Affinage

KLRC2

NKG2-C type II integral membrane protein · UniProt P26717

Length
231 aa
Mass
26.2 kDa
Annotated
2026-06-10
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLRC2 (NKG2C) encodes a C-type lectin-like type II transmembrane receptor that pairs with CD94 to form an activating NK-cell receptor recognizing the non-classical MHC class Ib molecule HLA-E (and its murine homolog Qa-1b) in a peptide-dependent manner (PMID:9485212, PMID:10428963, PMID:10601355). Unlike its inhibitory counterpart CD94/NKG2A, CD94/NKG2C does not recruit the phosphatase SHP-1 but instead associates non-covalently with the ITAM-bearing adapter DAP12 through reciprocal charged transmembrane residues, an interaction also required for efficient surface expression of the complex (PMID:9103421, PMID:9655483). Receptor engagement signals through DAP12 to drive MAPK/ERK phosphorylation and calcium mobilization, triggering cytotoxicity and cytokine production (PMID:11069065); CD94/NKG2A and CD94/NKG2C engage overlapping but distinct epitopes on the HLA-E α1/α2 surface, with NKG2C binding at lower affinity and the response magnitude scaling with peptide-HLA-E binding strength (PMID:10428963, PMID:14971033). Beyond NK cells, functional DAP12-coupled CD94/NKG2C operates on subsets of CD8+ T and Vδ2 γδ T cells, mediating TCR-independent effector activity, with NKG2A signaling dominating when both receptors are co-expressed (PMID:15940674, PMID:20952657, PMID:35644434). HCMV infection drives clonal expansion of NKG2C+ NK cells in a manner requiring CD94/NKG2C–HLA-E engagement plus IL-12 and IL-15, generating adaptive memory-like NK cells; these adaptive features can also arise in NKG2C-deficient individuals through CD2-dependent co-stimulation (PMID:16384928, PMID:25384219, PMID:27117418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1995 Medium

    Established that NKG2-C is a cell-surface glycoprotein capable of binding specific target cells, linking receptor expression to NK target recognition.

    Evidence Recombinant soluble NKG2-C binding assays across hematopoietic cell lines with phorbol-ester differentiation of K562

    PMID:7589093

    Open questions at the time
    • Ligand identity unknown at this stage
    • No signaling mechanism defined
  2. 1997 High

    Distinguished NKG2-C from inhibitory NKG2-A by showing it delivers an activating rather than inhibitory signal, settling its functional polarity.

    Evidence Chimeric NKG2-C/NKR-P1C receptor transfection in rat NK cells with cytotoxicity, calcium flux, and SHP-1 co-IP

    PMID:9103421

    Open questions at the time
    • Adapter mediating activation not yet identified
    • Native ligand not defined
  3. 1998 High

    Identified the molecular basis of activation by showing CD94/NKG2C associates with the ITAM adapter DAP12 via transmembrane charged residues, explaining how an activating signal is transduced.

    Evidence Co-immunoprecipitation and transmembrane-domain mutagenesis; COS7 co-transfection and redirected killing

    PMID:9485212 PMID:9655483

    Open questions at the time
    • Downstream signaling cascade not yet mapped
    • Affinity/kinetics of ligand binding unmeasured
  4. 1999 High

    Defined HLA-E (and Qa-1b in mouse) as the peptide-dependent ligand and quantified that NKG2C binds at lower affinity than NKG2A, establishing the ligand recognition logic.

    Evidence Surface plasmon resonance with recombinant peptide-loaded HLA-E; mouse receptor cloning and antibody blockade

    PMID:10428963 PMID:10601355

    Open questions at the time
    • Structural basis of differential affinity not resolved
    • Physiologic peptide repertoire incompletely defined
  5. 2000 High

    Mapped the activating signal to the MAPK/ERK and calcium pathways, connecting DAP12 engagement to effector output.

    Evidence MEK inhibitor blockade, phospho-MAPK Western blot, calcium and serotonin release in transfected RBL cells

    PMID:11069065

    Open questions at the time
    • Proximal kinases linking DAP12 to ERK not identified here
  6. 2004 High

    Showed NKG2A and NKG2C use overlapping but partly distinct HLA-E epitopes, explaining how the two receptors discriminate the same ligand.

