Affinage

KLRC2

NKG2-C type II integral membrane protein · UniProt P26717

Length
231 aa
Mass
26.2 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLRC2 (NKG2C) encodes an activating C-type lectin-like receptor that heterodimerizes covalently with CD94 and associates non-covalently with the ITAM-bearing adaptor DAP12 through complementary charged transmembrane residues (Lys in NKG2C, Asp/Thr in DAP12), forming a trimolecular signaling complex on NK cells, γδ T cells, and subsets of CD8+ T cells (PMID:9655483, PMID:22500771, PMID:20952657). The CD94/NKG2C complex recognizes HLA-E in a peptide-dependent manner with lower affinity and faster kinetics than the inhibitory CD94/NKG2A, engaging a largely overlapping but partly distinct set of HLA-E contact residues; upon ligation it signals through DAP12-dependent MAPK/ERK activation and calcium mobilization to trigger cytotoxicity, cytokine production (TNF-α, IFN-γ), and proliferation (PMID:10428963, PMID:14971033, PMID:11069065, PMID:9103421). KLRC2 gene copy number quantitatively controls receptor surface density, calcium signaling magnitude, and degranulation capacity, and HCMV-driven expansion of NKG2C+ adaptive NK cells requires both monocyte-derived IL-12 and the NKG2C/HLA-E axis, with CD2 serving as an alternative co-stimulatory pathway when NKG2C is absent (PMID:24030638, PMID:25384219, PMID:27117418). The KLRC2 locus undergoes homozygous deletion in approximately 4% of humans, yet NKG2C-deficient individuals can still generate adaptive NK cells with epigenetically reprogrammed IFN-γ loci, indicating functional redundancy in the adaptive NK cell differentiation program (PMID:14688071, PMID:27117418).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1995 Medium

    Initial identification of NKG2C as an NK cell surface glycoprotein whose soluble form binds NK target cells established it as a candidate recognition receptor, though its ligand and signaling mode were unknown.

    Evidence Recombinant soluble NKG2C binding assay on K562/RPMI 8866 target cells with differentiation controls

    PMID:7589093

    Open questions at the time
    • Ligand identity on target cells not determined
    • Activating versus inhibitory function not resolved
    • Single-lab observation without independent replication
  2. 1997 High

    Chimeric receptor experiments resolved the key question of whether NKG2C delivers activating or inhibitory signals, demonstrating that NKG2C triggers cytotoxicity and calcium mobilization without recruiting the inhibitory phosphatase SHP-1.

    Evidence NKG2C/NKR-P1C chimeric receptors in RNK-16 cells; cytolytic assays, calcium flux, SHP-1 co-IP

    PMID:9103421

    Open questions at the time
    • Signaling adaptor mediating activation not yet identified
    • Physiological ligand still unknown
  3. 1998 High

    Two contemporaneous studies established the molecular architecture of the activating receptor complex: NKG2C covalently heterodimerizes with CD94 and non-covalently recruits the ITAM-bearing adaptor DAP12 via charge-complementary transmembrane residues, explaining how a receptor lacking intrinsic signaling motifs triggers activation.

    Evidence Co-IP, transmembrane mutagenesis, COS7 co-transfection, redirected killing assays

    PMID:9485212 PMID:9655483

    Open questions at the time
    • Stoichiometry and structural details of the DAP12–NKG2C transmembrane assembly not resolved
    • Downstream signaling cascade not mapped
  4. 1999 High

    Identification of HLA-E as the ligand for CD94/NKG2C—and demonstration that NKG2C binds HLA-E with lower affinity and faster kinetics than inhibitory NKG2A—answered how activation and inhibition are balanced through a shared ligand with differential binding strength.

    Evidence Surface plasmon resonance with recombinant soluble CD94/NKG2C and peptide-loaded HLA-E; mouse Qa-1b binding with blocking mAb

    PMID:10428963 PMID:10601355

    Open questions at the time
    • Structural basis for affinity difference between NKG2C and NKG2A not determined
    • Peptide selectivity of NKG2C recognition not fully characterized
  5. 2000 High

    Reconstitution of the complete CD94/NKG2C/DAP12 complex in heterologous cells mapped the downstream signaling cascade to MAPK/ERK, showing that MEK inhibition blocks TNF-α production and cytotoxicity—establishing the first defined intracellular pathway downstream of NKG2C engagement.

