 Å, extensive mutagenesis studies on HLA-E and CD94-NKG2A Immunity High 18083576
2008 Subtle peptide conformational changes within the HLA-E binding groove, without changes in the HLA-E heavy chain, determine differential recognition by CD94-NKG2 receptors. Structures of HLA-E with HLA-Cw*07 peptide (poor CD94-NKG2 recognition) and HLA-G*01 peptide (high-affinity CD94-NKG2 ligand) both at 2.5 Å confirmed peptide-dependent recognition. X-ray crystallography at 2.5 Å of HLA-E with two different leader peptides Journal of molecular biology High 18339401
2022 In mouse cortex, CD94/NKG2 receptor is expressed by microglial cells and interacts with Qa-1 (HLA-E homolog) expressed in layer 6 corticothalamic neurons. This neuron-microglial interaction via the Qa-1/CD94/NKG2 axis regulates activity-dependent plasticity in the visual cortex; selectively targeting this interaction phenocopies plasticity perturbation seen in Qa-1 knockouts. Mouse knockouts, in vivo pharmacological blockade of CD94/NKG2-Qa-1 interaction, ocular dominance plasticity assays, microglial morphology analysis Proceedings of the National Academy of Sciences of the United States of America Medium 35648829
2023 KLRC1 knockout in human NK cells relieves HLA-E-mediated inhibition and significantly improves cytotoxicity against HLA-E+ solid tumor cell lines in vitro and delays tumor progression in vivo. KLRC1 KO also increases NKG2C expression on NK cells. CRISPR-mediated KLRC1 gene editing, in vitro cytotoxicity assays against multiple HLA-E+ tumor lines, xenogeneic mouse model of metastatic breast cancer Frontiers in immunology High 37675109
2023 Antigen-specific human NK cell memory against HIV and influenza is largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E, as demonstrated by single-cell cloning of memory NK cells and identification of individual HLA-E-restricted peptides. Single-cell NK cell cloning, complex immunophenotyping, peptide-HLA-E tetramer assays, functional memory NK cell assays Science immunology Medium 38064568
2023 Among 16 common classical HLA class I signal peptide variants, only 6 efficiently generate epitopes enabling CD94/NKG2 engagement. HLA-B/-21M SP induces high HLA-E expression but confers the lowest receptor recognition, competing with other SPs for HLA-E epitope binding and reducing overall CD94/NKG2A recognition of target cells. Systematic quantitative analysis of signal peptide processing, HLA-E surface expression assays, CD94/NKG2A recognition assays with multiple peptide variants Nature immunology High 37264229
2024 LAG-3 sustains TOX expression and controls a LAG-3-dependent circuit generating a CD94/NKG2+ subset of exhausted CD8 T cells with enhanced cytotoxicity mediated by recognition of the stress ligand Qa-1b (mouse homolog of HLA-E). Loss of LAG-3 reduces this CD94/NKG2+ Tex subset. Genetic deletion of PD-1 and/or LAG-3 in mouse chronic viral infection model, transcriptomic and phenotypic analysis, functional cytotoxicity assays, validation in human samples Cell Medium 39121847
2025 CRISPR-Cas9 knockin of a GD2-CAR into the KLRC1 locus in human NK cells simultaneously disrupts NKG2A inhibitory signaling (98% KO efficiency) and introduces GD2-targeting CAR, generating NK cells that overcome HLA-E-based inhibition and kill GD2+ HLA-E-expressing melanoma cells. CRISPR-Cas9 ribonucleoprotein-mediated knockin, CHANGE-seq off-target analysis, in vitro cytotoxicity assays Molecular therapy Medium 39815622

Source papers

Stage 0 corpus · 88 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 571 9480992
1991 DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells. The Journal of experimental medicine 390 2007850
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 301 10428963
2000 HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. European journal of immunology 290 10898498
1997 The CD94 and NKG2-A C-type lectins covalently assemble to form a natural killer cell inhibitory receptor for HLA class I molecules. European journal of immunology 251 9045931
1997 Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. Journal of immunology (Baltimore, Md. : 1950) 186 9103421
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
2006 The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunologic research 119 17172651
1999 Structure of CD94 reveals a novel C-type lectin fold: implications for the NK cell-associated CD94/NKG2 receptors. Immunity 111 10023772
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
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
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
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
2008 Subtle changes in peptide conformation profoundly affect recognition of the non-classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell receptors. Journal of molecular biology 88 18339401
2024 LAG-3 sustains TOX expression and regulates the CD94/NKG2-Qa-1b axis to govern exhausted CD8 T cell NK receptor expression and cytotoxicity. Cell 86 39121847
2007 The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition. Immunity 82 18083576