    Evidence Alanine-scanning mutagenesis of HLA-E with soluble receptor binding assays

    PMID:14971033

    Open questions at the time
    • No co-crystal structure of NKG2C–HLA-E
  7. 2005 High

    Extended functional CD94/NKG2C–DAP12 signaling to CD8+ T cells, showing TCR-independent activation of cytotoxicity and proliferation.

    Evidence Reciprocal DAP12 co-IP, HLA-E transfectant co-culture, and functional assays in CD8+ T cell clones

    PMID:15940674

    Open questions at the time
    • In vivo relevance of T-cell NKG2C not established
  8. 2005 High

    Identified the determinants of HCMV-driven NKG2C+ NK cell expansion, requiring receptor engagement of infected cells and IL-15.

    Evidence Co-culture with HCMV-infected fibroblasts, viral deletion mutants, anti-CD94 blockade, IL-15 supplementation

    PMID:16384928

    Open questions at the time
    • Specific viral/host ligand driving expansion not pinpointed
    • Role of US2-11 region mechanistically unresolved
  9. 2009 Medium

    Revealed a regulatory loop whereby IL-12 induces inhibitory NKG2A on NKG2C+ cells, dampening their cytolytic activity.

    Evidence In vitro stimulation, anti-IL-12 neutralization, cytolytic assays with HLA-E transfectants

    PMID:19124726

    Open questions at the time
    • Single lab
    • Durability and in vivo significance of induced NKG2A unclear
  10. 2010 Medium

    Demonstrated functional CD94/NKG2C–DAP12 in Vδ2 γδ T cells and established NKG2A dominance over NKG2C in co-expressing cells.

    Evidence Functional assays (IFN-γ, proliferation, cytolysis) in primary γδ T cells

    PMID:20952657

    Open questions at the time
    • Single lab
    • Mechanism of NKG2A dominance over NKG2C not resolved
  11. 2012 Medium

    Refined the atomic architecture of the DAP12–NKG2C transmembrane interface, defining the salt-bridge/hydrogen-bond network underlying complex assembly.

    Evidence NMR-constrained molecular dynamics in explicit membranes

    PMID:22500771

    Open questions at the time
    • Computational refinement without new mutagenesis validation in this study
  12. 2013 Medium

    Showed NKG2C gene dosage quantitatively tunes receptor levels and effector responses, linking genotype to functional output.

    Evidence Functional assays (calcium, CD107a, IL-15 proliferation) in NKG2C copy-number-stratified cohort

    PMID:24030638

    Open questions at the time
    • Single lab
    • Mechanism connecting zygosity to per-cell response not dissected
  13. 2014 High

    Defined IL-12 from inflammatory monocytes plus HLA-E/NKG2C engagement as jointly required for HCMV-driven NKG2C+ expansion, integrating innate cytokine and receptor signals.

    Evidence Co-culture with infected fibroblasts and monocytes, IL-12 neutralization, receptor blockade, HLA-E siRNA

    PMID:25384219

    Open questions at the time
    • Transcriptional program downstream of these signals not mapped
  14. 2015 Medium

    Showed HLA-E peptide identity governs NKG2C+ degranulation and that engagement triggers receptor internalization, revealing peptide-restricted activation control.

    Evidence Peptide-loaded targets, CD107a assay, surface NKG2C measurement with bafilomycin rescue

    PMID:26382247

    Open questions at the time
    • Single lab
    • In vivo relevance of HLA-G-derived peptide restriction unclear
  15. 2016 High

    Demonstrated that adaptive NK features can develop independent of NKG2C, with CD2 providing co-stimulatory signal 2 for antibody-driven responses.

    Evidence Repertoire and phospho-flow (ERK, S6RP), ADCC, and IFN-γ epigenetics in 60 NKG2C-/- donors

    PMID:27117418

    Open questions at the time
    • Relative contribution of NKG2C versus CD2 in NKG2C-sufficient individuals unresolved
  16. 2017 Medium

    Showed HCMV strain dependence of NKG2C activation and evidence for a non-canonical ligand beyond HLA-E.

    Evidence Jurkat-NKG2C/DAP12 NFAT/AP1-luciferase reporter with multiple viral strains and antibody blockade

    PMID:29114247

    Open questions at the time
    • Identity of the antibody-resistant ligand unknown
    • Single lab
  17. 2019 Medium

    Revealed an unexpected antigen-presenting function of HLA-DR+ NKG2C+ adaptive NK cells, activating CD4+ T cells against HCMV antigen.