    Evidence RBL cell transfection with CD94/NKG2C/DAP12; MAPK phosphorylation, calcium flux, serotonin release; MEK inhibitor PD098059

    PMID:11069065

    Open questions at the time
    • Role of other signaling branches (PI3K, NF-κB) not addressed
    • In vivo signaling relevance not tested
  6. 2004 High

    Alanine-scanning mutagenesis of HLA-E resolved how CD94/NKG2C and CD94/NKG2A discriminate the same ligand: they share most contact residues on the HLA-E α1/α2 platform, but two residues (D69, H155) are selectively required for NKG2A but not NKG2C binding, providing a structural explanation for differential affinity.

    Evidence Systematic alanine mutagenesis of HLA-E surface residues; binding analysis with soluble CD94/NKG2A and CD94/NKG2C

    PMID:14971033

    Open questions at the time
    • No crystal structure of CD94/NKG2C–HLA-E complex available
    • Energetic contribution of each contact not quantified
  7. 2004 High

    Discovery that KLRC2 undergoes complete homozygous deletion in ~4% of humans (allele frequency ~20%) revealed that the gene is dispensable for survival and created a natural human knockout model for studying NKG2C function.

    Evidence PCR genotyping and breakpoint mapping in deletion versus wild-type haplotypes

    PMID:14688071

    Open questions at the time
    • Functional consequences of deletion for immune defense not yet assessed
    • Selective pressure maintaining or driving deletion frequency unknown
  8. 2005 High

    Extension of NKG2C function beyond NK cells: demonstration that CD94/NKG2C coupled to DAP12 on CD8+ T cells triggers cytotoxicity, cytokine release, and proliferation established NKG2C as an alternative activation pathway for adaptive lymphocytes.

    Evidence Co-IP of DAP12 via anti-CD94 in T cell clones; cytotoxicity, cytokine, and proliferation assays

    PMID:15940674

    Open questions at the time
    • Proportion and phenotype of NKG2C+ T cells in different tissues not systematically characterized
    • TCR-independent versus TCR-dependent triggering not dissected
  9. 2009 High

    Discovery of a negative feedback loop: IL-12 transiently induces inhibitory NKG2A on NKG2C+ NK cells, dampening their HLA-E-mediated activation—establishing that NKG2A/NKG2C balance is dynamically regulated by cytokine milieu.

    Evidence IL-12 stimulation and anti-IL-12 blockade in co-culture with HCMV-infected DCs; anti-NKG2A functional inhibition

    PMID:19124726

    Open questions at the time
    • Transcriptional mechanism of IL-12-driven NKG2A induction on NKG2C+ cells not identified
    • Duration and reversibility of NKG2A co-expression in vivo unknown
  10. 2012 Medium

    NMR-restrained MD simulations revealed the atomic-level arrangement of the DAP12–NKG2C transmembrane assembly: a salt-bridge/hydrogen-bond network involving two Asp and two Thr in the DAP12 dimer and one Lys in NKG2C stabilizes the complex within the membrane.

    Evidence NMR observable-based MD simulation in explicit micelles and lipid bilayers

    PMID:22500771

    Open questions at the time
    • No independent mutagenesis validation of predicted contacts reported in this study
    • Structure of the full ectodomain–transmembrane complex not resolved
    • Computational model in micelles may not fully reflect native bilayer environment
  11. 2013 High

    Gene dosage quantitatively controls NKG2C function: KLRC2 copy number determines receptor surface density, calcium signaling amplitude, degranulation efficiency, and IL-15-dependent proliferation, providing a mechanistic basis for population-level variation in NKG2C-dependent immune responses.

    Evidence Flow cytometry, calcium mobilization, CD107a degranulation, and proliferation assays stratified by NKG2C genotype across multiple donors

    PMID:24030638

    Open questions at the time
    • Whether gene dose effects extend to in vivo viral control not tested
    • Epigenetic regulation of KLRC2 expression beyond copy number not explored
  12. 2014 High

    HCMV-driven expansion of adaptive NKG2C+ NK cells was shown to require dual signals: monocyte-derived IL-12 and direct NKG2C/HLA-E engagement, with each independently necessary—resolving a long-standing question about the signals driving adaptive NK cell generation.