2011 Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae experimentalis 81 21800130
2005 Switch from inhibitory to activating NKG2 receptor expression in HIV-1 infection: lack of reversion with highly active antiretroviral therapy. AIDS (London, England) 81 16227783
2019 NKG2D/NKG2-Ligand Pathway Offers New Opportunities in Cancer Treatment. Frontiers in immunology 75 30984204
2002 Conservation and variation in human and common chimpanzee CD94 and NKG2 genes. Journal of immunology (Baltimore, Md. : 1950) 71 11751968
2000 CD69-triggered ERK activation and functions are negatively regulated by CD94 / NKG2-A inhibitory receptor. European journal of immunology 59 10671222
2023 HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses. Nature immunology 57 37264229
2002 Expression of CD94/NKG2-A on human T lymphocytes is induced by IL-12: implications for adoptive immunotherapy. Journal of immunology (Baltimore, Md. : 1950) 57 11994435
2005 Opposing effect of IFNgamma and IFNalpha on expression of NKG2 receptors: negative regulation of IFNgamma on NK cells. International immunopharmacology 55 15829421
2023 Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis. Science immunology 54 38064568
1999 HLA-E and HLA-G expression on porcine endothelial cells inhibit xenoreactive human NK cells through CD94/NKG2-dependent and -independent pathways. Journal of immunology (Baltimore, Md. : 1950) 51 10570324
1997 Cloning of NKG2-F, a new member of the NKG2 family of human natural killer cell receptor genes. European journal of immunology 49 9394807
2002 Expression of inhibitory receptors Ly49E and CD94/NKG2 on fetal thymic and adult epidermal TCR V gamma 3 lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 47 11907085
2001 Expression of Ly49E and CD94/NKG2 on fetal and adult NK cells. Journal of immunology (Baltimore, Md. : 1950) 47 11254682
2005 IFN-gamma-mediated negative feedback regulation of NKT-cell function by CD94/NKG2. Blood 46 15746081
2003 Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population. Genes and immunity 46 12618865
1998 Two genes in the rat homologous to human NKG2. European journal of immunology 45 9521051
2001 The KIR and CD94/NKG2 families of molecules in the rhesus monkey. Immunological reviews 44 11782245
2001 Ly49 and CD94/NKG2: developmentally regulated expression and evolution. Immunological reviews 42 11513155
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
2023 KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors. Frontiers in immunology 35 37675109
2002 Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro. Journal of immunology (Baltimore, Md. : 1950) 33 11994449
2002 CD94/NKG2 expression does not inhibit cytotoxic function of lymphocytic choriomeningitis virus-specific CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950) 33 12097371
2002 NK cells developing in vitro from fetal mouse progenitors express at least one member of the Ly49 family that is acquired in a time-dependent and stochastic manner independently of CD94 and NKG2. European journal of immunology 32 11870631
2007 Chicken CD69 and CD94/NKG2-like genes in a chromosomal region syntenic to mammalian natural killer gene complex. Immunogenetics 31 17505822
2002 Differential expression of inhibitory and activating CD94/NKG2 receptors on NK cell clones. Journal of immunological methods 31 12191515
1999 Linkage of the NKG2 and CD94 receptor genes to D12S77 in the human natural killer gene complex. Immunogenetics 29 9887346
2001 Expression of CD94 and NKG2 molecules on human CD4(+) T cells in response to CD3-mediated stimulation. Journal of leukocyte biology 28 11493613
1995 NKG2-C is a receptor on human natural killer cells that recognizes structures on K562 target cells. European journal of immunology 28 7589093
2010 Cytotoxic T cells expressing the co-stimulatory receptor NKG2 D are increased in cigarette smoking and COPD. Respiratory research 24 20863413
2007 Differential induction of CD94 and NKG2 in CD4 helper T cells. A consequence of influenza virus infection and interferon-gamma? Immunology 24 17462078
2002 Cutting edge: CD94/NKG2 is expressed on Th1 but not Th2 cells and costimulates Th1 effector functions. Journal of immunology (Baltimore, Md. : 1950) 23 12421909
2000 Expression of CD94/NKG2 subtypes on tumor-infiltrating lymphocytes in primary and metastatic melanoma. The Journal of investigative dermatology 23 10771475
2000 Differential expression of CD28 and CD94/NKG2 on T cells with identical TCR beta variable regions in primary melanoma and sentinel lymph node. European journal of immunology 21 11169413
2016 Diversification of both KIR and NKG2 natural killer cell receptor genes in macaques - implications for highly complex MHC-dependent regulation of natural killer cells. Immunology 19 27565739
2006 NKG2 receptor-mediated regulation of effector CTL functions in the human tissue microenvironment. Current topics in microbiology and immunology 19 16323414
2000 The NKG2 natural killer cell receptor family: comparative analysis of promoter sequences. Genes and immunity 19 11197693