    Evidence NK–T cell co-culture, HLA-DR blockade, cytokine/CD107a flow cytometry

    PMID:31001281

    Open questions at the time
    • Single lab
    • In vivo contribution of NK antigen presentation unproven
  18. 2022 Medium

    Extended TCR-independent NKG2C effector function to tissue-resident liver CD8+ T cells, broadening the receptor's role in tissue immunity.

    Evidence CITE-seq with TCR-seq and NKG2C ligation functional assays in liver perfusate cells

    PMID:35644434

    Open questions at the time
    • Single lab
    • Physiologic ligand engaging these cells in liver not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the non-canonical, antibody-resistant ligand engaged by CD94/NKG2C on certain HCMV-infected cells remains unresolved, as does the structural basis of NKG2C versus NKG2A discrimination of peptide-HLA-E.
  • No co-crystal structure of NKG2C bound to HLA-E
  • Non-HLA-E ligand uncharacterized
  • Mechanism of viral strain-specific activation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0001618 virus receptor activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2
Partners
CD94DAP12HLA-E
Complex memberships
CD94/NKG2C-DAP12 receptor complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NKG2-C delivers an activating transmembrane signal in NK cells: chimeric NKG2-C/NKR-P1C receptors stimulated lytic activity and calcium mobilization when cross-linked, and the inhibitory tyrosine phosphatase SHP-1 did NOT associate with the NKG2-C chimeric receptor (in contrast to the inhibitory NKG2-A chimeric receptor). Chimeric receptor transfection in RNK-16 rat NK cells; cytolytic assays; calcium mobilization assays; immunoprecipitation Journal of immunology High 9103421
1998 CD94/NKG2C forms a non-covalent complex with the ITAM-bearing adapter DAP12; charged residues in the transmembrane domains of both DAP12 and NKG2C are required for this interaction, and DAP12 is necessary for efficient surface expression of CD94/NKG2C. Co-immunoprecipitation; cell-surface expression analysis with transmembrane domain mutants Immunity High 9655483
1998 The 39-kDa protein (Kp39) co-precipitated with CD94 from NKG2A-negative NK cells is covalently associated with CD94 and is the product of the NKG2-C gene; co-transfection of CD94 and NKG2-C in COS7 cells confirmed the identity of Kp39 as NKG2-C, and engagement of the complex by a specific mAb triggered redirected cytotoxicity. Immunoprecipitation; COS7 co-transfection; peptide mapping; RT-PCR on NK clones; redirected killing assay European journal of immunology High 9485212
1999 Both CD94/NKG2-A and CD94/NKG2-C bind HLA-E in a peptide-dependent manner; CD94/NKG2-A has higher binding affinity for HLA-E than CD94/NKG2-C, and both receptors show very fast association and dissociation kinetics. The magnitude of NK cell response correlates directly with the binding affinity of peptide-HLA-E complexes for the receptors. Surface plasmon resonance (kinetic binding analysis) using soluble recombinant HLA-E and recombinant soluble receptor proteins assembled with defined peptides The EMBO journal High 10428963
1999 Mouse CD94/NKG2C and CD94/NKG2E bind the MHC class Ib molecule Qa-1(b); a blocking anti-NKG2 monoclonal antibody demonstrated that CD94/NKG2 molecules are the only Qa-1(b) receptors on mouse NK cells. Cloning and expression; binding assay; anti-NKG2 blocking antibody The Journal of experimental medicine High 10601355
2000 Engagement of CD94/NKG2C on an NK clone induces MAPK (ERK) phosphorylation; the MEK inhibitor PD098059 blocks CD94-dependent TNF-α production and cytotoxicity. In RBL cells transfected with CD94/NKG2C/DAP12, receptor cross-linking induces calcium mobilization, serotonin release, and MAPK phosphorylation. Pharmacological inhibition (MEK inhibitor); Western blot for phospho-MAPK; calcium mobilization; serotonin release assay in transfected RBL cells European journal of immunology High 11069065