    Evidence Co-culture with HCMV-infected fibroblasts and monocytes; IL-12 neutralization, NKG2C blocking mAb, HLA-E siRNA silencing

    PMID:25384219

    Open questions at the time
    • Role of other cytokines (IL-18, IL-15) as co-factors not fully dissected in this system
    • Molecular mechanism linking HLA-E engagement to clonal expansion not identified
  13. 2016 High

    Analysis of NKG2C-null humans revealed functional redundancy in adaptive NK cell differentiation: NKG2C−/− individuals generate adaptive NK cells with characteristic epigenetic and phenotypic features, using CD2 as an alternative co-stimulatory receptor that synergistically enhances ERK/S6RP signaling after CD16 ligation.

    Evidence Repertoire analysis in 60 NKG2C−/− donors; phospho-flow for ERK/S6RP; CD2 blocking; ADCC assay; IFN-γ promoter methylation analysis

    PMID:27117418

    Open questions at the time
    • Whether CD2-dependent adaptive NK cells are functionally equivalent to NKG2C+ cells in viral control unknown
    • Epigenetic mechanisms driving compensatory pathway engagement not defined
  14. 2017 Medium

    Viral strain specificity of NKG2C activation was established: clinical HCMV isolates and endotheliotropic TB40/E, but not laboratory strains AD169/Towne, activate CD94/NKG2C/DAP12-dependent NFAT/AP1 reporter signaling, suggesting that specific viral gene products or altered HLA-E peptide repertoires determine receptor engagement.

    Evidence Jurkat reporter cells expressing CD94/NKG2C/DAP12 with NFAT/AP1-luciferase; antibody blocking; co-culture with HCMV-infected cells

    PMID:29114247

    Open questions at the time
    • Specific viral gene or peptide responsible for strain-dependent activation not identified
    • Reporter cell system may not fully recapitulate primary NK cell signaling thresholds
  15. 2019 Medium

    NKG2C+ adaptive NK cells were shown to constitutively express HLA-DR and function as unconventional antigen-presenting cells, loading HCMV antigens via CD16 and presenting them to effector-memory CD4+ T cells—revealing an unanticipated bridge between innate and adaptive immunity.

    Evidence HLA-DR blocking antibody; co-culture of HCMV-antigen-loaded NK cells with autologous CD4+ T cells; intracellular cytokine staining

    PMID:31001281

    Open questions at the time
    • Mechanism of antigen processing and HLA-DR loading in NK cells not characterized
    • In vivo relevance of NK cell antigen presentation not established
    • Single-lab finding without independent replication
  16. 2022 Medium

    Identification of a liver-resident CD56hiCD161−CD8+ T cell population highly expressing NKG2C demonstrated tissue-specific innate-like T cell function driven by NKG2C ligation independently of TCR, expanding the functional scope of NKG2C to hepatic immunity.

    Evidence CITE-seq with TCR-seq, flow cytometry, TCR-independent NKG2C functional assays on intrahepatic cells

    PMID:35644434

    Open questions at the time
    • Ligand (HLA-E or other) driving NKG2C activation in liver sinusoidal environment not confirmed
    • Contribution of this subset to liver disease or viral hepatitis defense unknown
    • Single-cohort observation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the crystal structure of the CD94/NKG2C–HLA-E ternary complex, the specific HCMV-derived peptides or viral factors responsible for strain-dependent NKG2C activation, the transcriptional and epigenetic regulation of KLRC2 during adaptive NK cell differentiation, and the in vivo contribution of NKG2C signaling to HCMV control versus the compensatory CD2-dependent pathway.
  • No crystal structure of CD94/NKG2C–HLA-E complex
  • Viral determinants of strain-specific NKG2C activation unidentified
  • In vivo functional equivalence of NKG2C-dependent versus CD2-dependent adaptive NK pathways untested

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
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 3
Partners
CD2CD94DAP12HLA-E
Complex memberships
CD94/NKG2CCD94/NKG2C/DAP12