2007 Complexity in the cattle CD94/NKG2 gene families. Immunogenetics 18 17285285
2020 The murine CD94/NKG2 ligand, Qa-1b, is a high-affinity, functional ligand for the CD8αα homodimer. The Journal of biological chemistry 17 31992596
2025 Virus-free CRISPR knockin of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells. Molecular therapy : the journal of the American Society of Gene Therapy 14 39815622
2004 Persistent expression of CD94/NKG2 receptors by virus-specific CD8 T cells is initiated by TCR-mediated signals. International immunology 14 15302848
2002 Differential expression of inhibitory or activating CD94/NKG2 subtypes on MART-1-reactive T cells in vitiligo versus melanoma: a case report. The Journal of investigative dermatology 14 11918704
2000 The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region. Genes and immunity 14 11196705
2015 Up-regulation of activating and inhibitory NKG2 receptors in allogeneic and autologous hematopoietic stem cell grafts. Journal of experimental & clinical cancer research : CR 13 26361968
2004 Molecular determinants regulating the pairing of NKG2 molecules with CD94 for cell surface heterodimer expression. Journal of immunology (Baltimore, Md. : 1950) 13 15153509
2001 Homologues of natural killer cell receptors NKG2-D and NKR-P1 expressed in cattle. Veterinary immunology and immunopathology 13 11457486
2000 Mitogen-activated protein kinase activity is involved in effector functions triggered by the CD94/NKG2-C NK receptor specific for HLA-E. European journal of immunology 13 11069065
2022 The nonclassical MHC class I Qa-1 expressed in layer 6 neurons regulates activity-dependent plasticity via microglial CD94/NKG2 in the cortex. Proceedings of the National Academy of Sciences of the United States of America 12 35648829
2004 Variable NKG2 expression in the peripheral blood lymphocytes of rhesus monkeys. Clinical and experimental immunology 12 15498028
2002 A case of lymphoblastoid natural killer (NK)-cell lymphoma: association with the NK-cell receptor complex CD94/NKG2 and TP53 intragenic deletion. The British journal of dermatology 12 11841384
1997 The CD94/NKG2 C-type lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules. Immunologic research 12 9212363
2024 A role of gut microbiota metabolites in HLA-E and NKG2 blockage immunotherapy against tumors: new insights for clinical application. Frontiers in immunology 9 39229258
2005 Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-beta receptor expression. Blood 8 15827137
2004 Role for NKG2-A and NKG2-C surface receptors in chronic CD4+ T-cell responses. Immunology and cell biology 8 15550116
2000 Natural killer cell surveillance of intracellular antigen processing pathways mediated by recognition of HLA-E and Qa-1b by CD94/NKG2 receptors. Microbes and infection 8 10817639
1999 Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells. Scandinavian journal of immunology 7 10320637
2023 Significance of HLA-E and its two NKG2 receptors in development of complications after allogeneic transplantation of hematopoietic stem cells. Frontiers in immunology 6 37901227
2022 Characterization of NKG2-A/-C, Kir and CD57 on NK Cells Stimulated with pp65 and IE-1 Antigens in Patients Awaiting Lung Transplant. Life (Basel, Switzerland) 6 35888169
2019 Haplotype block 1 variant (HB-1v) of the NKG2 family of receptors. Human immunology 6 31320124
1999 N-linked oligosaccharides can protect target cells from the lysis mediated by NK cells but not by cytotoxic T lymphocytes: role of NKG2-A. Tissue antigens 6 10488737
2025 The Association of HLA-E Ligand and NKG2 Receptor Variation With Relapse and Mortality After Haploidentical Related Donor Transplantation. Transplantation and cellular therapy 4 39798802
2023 Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder. Journal of neuroimmunology 4 37352688
2025 Molecular characterization and functional prioritization of CD46, IL6R, KLRC1, LEAP2 and SMOX as candidate targets in acute kidney injury. International journal of biological macromolecules 3 40683494
2024 DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis: Perspective of Different Water Iodine Exposure. Biomedical and environmental sciences : BES 3 39401997
2007 [Identification of a novel candidate gene KLRC1 within the putative susceptibility locus for systemic lupus erythematosus at 12p12.3-13.2 in a Chinese cohort]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 1 17545086
2007 Variation in the ligand binding domains of the CD94/NKG2 family of receptors in the squirrel monkey. Immunogenetics 1 17896104
2026 Tumor-intrinsic KLRC1 exerts tumor-suppressive functions in colorectal cancer. Discover oncology 0 41811633
2025 Genetic Variability in NKG2 Receptors and Their Ligands: Associations with SARS-CoV-2 Infection and COVID-19 Severity. Genes 0 41153412
2024 Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells. bioRxiv : the preprint server for biology 0 38405747

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