2004 CD94/NKG2A and CD94/NKG2C recognize an overlapping but partly distinct set of residues on the top of HLA-E (α1/α2 domain); two HLA-E mutations (D69A and H155A) selectively abrogated binding to CD94/NKG2A without substantially affecting CD94/NKG2C binding, demonstrating differential epitope usage. Alanine-scanning mutagenesis of HLA-E; binding assay with soluble CD94/NKG2A and CD94/NKG2C European journal of immunology High 14971033
2005 CD94/NKG2C is expressed on a subset of CD8+ T cells (and rare TCRγδ+ and CD4+ cells) and is coupled to DAP12 in these T cells; selective engagement of CD94/NKG2C triggers cytotoxicity, cytokine production, IL-2Rα upregulation, and proliferation in CD8+ T cell clones independently of TCR. Co-immunoprecipitation of DAP12 with anti-CD94; co-culture with HLA-E transfectants; mAb engagement; proliferation assays; cytokine assays; cytotoxicity assays European journal of immunology High 15940674
2005 Expansion of CD94/NKG2C+ NK cells in response to HCMV-infected fibroblasts requires interaction of CD94/NKG2C with the infected cells (blocked by anti-CD94 mAb) and requires IL-15 for proliferation; this expansion is independent of HCMV genes UL16, UL18, and UL40 but is impaired by deletion of the US2-11 gene region. Co-culture with HCMV-infected fibroblasts and deletion mutant viruses; anti-CD94 antibody blockade; IL-15 supplementation; flow cytometry Blood High 16384928
2009 IL-12 induces transient expression of the inhibitory CD94/NKG2A receptor on CD94/NKG2C+ NK cells; this inducible NKG2A inhibits the cytolytic activity of NKG2C+ NK clones upon engagement by HLA-E. Anti-IL-12 antibody prevented this NKG2A upregulation in HCMV-infected DC co-cultures. In vitro NK cell stimulation; anti-IL-12 mAb neutralization; flow cytometry; cytolytic assays with HLA-E transfectants; NK clones Journal of immunology Medium 19124726
2012 NMR-based structure refinement of the DAP12-NKG2C transmembrane helix complex in explicit membranes reveals that five functionally required interfacial residues (two Asp and two Thr in DAP12 dimer; one Lys in NKG2C) form a stable network of salt bridges and hydrogen bonds; the arrangement is energetically consistent with experimental observations. NMR observable-constrained molecular dynamics simulation in explicit micelles and bilayers Biophysical journal Medium 22500771
2014 IL-12 produced by CD14+ inflammatory monocytes, combined with HLA-E/CD94-NKG2C engagement, is required for expansion of NKG2C+ NK cells in response to HCMV infection; IL-12 neutralization substantially reduced CD25 upregulation and NKG2C+ subset expansion; blockade of CD94/NKG2C or silencing of HLA-E greatly impaired NKG2C+ NK cell expansion. Co-culture system with HCMV-infected fibroblasts and monocytes; IL-12 neutralization; anti-CD94/NKG2C blocking antibody; HLA-E siRNA silencing; flow cytometry The Journal of clinical investigation High 25384219
2013 NKG2C zygosity quantitatively influences surface CD94/NKG2C receptor levels, NKG2C+ NK cell numbers, calcium influx, degranulation, and IL-15-dependent proliferation in response to NKG2C engagement; NKG2C+/+ individuals show greater responses than hemizygous NKG2C+/del individuals. Flow cytometry; intracellular calcium measurement; degranulation assay (CD107a); IL-15-driven proliferation assay in cohort stratified by NKG2C copy number European journal of immunology Medium 24030638