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 NKG2C delivers an activating signal in NK cells: chimeric receptor constructs (NKG2C/NKR-P1C) stimulated lytic activity and calcium mobilization in RNK-16 cells, while SHP-1 did not associate with the NKG2C cytoplasmic domain (unlike the inhibitory NKG2A), establishing NKG2C as an activating receptor. Chimeric receptor transfection in rat NK cell line, cytolytic assay, calcium mobilization, immunoprecipitation Journal of immunology High 9103421
1998 CD94/NKG2C forms a non-covalent complex with DAP12 (an ITAM-bearing adaptor), and charged residues in the transmembrane domains of both DAP12 and NKG2C are required for this interaction and for efficient surface expression of the receptor. Co-immunoprecipitation, surface expression analysis, transmembrane domain mutagenesis Immunity High 9655483
1998 NKG2C (Kp39) covalently associates with CD94 to form an activating receptor complex on a subset of NKG2A-negative NK cells; cytolytic activity of NKG2A−P25+ NK clones can be triggered by an NKG2C-specific mAb in redirected killing, and biochemical analysis of COS7 cells co-transfected with CD94 and NKG2C confirmed the identity of Kp39 as NKG2C. Immunoprecipitation, peptide mapping, RT-PCR, COS7 co-transfection, redirected killing assay European journal of immunology High 9485212
1999 CD94/NKG2C binds HLA-E in a peptide-dependent manner; the activating CD94/NKG2C receptor has a lower binding affinity for HLA-E than the inhibitory CD94/NKG2A receptor, with very fast association and dissociation kinetics, and the affinity of peptide-HLA-E complexes correlates with NK cell response. Surface plasmon resonance (kinetic binding analysis) with soluble recombinant HLA-E and soluble CD94/NKG2C proteins, peptide-dependent assembly The EMBO journal High 10428963
1999 Mouse CD94/NKG2C (and CD94/NKG2E) bind to the non-classical MHC class Ib molecule Qa-1b, the mouse functional counterpart of HLA-E, and these receptors likely function as activating receptors based on cytoplasmic domain features distinct from inhibitory NKG2A; CD94/NKG2 molecules are the only Qa-1b receptors on NK cells. Cloning and expression, novel blocking anti-NKG2 mAb, binding assay, molecular analysis of cytoplasmic domains The Journal of experimental medicine High 10601355
2000 Engagement of CD94/NKG2C on NK cells activates the MAPK (ERK) pathway; MEK inhibitor PD098059 reduces CD94/NKG2C-dependent TNF-α production and cytotoxicity; transfer of CD94/NKG2C/DAP12 into RBL cells reconstitutes calcium mobilization, serotonin release, and MAPK phosphorylation upon receptor cross-linking. MEK inhibitor pharmacological blockade, MAPK phosphorylation assay, RBL cell transfection with CD94/NKG2C/DAP12, calcium mobilization, serotonin release assay European journal of immunology High 11069065
2004 CD94/NKG2C and CD94/NKG2A bind the top of HLA-E (α1/α2 domain) through mostly shared but partly distinct sets of HLA-E residues; two HLA-E mutations (D69A and H155A) selectively abrogate binding to CD94/NKG2A but not CD94/NKG2C, revealing differential contact residues for the activating versus inhibitory receptor. Alanine-scanning mutagenesis of HLA-E, binding analysis with soluble CD94/NKG2A and CD94/NKG2C European journal of immunology High 14971033
2004 The KLRC2 (NKG2C) gene is subject to complete homozygous deletion in ~4% of humans (deletion allele frequency ~20%), established by molecular genetic analysis identifying the deletion breakpoint 1.5–1.8 kb telomeric from the 3′ end of NKG2A. PCR genotyping, sequence comparison of intergenic regions in deletion versus wild-type haplotypes International immunology High 14688071
2005 CD94/NKG2C is expressed on a CD8+ T cell subset, is coupled to DAP12/KARAP (co-precipitated by anti-CD94 mAb), and its engagement triggers cytotoxicity, cytokine production, IL-2Rα upregulation, and proliferation in CD94/NKG2C+ T cell clones, establishing it as a functional alternative T cell activation pathway. Co-immunoprecipitation (anti-CD94 pulldown of DAP12), cytotoxicity assay, cytokine production assay, proliferation assay, flow cytometry European journal of immunology High 15940674
2009 IL-12 transiently induces surface NKG2A expression on CD94/NKG2C+ NK cells (including upon co-culture with HCMV-infected dendritic cells, blocked by anti-IL-12 mAb), and this de novo NKG2A inhibits the cytolytic activity of NKG2C+ NK clones upon HLA-E engagement, revealing a negative regulatory feedback mechanism. In vitro stimulation with irradiated PBMC or rIL-12, anti-IL-12 mAb blockade, anti-NKG2A mAb functional inhibition assay, flow cytometry Journal of immunology High 19124726
