Affinage

KLRC1

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

Length
233 aa
Mass
26.3 kDa
Annotated
2026-04-28
88 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KLRC1 encodes NKG2A, a type II transmembrane C-type lectin-domain protein that forms a disulfide-linked inhibitory heterodimer with CD94 on NK cells, CD8+ T cells, γδ T cells, and iNKT cells, serving as a central checkpoint receptor that monitors HLA class I expression through recognition of HLA-E loaded with signal-sequence-derived nonapeptides (PMID:2007850, PMID:8943374, PMID:9480992). Ligand engagement induces tyrosine phosphorylation of the NKG2A ITIM motifs and recruitment of the SHP-1 phosphatase, which blocks proximal signaling through Syk, ERK, and Shc/Grb-2, thereby suppressing cytotoxicity and cytokine production (PMID:9103421, PMID:9565368, PMID:10358164). The CD94/NKG2A heterodimer binds HLA-E with higher affinity than its activating counterpart CD94/NKG2C, with peptide conformation within the HLA-E groove—rather than heavy-chain differences—determining differential receptor engagement, and CD94 contributing the dominant ligand-contact surface as revealed by crystal structures (PMID:10428963, PMID:18083576, PMID:18339401). Beyond canonical immune surveillance, this receptor axis operates in decidual NK cell tolerance to trophoblast HLA-E, in LAG-3-dependent exhausted CD8+ T cell subsets during chronic viral infection, and in microglial regulation of ocular dominance plasticity (PMID:10898498, PMID:39121847, PMID:35648829).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1991 High

    Molecular cloning established that KLRC1 encodes a novel NK-cell-expressed type II membrane protein with a C-type lectin domain, revealing the gene's identity and basic structural architecture.

    Evidence cDNA library screening and full-length sequencing from an NK cell line

    PMID:2007850

    Open questions at the time
    • Ligand unknown
    • Signaling function unknown
    • Heterodimeric partner not yet identified
  2. 1996 High

    Biochemical studies revealed that NKG2A obligately heterodimerizes with CD94 via disulfide bonds and that its cytoplasmic ITIMs provide the structural basis for inhibitory signaling, resolving how the receptor complex assembles and predicting its inhibitory function.

    Evidence Reciprocal co-immunoprecipitation and ITIM motif identification across multiple labs

    PMID:8943374 PMID:9045931

    Open questions at the time
    • Ligand identity still unknown
    • ITIM-dependent phosphatase recruitment not yet demonstrated
  3. 1997 High

    Chimeric receptor assays and functional studies identified SHP-1 phosphatase recruitment to phosphorylated NKG2A as the proximal mechanism of inhibition, and demonstrated that HLA-E (loaded with HLA class I signal peptides) is the ligand—with CD94/NKG2A also mediating inhibition of decidual NK killing of HLA-G-expressing trophoblast via HLA-E.

    Evidence Chimeric receptor transfection with SHP-1 co-IP; NK cytotoxicity assays with synthetic peptides and anti-CD94 blocking; decidual NK clone assays

    PMID:9103421 PMID:9190923 PMID:9233599 PMID:9480992

    Open questions at the time
    • Quantitative binding affinity not measured
    • Structural basis of HLA-E recognition unknown
    • Downstream signaling cascade beyond SHP-1 not mapped
  4. 1998 High

    Ligand engagement was shown to induce NKG2A tyrosine phosphorylation and SHP-1 recruitment in intact cells, confirming the ITIM→SHP-1 model; peptide selectivity studies revealed that peptide conformation within HLA-E governs differential recognition by inhibitory NKG2A versus activating NKG2C.

    Evidence Cross-linking, phosphorylation assays, heterologous RBL transfectants; NK clones with systematic peptide panels

    PMID:9565368 PMID:9754572

    Open questions at the time
    • Binding kinetics not quantified
    • No structural explanation for peptide discrimination
  5. 1999 High

    Biophysical measurements established that CD94/NKG2A binds HLA-E with higher affinity than CD94/NKG2C, explaining how the inhibitory receptor dominates under physiological conditions; signaling studies mapped the downstream inhibitory cascade to blockade of Syk, ERK, and Shc/Grb-2 pathways.