2015 HLA-E regulates NKG2C+ NK cell degranulation in a peptide-restricted manner: peptide-stabilized HLA-E activates NKG2A-NKG2C+ NK cells only with a restricted subset of peptides (CMV-I, A80, B13, and especially HLA-G-derived peptide), and HLA-E/G peptide complex triggers NKG2C receptor internalization (reversible with bafilomycin). Peptide-loading of target cells; CD107a degranulation assay; flow cytometric measurement of NKG2C surface expression; bafilomycin rescue Human immunology Medium 26382247
2016 In NKG2C-deficient (homozygous deletion) humans, adaptive NK cells still expand and display characteristic adaptive features (terminal differentiation, functional reprogramming, IFN-γ promoter epigenetic remodeling); these cells express high levels of CD2, which synergistically enhances ERK and S6RP phosphorylation after CD16 ligation, demonstrating that CD2 provides co-stimulatory 'signal 2' for antibody-driven adaptive NK cell responses independent of NKG2C. NK cell repertoire analysis in 60 NKG2C-/- donors; phospho-flow cytometry (ERK, S6RP); ADCC functional assays; epigenetic analysis of IFN-γ promoter Cell reports High 27117418
2010 The CD94/NKG2C complex, associated with KARAP/DAP12, is fully functional in γδ T cells (Vδ2 subset), triggering IFN-γ production, proliferation, and cytolytic activity; when NKG2A and NKG2C are co-expressed on the same cell, the inhibitory signal from NKG2A prevails over NKG2C-mediated activation. Flow cytometry; IFN-γ ELISA; proliferation assay; cytolytic assays; functional comparison in NKG2A/NKG2C double-positive cells Journal of leukocyte biology Medium 20952657
2017 CD94/NKG2C activation by HCMV-infected cells is stimulus-dependent on the virus strain: infection with laboratory strains (AD169, Towne) failed to activate a Jurkat-NKG2C reporter system despite preserving surface HLA-E, whereas clinical isolates and the endotheliotropic TB40/E strain triggered reporter activation; the TB40/E-driven response was not blocked by anti-NKG2C or anti-HLA-E antibodies, suggesting a non-canonical or additional ligand. Jurkat reporter cell line expressing CD94/NKG2C/DAP12 with NFAT/AP1-luciferase reporter; HCMV infection with multiple strains; antibody blockade of NKG2C and HLA-E Frontiers in immunology Medium 29114247
2019 NKG2C+ adaptive NK cells expressing HLA-DR can process and present HCMV antigen to autologous CD4+ T cells in an HLA-DR-dependent manner, activating polyfunctional effector-memory CD4+ T cells (CD107a+, IFN-γ+, TNF-α+) with cytotoxic potential; HCMV complexed with specific antibodies upregulates surface HLA-DR on NK cells via CD16. Purified NK cell-T cell co-culture; HLA-DR blocking antibody; flow cytometry for CD107a, IFN-γ, TNF-α; HLA-DR upregulation after antibody-complexed antigen loading Frontiers in immunology Medium 31001281
2022 In liver sinusoidal CD56hiCD161-CD8+ T cells, NKG2C mediates NK-like effector functions (degranulation and cytotoxicity) in a TCR-independent manner; these cells express CD94, KIRs, and NKG2C, and respond to NKG2C ligation without TCR stimulation. CITE-seq with TCR-seq; flow cytometry; functional assays with NKG2C ligation in absence of TCR stimulation; liver perfusate from transplant donors Journal of hepatology Medium 35644434
1995 NKG2-C is expressed as a 36-kDa glycoprotein (protein backbone ~26 kDa) on NK cells; a recombinant soluble NKG2-C specifically binds K562 and RPMI 8866 cells but not other hematopoietic cell lines; this binding is lost when K562 cells differentiate with phorbol ester/Ca2+ ionophore, concurrent with loss of susceptibility to NK killing. In vitro translation; recombinant expression; immunoprecipitation; binding assay with soluble NKG2-C on multiple cell lines; differentiation of K562 with phorbol ester European journal of immunology Medium 7589093