2012 NMR-based structural study of the DAP12-NKG2C transmembrane helix complex in explicit membranes revealed 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; MD simulations refined side-chain arrangements consistent with available experimental constraints. NMR observable-based MD simulation in explicit micelles and bilayers, distance restraints Biophysical journal Medium 22500771
2013 NKG2C zygosity (gene copy number) quantitatively influences CD94/NKG2C surface receptor levels, calcium influx signaling, degranulation, and IL-15-dependent proliferation upon receptor engagement, establishing a mechanistic link between KLRC2 copy number and receptor functional output in NK cells. Flow cytometry (surface levels, degranulation CD107a), intracellular calcium mobilization assay, proliferation assay, NKG2C genotyping in cohort European journal of immunology High 24030638
2014 Expansion of NKG2C+ NK cells in response to HCMV requires both IL-12 from CD14+ inflammatory monocytes and the CD94/NKG2C/HLA-E axis: IL-12 neutralization substantially reduced NKG2C+ subset expansion and CD25 upregulation, while NKG2C blockade or HLA-E silencing in infected fibroblasts greatly impaired expansion. Co-culture system with HCMV-infected fibroblasts and monocytes, IL-12 neutralizing antibody, NKG2C-blocking mAb, HLA-E siRNA silencing, flow cytometry The Journal of clinical investigation High 25384219
2015 HLA-E regulates NKG2C+ NK cell degranulation (CD107a) in a peptide-restricted manner: only 4 specific peptides (CMV-I, A80, B13, and HLA-G-derived) enhance NKG2C-mediated activation, and the HLA-E:G peptide complex triggers NKG2C receptor internalization reversible by bafilomycin. Degranulation assay (CD107a), flow cytometry, peptide-pulsed HLA-E target cells, bafilomycin treatment Human immunology Medium 26382247
2016 NKG2C-deficient (NKG2C−/−) humans still generate adaptive NK cells with characteristic footprints (terminally differentiated phenotype, epigenetic IFN-γ promoter remodeling, functional reprogramming); these adaptive NK cells express high CD2, which synergistically enhances ERK and S6RP phosphorylation after CD16 ligation and is critical for antibody-coated target cell responses. NK cell repertoire analysis in 60 NKG2C−/− donors, phospho-flow (ERK, S6RP), CD2 blocking/stimulation, ADCC assay, epigenetic methylation analysis Cell reports High 27117418
2017 Activation of CD94/NKG2C by ligands displayed on HCMV-infected cells is dependent on viral strain: clinical isolates and endotheliotropic TB40/E strain (but not laboratory strains AD169/Towne) activate Jurkat-NKG2C+ reporter cells, and HLA-E+ 721.221 cells trigger NKG2C/DAP12-dependent NFAT/AP1 reporter activity antagonized by anti-NKG2C and anti-HLA-E mAbs. Jurkat reporter cell line expressing CD94/NKG2C/DAP12 with NFAT/AP1-luciferase reporter, antibody blocking, co-culture with HCMV-infected cells Frontiers in immunology Medium 29114247
2019 NKG2C+ adaptive NK cells constitutively express HLA-DR and, after HCMV antigen loading via CD16 (accompanied by CD16 loss and CX3CR1 decrease), present HCMV antigens in an HLA-DR-dependent manner to CD28-negative effector-memory CD4+ T cells, inducing degranulation (CD107a) and Th1 cytokines (IFN-γ, TNF-α). Flow cytometry, HLA-DR blocking antibody, co-culture of HCMV-antigen-loaded NK cells with autologous CD4+ T cells, intracellular cytokine staining Frontiers in immunology Medium 31001281
1995 NKG2C is expressed as a 36-kDa glycoprotein on NK cells; a soluble recombinant NKG2C protein binds specifically to K562 and RPMI 8866 cells (NK targets/feeders) but not to other hematopoietic lines, and binding structures disappear concomitant with loss of K562 susceptibility to killing upon differentiation induction. In vitro translation, recombinant protein expression, immunoprecipitation, soluble receptor binding assay, target cell differentiation European journal of immunology Medium 7589093
2010 In γδ T cells, CD94/NKG2C associated with KARAP/DAP12 is fully functional (mediates 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. IFN-γ ELISA, proliferation assay, cytolytic activity assay, functional co-expression experiments with NKG2A/NKG2C double-positive cells Journal of leukocyte biology Medium 20952657
2022 A distinct CD56hiCD161-CD8+ T-cell population in human liver sinusoids highly expresses NKG2C and exerts NKG2C-mediated NK-like effector functions (cytotoxicity, cytokine production) in the absence of TCR stimulation, activated by innate cytokines (IL-12/18, IL-15). CITE-seq with TCR-seq, flow cytometry, functional assays (TCR-independent NKG2C ligation), intrahepatic cell isolation Journal of hepatology Medium 35644434