    Evidence Surface plasmon resonance with recombinant proteins; antibody co-crosslinking with Western blot for Syk, ERK, Shc phosphorylation

    PMID:10023772 PMID:10358164 PMID:10428963

    Open questions at the time
    • No co-crystal of CD94/NKG2A with HLA-E
    • Structural basis for affinity difference between NKG2A and NKG2C unclear
  6. 2000 High

    CD94/NKG2A was shown to cross-inhibit activating receptors including CD69-triggered ERK signaling, and HLA-E tetramer binding confirmed the pathway operates in decidual NK cells to maintain fetal tolerance.

    Evidence RBL transfectants co-expressing CD69 and CD94/NKG2A with ERK and degranulation assays; HLA-E tetramer staining of decidual NK cells

    PMID:10671222 PMID:10898498

    Open questions at the time
    • Relative contribution of CD94/NKG2A versus KIR to maternal-fetal tolerance not resolved
    • In vivo relevance in human pregnancy not tested
  7. 2004 Medium

    Transmembrane domain determinants were found to explain preferential surface expression of NKG2A over NKG2C in the absence of DAP12, providing a mechanism for default inhibitory bias at the cell surface.

    Evidence Transfection of NKG2A/NKG2C chimeras into COS cells ± DAP12, flow cytometry

    PMID:15153509

    Open questions at the time
    • Study used rhesus monkey sequences; human equivalence assumed but not directly tested
    • Quantitative stoichiometry on primary human NK cells not determined
  8. 2007 High

    The crystal structure of the CD94–NKG2A heterodimer revealed an asymmetric interface and mutagenesis identified CD94 as the dominant HLA-E-contacting subunit, answering how the two chains divide labor in ligand recognition.

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

    PMID:18083576

    Open questions at the time
    • Full ternary complex structure (CD94/NKG2A bound to HLA-E/peptide) not yet solved at this point
    • How NKG2A ITIM accessibility changes upon ligand binding structurally unresolved
  9. 2008 High

    Comparative crystallography of HLA-E with different peptides showed that subtle peptide conformational changes—not HLA-E heavy chain rearrangements—govern differential CD94/NKG2 recognition, explaining peptide-dependent selectivity at atomic resolution.

    Evidence Dual crystal structures of HLA-E/peptide complexes at 2.5 Å

    PMID:18339401

    Open questions at the time
    • Ternary complex with receptor still not captured crystallographically
    • Dynamic aspects of peptide-dependent discrimination not addressed
  10. 2022 Medium

    The Qa-1/CD94/NKG2 axis was discovered to operate in microglia regulating neuronal ocular dominance plasticity, extending the receptor's functional role far beyond classical immune surveillance.

    Evidence Qa-1 knockout mice and pharmacological blockade of CD94/NKG2 in ocular dominance plasticity assays

    PMID:35648829

    Open questions at the time
    • Human relevance not established
    • Whether this involves NKG2A (inhibitory) or NKG2C (activating) signaling in microglia not distinguished
    • Downstream microglial effector mechanisms unknown
  11. 2023 High

    CRISPR knockout of KLRC1 in human NK cells eliminated HLA-E-mediated inhibition and enhanced anti-tumor cytotoxicity in vivo, validating NKG2A as a non-redundant immune checkpoint; concurrently, systematic analysis of HLA class I signal peptides showed only 6 of 16 variants efficiently engage CD94/NKG2A through HLA-E, revealing population-level heterogeneity in checkpoint strength.

    Evidence KLRC1 CRISPR KO NK cells in xenograft breast cancer model; quantitative peptide-HLA-E binding and receptor recognition assays across 16 signal peptide variants

    PMID:37264229 PMID:37675109

    Open questions at the time
    • Clinical translation of KLRC1 KO NK cell therapy not validated
    • How signal peptide competition shapes individual immune responses in vivo not fully modeled
  12. 2024 High

    LAG-3 was found to sustain a CD94/NKG2-expressing subset of exhausted CD8+ T cells with enhanced cytotoxicity via Qa-1b recognition, revealing a regulatory circuit that links T cell exhaustion programs to NKG2 receptor expression.