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood 526 22180440
1998 Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity 432 9655483
2005 Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood 356 16384928
2012 Human cytomegalovirus (CMV)-induced memory-like NKG2C(+) NK cells are transplantable and expand in vivo in response to recipient CMV antigen. Journal of immunology (Baltimore, Md. : 1950) 310 23077239
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
2011 CMV drives clonal expansion of NKG2C+ NK cells expressing self-specific KIRs in chronic hepatitis patients. European journal of immunology 241 22105371
2006 Human cytomegalovirus infection is associated with increased proportions of NK cells that express the CD94/NKG2C receptor in aviremic HIV-1-positive patients. The Journal of infectious diseases 204 16741880
2016 Critical Role of CD2 Co-stimulation in Adaptive Natural Killer Cell Responses Revealed in NKG2C-Deficient Humans. Cell reports 192 27117418
2015 CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT. Leukemia 187 26416461
1997 Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. Journal of immunology (Baltimore, Md. : 1950) 186 9103421
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 167 10601355
2014 IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. The Journal of clinical investigation 159 25384219
2014 Cutting edge: NKG2C(hi)CD57+ NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. Journal of immunology (Baltimore, Md. : 1950) 152 24740502
2014 Human cytomegalovirus infection promotes rapid maturation of NK cells expressing activating killer Ig-like receptor in patients transplanted with NKG2C-/- umbilical cord blood. Journal of immunology (Baltimore, Md. : 1950) 145 24442432
2010 Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection. AIDS (London, England) 123 19910789
2021 Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19. Genetics in medicine : official journal of the American College of Medical Genetics 105 33500568
2014 The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Seminars in immunology 94 24666761
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
2014 Rapid NK cell differentiation in a population with near-universal human cytomegalovirus infection is attenuated by NKG2C deletions. Blood 86 25150297
1998 The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex. Immunogenetics 84 9683661
2012 Influence of congenital human cytomegalovirus infection and the NKG2C genotype on NK-cell subset distribution in children. European journal of immunology 81 22965785
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
2013 NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus. European journal of immunology 76 24030638
2005 The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells. European journal of immunology 74 15940674
2013 Cytotoxic NKG2C+ CD4 T cells target oligodendrocytes in multiple sclerosis. Journal of immunology (Baltimore, Md. : 1950) 73 23396942
2002 Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors. Blood 73 12480700
2004 Molecular genetic analyses of human NKG2C (KLRC2) gene deletion. International immunology 68 14688071
2009 IL-12-dependent inducible expression of the CD94/NKG2A inhibitory receptor regulates CD94/NKG2C+ NK cell function. Journal of immunology (Baltimore, Md. : 1950) 65 19124726
2016 Relationship of NKG2C Copy Number with the Distribution of Distinct Cytomegalovirus-Induced Adaptive NK Cell Subsets. Journal of immunology (Baltimore, Md. : 1950) 64 26994220
2012 NKG2C deletion is a risk factor of HIV infection. AIDS research and human retroviruses 62 22074011
2008 NKG2C is a major triggering receptor involved in the V[delta]1 T cell-mediated cytotoxicity against HIV-infected CD4 T cells. AIDS (London, England) 58 18097224
2007 Natural killer cells in perinatally HIV-1-infected children exhibit less degranulation compared to HIV-1-exposed uninfected children and their expression of KIR2DL3, NKG2C, and NKp46 correlates with disease severity. Journal of immunology (Baltimore, Md. : 1950) 58 17709553
2016 NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection. Journal of immunology (Baltimore, Md. : 1950) 56 28031335
2016 Adaptive NKG2C+ NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients. Journal of immunology (Baltimore, Md. : 1950) 55 27913630
2006 Expression patterns of lectin-like natural killer receptors, inhibitory CD94/NKG2A, and activating CD94/NKG2C on decidual CD56bright natural killer cells differ from those on peripheral CD56dim natural killer cells. Journal of reproductive immunology 55 16488482
2015 HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire. Human immunology 54 26382247
2004 Activating CD94:NKG2C and inhibitory CD94:NKG2A receptors are expressed by distinct subsets of committed CD8+ TCR alphabeta lymphocytes. European journal of immunology 54 15517612