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 429 9655483
2005 Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood 355 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) 306 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 298 10428963
2011 CMV drives clonal expansion of NKG2C+ NK cells expressing self-specific KIRs in chronic hepatitis patients. European journal of immunology 240 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 190 27117418
1997 Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. Journal of immunology (Baltimore, Md. : 1950) 186 9103421
2015 CD56dimCD57+NKG2C+ NK cell expansion is associated with reduced leukemia relapse after reduced intensity HCT. Leukemia 185 26416461
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
2014 IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. The Journal of clinical investigation 158 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) 149 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) 144 24442432
2010 Chronic HIV-1 viremia reverses NKG2A/NKG2C ratio on natural killer cells in patients with human cytomegalovirus co-infection. AIDS (London, England) 122 19910789
2023 Single-cell atlas of healthy human blood unveils age-related loss of NKG2C+GZMB-CD8+ memory T cells and accumulation of type 2 memory T cells. Immunity 121 37963457
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 104 33500568
2014 The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection. Seminars in immunology 93 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 74 24030638
2013 Cytotoxic NKG2C+ CD4 T cells target oligodendrocytes in multiple sclerosis. Journal of immunology (Baltimore, Md. : 1950) 73 23396942
2005 The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells. European journal of immunology 73 15940674
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 66 14688071
2016 Relationship of NKG2C Copy Number with the Distribution of Distinct Cytomegalovirus-Induced Adaptive NK Cell Subsets. Journal of immunology (Baltimore, Md. : 1950) 63 26994220
2009 IL-12-dependent inducible expression of the CD94/NKG2A inhibitory receptor regulates CD94/NKG2C+ NK cell function. Journal of immunology (Baltimore, Md. : 1950) 63 19124726
2012 NKG2C deletion is a risk factor of HIV infection. AIDS research and human retroviruses 61 22074011
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
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) 56 18097224
2016 Adaptive NKG2C+ NK Cell Response and the Risk of Cytomegalovirus Infection in Kidney Transplant Recipients. Journal of immunology (Baltimore, Md. : 1950) 55 27913630
2016 NKG2C/E Marks the Unique Cytotoxic CD4 T Cell Subset, ThCTL, Generated by Influenza Infection. Journal of immunology (Baltimore, Md. : 1950) 55 28031335
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 54 16488482
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 HLA-E regulates NKG2C+ natural killer cell function through presentation of a restricted peptide repertoire. Human immunology 53 26382247
2015 Activating KIRs and NKG2C in Viral Infections: Toward NK Cell Memory? Frontiers in immunology 52 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 48 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 46 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 43 31001281
2012 Spotlight on NKG2C and the human NK-cell response to CMV infection. European journal of immunology 42 23255011
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
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 39 34174441
2018 Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections. Frontiers in immunology 39 29731749
2016 NKG2C(+)CD57(+) Natural Killer Cell Expansion Parallels Cytomegalovirus-Specific CD8(+) T Cell Evolution towards Senescence. Journal of immunology research 39 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 36 30211828
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