    Evidence LAG-3 KO in chronic LCMV infection model with single-cell profiling and Qa-1b blocking

    PMID:39121847

    Open questions at the time
    • Whether LAG-3 regulates NKG2A versus NKG2C specifically in this context not resolved
    • Human correlate of LAG-3/NKG2 axis in chronic infection or cancer not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full ternary crystal structure of CD94/NKG2A bound to HLA-E/peptide, the conformational dynamics linking ligand engagement to ITIM phosphorylation, how NKG2A versus NKG2C expression is regulated at the transcriptional level in different lymphocyte subsets, and whether the neuroimmune functions of this axis operate through canonical ITIM/SHP-1 signaling.
  • No ternary co-crystal structure of CD94/NKG2A/HLA-E/peptide published
  • Transcriptional regulation of KLRC1 in different cell lineages poorly defined
  • Mechanism of NKG2A function in microglia not molecularly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5
Partners
CD94DAP12HLA-ELAG-3NKG2CSHP-1
Complex memberships
CD94/NKG2A heterodimer

Evidence

Reading pass · 27 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 with a C-type lectin domain expressed on NK cells; NKG2-A and NKG2-B are alternative splicing products of a single gene (KLRC1). cDNA library screening, full-length cDNA sequencing, structural domain analysis The Journal of experimental medicine High 2007850
1996 NKG2A (KLRC1) forms disulfide-bonded heterodimers with CD94 on the NK cell surface; NKG2A/B possesses two immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its cytoplasmic domain, providing the molecular basis for inhibitory function. Co-immunoprecipitation, biochemical characterization, sequence analysis of ITIM motifs Journal of immunology High 8943374
1997 The CD94/NKG2-A inhibitory receptor complex (where NKG2-A is encoded by KLRC1) is formed by covalent association of CD94 with NKG2-A (~43 kDa); NKG2-B, the alternatively spliced product, also assembles with CD94. Both contain cytoplasmic ITIMs providing molecular basis for inhibitory function. Immunoprecipitation with anti-CD94 and NKG2-A-specific mAb (Z199), biochemical characterization European journal of immunology High 9045931
1997 NKG2-A (KLRC1) cytoplasmic domain delivers inhibitory signals to NK cells, while NKG2-C delivers activating signals; the inhibitory function of NKG2-A is mediated through selective recruitment of the tyrosine phosphatase SHP-1 to the NKG2-A/NKR-P1C chimeric receptor. Chimeric receptor transfection into RNK-16 NK cell line, cytolytic activity assay, calcium mobilization assay, immunoprecipitation of SHP-1 Journal of immunology High 9103421
1998 CD94/NKG2-A (KLRC1) specifically recognizes HLA-E complexed with peptides derived from HLA class I signal sequences; only peptides containing Met at position 2 (residue 4 of the signal sequence) confer resistance to NK-mediated lysis through CD94/NKG2-A recognition. NK cytotoxicity assays with synthetic peptides, antibody blocking with CD94-specific and KIR-specific mAbs, HLA-E surface upregulation assay The Journal of experimental medicine High 9480992
1998 Specific engagement of CD94/NKG2-A (KLRC1) by HLA-E or by anti-NKG2-A mAb induces tyrosine phosphorylation of the NKG2-A subunit and recruitment of SHP-1 phosphatase; this signaling cascade constitutes the molecular mechanism of CD94/NKG2-A-mediated inhibition. mAb cross-linking, Western blot for tyrosine phosphorylation, co-immunoprecipitation of SHP-1, transfection into RBL-2H3 cells, inhibition of Fc-epsilon-RI secretory events European journal of immunology High 9565368