2015 Activating KIRs and NKG2C in Viral Infections: Toward NK Cell Memory? Frontiers in immunology 53 26617607
2017 NKG2C+ memory-like NK cells contribute to the control of HIV viremia during primary infection: Optiprim-ANRS 147. Clinical & translational immunology 51 28791125
2010 CD94/NKG2C is a killer effector molecule in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. The Journal of allergy and clinical immunology 51 20132973
2013 Amplified NKG2C+ NK cells in cytomegalovirus (CMV) infection preferentially express killer cell Ig-like receptor 2DL: functional impact in controlling CMV-infected dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 50 23918974
2017 NKG2C+NKG2A- Natural Killer Cells are Associated with a Lower Viral Set Point and may Predict Disease Progression in Individuals with Primary HIV Infection. Frontiers in immunology 49 28979268
2022 Adaptive single-KIR+NKG2C+ NK cells expanded from select superdonors show potent missing-self reactivity and efficiently control HLA-mismatched acute myeloid leukemia. Journal for immunotherapy of cancer 47 36319065
2003 Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population. Genes and immunity 46 12618865
2019 Human Cytomegalovirus Antigen Presentation by HLA-DR+ NKG2C+ Adaptive NK Cells Specifically Activates Polyfunctional Effector Memory CD4+ T Lymphocytes. Frontiers in immunology 45 31001281
2012 Spotlight on NKG2C and the human NK-cell response to CMV infection. European journal of immunology 43 23255011
2021 Anti-NKG2C/IL-15/anti-CD33 killer engager directs primary and iPSC-derived NKG2C+ NK cells to target myeloid leukemia. Molecular therapy : the journal of the American Society of Gene Therapy 42 34174441
2016 Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans. Clinical and experimental immunology 41 26940026
2012 Assessment of copy-number variation in the NKG2C receptor gene in a single-tube and characterization of a reference cell panel, using standard polymerase chain reaction. Tissue antigens 41 22708664
2018 Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections. Frontiers in immunology 40 29731749
2016 NKG2C(+)CD57(+) Natural Killer Cell Expansion Parallels Cytomegalovirus-Specific CD8(+) T Cell Evolution towards Senescence. Journal of immunology research 40 27314055
2018 Tracking KLRC2 (NKG2C)+ memory-like NK cells in SIV+ and rhCMV+ rhesus macaques. PLoS pathogens 38 29851983
2019 NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients. Transplantation 37 30211828
2010 NKG2A inhibits NKG2C effector functions of γδ T cells: implications in health and disease. Journal of leukocyte biology 36 20952657
2005 Molecular and functional characterization of NKG2D, NKp80, and NKG2C triggering NK cell receptors in rhesus and cynomolgus macaques: monitoring of NK cell function during simian HIV infection. Journal of immunology (Baltimore, Md. : 1950) 36 15843571
2013 Expansion of the NKG2C+ natural killer-cell subset is associated with high-risk carotid atherosclerotic plaques in seropositive patients for human cytomegalovirus. Arteriosclerosis, thrombosis, and vascular biology 35 23968979
2016 The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease. International journal of molecular sciences 31 27801784
2022 Identification of a distinct NK-like hepatic T-cell population activated by NKG2C in a TCR-independent manner. Journal of hepatology 30 35644434
2013 Deletion of the activating NKG2C receptor and a functional polymorphism in its ligand HLA-E in psoriasis susceptibility. Experimental dermatology 30 24079744
2006 Evidence of NK cell dysfunction in SIV-infected rhesus monkeys: impairment of cytokine secretion and NKG2C/C2 expression. European journal of immunology 30 16906533
2018 NKG2C Deletion Is a Risk Factor for Human Cytomegalovirus Viremia and Disease After Lung Transplantation. The Journal of infectious diseases 28 29220498
1995 NKG2-C is a receptor on human natural killer cells that recognizes structures on K562 target cells. European journal of immunology 28 7589093
2023 Activating NKG2C Receptor: Functional Characteristics and Current Strategies in Clinical Applications. Archivum immunologiae et therapiae experimentalis 26 36899273
2012 NMR observable-based structure refinement of DAP12-NKG2C activating immunoreceptor complex in explicit membranes. Biophysical journal 25 22500771
2007 Association of CD94/NKG2A, CD94/NKG2C, and its ligand HLA-E polymorphisms with Behcet's disease. Tissue antigens 25 17767552
2024 NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control. JCI insight 24 39288262
2008 Inhibitory NKG2A and activating NKG2D and NKG2C natural killer cell receptor genes: susceptibility for rheumatoid arthritis. Tissue antigens 24 18700876
2006 NKG2C+ NK cells are enriched in AIDS patients with advanced-stage Kaposi's sarcoma. Journal of virology 24 17035308