1998 HLA-E-bound peptides influence recognition by inhibitory CD94/NKG2-A (KLRC1) and activating CD94/NKG2-C receptors; the HLA-G-derived nonamer peptide (VMAPRTLFL) engages the activating CD94/NKG2C receptor with significantly higher affinity than the inhibitory CD94/NKG2-A, triggering cytotoxicity. NK clone cytotoxicity assays with 721.221 cells loaded with synthetic leader sequence nonapeptides, HLA-E surface expression analysis European journal of immunology High 9754572
1999 CD94/NKG2-A (KLRC1) has higher binding affinity for HLA-E than the activating CD94/NKG2-C receptor; binding kinetics show very fast association and dissociation rate constants; recognition of HLA-E by both receptors is peptide-dependent with a direct correlation between binding affinity and NK cell response. Surface plasmon resonance (BIAcore) with soluble recombinant HLA-E and CD94/NKG2-A and CD94/NKG2-C proteins The EMBO journal High 10428963
1999 CD94/NKG2-A (KLRC1) inhibitory complex blocks CD16-triggered Syk kinase activation, tyrosine phosphorylation of CD16 zeta subunit, and downstream ERK activation in NK cells; the block operates at a PTK-dependent step by impairing Shc phosphorylation and Shc/Grb-2 complex formation. Co-engagement of CD94/NKG2-A and CD16 by antibody cross-linking, Western blot for Syk and ERK phosphorylation, Shc/Grb-2 co-immunoprecipitation Journal of immunology High 10358164
1999 CD94/NKG2-A (KLRC1) engagement with HLA-E leads to phosphorylation of the CD94/NKG2 complex and recruitment of SHP-1 to the complex, mediating inhibition of xenoreactive NK cells. Antibody blocking assays with F(ab')2 anti-CD94, phosphorylation assay, SHP-1 co-immunoprecipitation in porcine endothelial cell model Journal of immunology Medium 10570324
1999 The crystal structure of CD94 reveals a novel C-type lectin fold with a non-functional Ca2+-binding site and altered putative carbohydrate-binding site; the CD94 dimer interface reveals a putative HLA-E ligand-binding region and suggests how NKG2 interacts with CD94. X-ray crystallography at 2.6 Å resolution Immunity High 10023772
2000 CD94/NKG2-A (KLRC1) co-engagement inhibits CD69-triggered ERK activation and NK cell degranulation; specifically, CD94/NKG2-A suppresses ERK activity initiated by CD69, providing molecular evidence for cross-inhibition between activating and inhibitory receptor pathways. RBL cell transfectants expressing both CD69 and CD94/NKG2-A, degranulation assay, ERK phosphorylation Western blot, cytotoxicity assay with anti-NKG2-A blockade European journal of immunology High 10671222
2000 CD94/NKG2-C (activating isoform) transduces its triggering signal through the DAP12/KARAP ITAM-bearing adaptor molecule; engagement of CD94/NKG2-C induces MAPK phosphorylation, and the MAPK pathway participates in CD94-dependent TNF-alpha production and cytotoxicity. NK clone activation assays, MEK inhibitor (PD098059), RBL transfection with CD94/NKG2-C/DAP12, calcium mobilization, serotonin release, MAPK phosphorylation European journal of immunology High 11069065
2007 The 2.5 Å crystal structure of CD94-NKG2A heterodimer shows an asymmetric dimer interface that contrasts with homodimeric NK receptors, providing a structural basis for preferred heterodimeric assembly; mutagenesis studies identify CD94 as playing the dominant role in interacting with HLA-E compared to the NKG2A chain. X-ray crystallography at 2.5 Å resolution, structure-based mutagenesis of HLA-E and CD94-NKG2A binding interface Immunity High 18083576
2008 Subtle changes in peptide conformation within the HLA-E binding groove—not changes in HLA-E heavy chain conformation—determine differential recognition by CD94-NKG2 receptors; structural comparison of HLA-E/VMAPRALLL (poorly recognized) vs HLA-E/VMAPRTLFL (high affinity CD94-NKG2 ligand) revealed peptide conformation as the discriminating feature. X-ray crystallography of HLA-E/peptide complexes at 2.5 Å resolution Journal of molecular biology High 18339401