2020 Responsiveness to Influenza Vaccination Correlates with NKG2C-Expression on NK Cells. Vaccines 23 32517137
2019 Pretransplant adaptive NKG2C+ NK cells protect against cytomegalovirus infection in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 23 31612635
2015 Upregulation of NKG2C+ natural killer cells, TLR-2 expression on monocytes and downregulation of regulatory T-cells influence PEG-IFN treatment efficacy in entecavir-suppressed patients with CHB. Antiviral therapy 23 25814467
2022 NKG2C+ NK Cells for Immunotherapy of Glioblastoma Multiforme. International journal of molecular sciences 22 35628668
2020 CD56dim CD57- NKG2C+ NK cells retaining proliferative potential are possible precursors of CD57+ NKG2C+ memory-like NK cells. Journal of leukocyte biology 22 32930385
2019 Phenotypic and Functional Analysis of Human NK Cell Subpopulations According to the Expression of FcεRIγ and NKG2C. Frontiers in immunology 22 31867015
2012 Functional profile of cytomegalovirus (CMV)-specific CD8+ T cells and kinetics of NKG2C+ NK cells associated with the resolution of CMV DNAemia in allogeneic stem cell transplant recipients. Journal of medical virology 22 22170546
2017 Elusive Role of the CD94/NKG2C NK Cell Receptor in the Response to Cytomegalovirus: Novel Experimental Observations in a Reporter Cell System. Frontiers in immunology 21 29114247
2015 Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+ population. Lancet (London, England) 21 26312867
2015 Polyclonal Expansion of NKG2C(+) NK Cells in TAP-Deficient Patients. Frontiers in immunology 21 26500647
2013 Expansion of CMV-mediated NKG2C+ NK cells associates with the development of specific de novo malignancies in liver-transplanted patients. Journal of immunology (Baltimore, Md. : 1950) 21 24307732
2021 HCMV-controlling NKG2C+ NK cells originate from novel circulating inflammatory precursors. The Journal of allergy and clinical immunology 20 33493558
2016 Human Adaptive Natural Killer Cells: Beyond NKG2C. Trends in immunology 20 27179621
2009 Women with pre-eclampsia have an altered NKG2A and NKG2C receptor expression on peripheral blood natural killer cells. American journal of reproductive immunology (New York, N.Y. : 1989) 20 19694640
2016 Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C+ Natural Killer Cells. Journal of innate immunity 19 27116381
2014 Distinct natural killer cells in HIV-exposed seronegative subjects with effector cytotoxic CD56(dim) and CD56(bright) cells and memory-like CD57⁺NKG2C⁺CD56(dim) cells. Journal of acquired immune deficiency syndromes (1999) 19 25230289
2022 Deletion of the Natural Killer Cell Receptor NKG2C Encoding KLR2C Gene and Kidney Transplant Outcome. Frontiers in immunology 18 35401541
2022 Donor NKG2C homozygosity contributes to CMV clearance after haploidentical transplantation. JCI insight 16 34990406
2018 Donor NKG2C Copy Number: An Independent Predictor for CMV Reactivation After Double Cord Blood Transplantation. Frontiers in immunology 16 30405633
2016 Differential frequency of NKG2C/KLRC2 deletion in distinct African populations and susceptibility to Trachoma: a new method for imputation of KLRC2 genotypes from SNP genotyping data. Human genetics 16 27312142
2015 Functional anti-CD94/NKG2A and anti-CD94/NKG2C autoantibodies in patients with systemic lupus erythematosus. Arthritis & rheumatology (Hoboken, N.J.) 16 25510434
2012 Short communication: NKG2C+ NK cells contribute to increases in CD16+CD56- cells in HIV type 1+ individuals with high plasma viral load. AIDS research and human retroviruses 16 22920222
2023 Inhibitory NKG2A+ and absent activating NKG2C+ NK cell responses are associated with the development of EBV+ lymphomas. Frontiers in immunology 15 37426645
2013 NKG2C gene deletion in the Mexican population and lack of association to respiratory viral infections. International journal of immunogenetics 15 24305414
2009 The CD94/NKG2C-expressing NK cell subset is augmented in chronic lymphocytic leukemia patients with positive human cytomegalovirus serostatus. Viral immunology 15 19811091
2013 NKG2C, HLA-E and their association with psoriasis. Experimental dermatology 14 24279916
2020 Adaptive NKG2C+ natural killer cells are related to exacerbations and nutritional abnormalities in COPD patients. Respiratory research 13 32131843
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
2021 Influence of NKG2C Genotypes on HIV Susceptibility and Viral Load Set Point. Journal of virology 12 34076484
2019 Enrichment of Cytomegalovirus-induced NKG2C+ Natural Killer Cells in the Lung Allograft. Transplantation 12 30461721
2018 Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis. RMD open 12 30018803
1997 The CD94/NKG2 C-type lectin receptor complex: involvement in NK cell-mediated recognition of HLA class I molecules. Immunologic research 12 9212363

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