1997 CD94/NKG2-A (KLRC1) inhibitory receptor is involved in NK cell recognition of HLA-G1; mAbs against CD94 reconstituted cytolytic activity against HLA-G1-transfected cells, and most NK clones inhibited by HLA-G1 expressed CD94/NKG2-A. NK clone cytotoxicity assays, antibody blocking with CD94- and KIR-specific mAbs, KIR-IgG fusion protein binding assays Journal of immunology High 9190923
1997 CD94/NKG2-A (KLRC1) is the predominant inhibitory NK receptor for HLA-G used by decidual NK cells; anti-CD94 mAb prevented NK cell recognition of HLA-G transfectants, whereas mAbs against KIR receptors for HLA-C and HLA-B had no effect. NK clone cytotoxicity assays with 721.221 cells transfected with HLA-G, mAb blocking with anti-CD94 and anti-KIR antibodies Journal of immunology High 9233599
2000 HLA-E is expressed on trophoblast cells, and CD94/NKG2-A (KLRC1) on decidual NK cells binds HLA-E tetrameric complexes; the overall effect of CD94/NKG2 interaction with HLA-E is inhibition of cytotoxicity by decidual NK cells. HLA-E tetramer binding assays, antibody blocking with anti-CD94, cytotoxicity assays with decidual NK cells European journal of immunology High 10898498
1997 CD94/NKG2-A (KLRC1) inhibitory receptor modulates anti-viral and anti-tumoral responses of Vgamma9Vdelta2 T cells; anti-CD94 mAb inhibits Vgamma9Vdelta2 T cell proliferation, IFN-gamma and TNF-alpha synthesis, and cytotoxic activity. Cytokine production assays, proliferation assays, cytotoxicity assays with anti-CD94 mAb blocking Journal of immunology Medium 9550399
2004 In the absence of DAP12, NKG2A (KLRC1) is preferentially expressed at the cell surface with CD94 over NKG2C due to a single amino acid difference in the transmembrane domain; DAP12 co-expression enhances NKG2C's ability to compete for cell surface CD94 heterodimerization. Transfection of rhesus monkey NKG2A and NKG2C into COS cells with and without DAP12, flow cytometry for cell surface expression, chimeric receptor constructs Journal of immunology Medium 15153509
2005 The CD94/NKG2A (KLRC1) inhibitory receptor plays a critical role in down-regulating iNKT cell responses; IFN-gamma upregulates Qa-1b (murine HLA-E homolog) expression which in turn inhibits iNKT cell activity via CD94/NKG2A interaction; blockade of CD94/NKG2-Qa-1b interaction augments recall responses. Mouse iNKT cell stimulation with alpha-GalCer/OCH, antibody blockade of CD94/NKG2 interaction, cytokine measurement, genetic epistasis with Qa-1b Blood Medium 15746081
2002 IL-12 induces expression of NKG2-A (KLRC1) and CD94 on CD8+ T cells, and IL-12-induced expression of both subunits leads to acquisition of a functional inhibitory receptor as demonstrated in redirected killing assays; this induction was not mediated by IFN-gamma or IL-15. Cytokine stimulation of T cells, flow cytometry, redirected killing assay, RT-PCR Journal of immunology Medium 11994435
2022 CD94/NKG2 (KLRC1 product) expressed on microglial cells interacts with Qa-1 (murine HLA-E homolog) expressed in layer 6 cortical neurons to regulate activity-dependent ocular dominance plasticity; selectively targeting the Qa-1/CD94/NKG2 interaction phenocopies plasticity perturbation seen in Qa-1 knockout mice. Mouse genetic knockout (Qa-1 KO), pharmacological blockade of Qa-1/CD94-NKG2 interaction, ocular dominance plasticity assay, 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 eliminates NKG2A surface expression and overcomes HLA-E-mediated inhibition of NK cytotoxicity against solid tumor cell lines; KLRC1 KO NK cells showed significantly higher cytotoxicity against HLA-E+ tumor lines and delayed tumor progression in a xenograft mouse model; NKG2C expression was increased in KLRC1 KO NK cells. CRISPR-mediated KLRC1 gene editing, in vitro cytotoxicity assays against multiple tumor lines, xenogeneic mouse model of HLA-E+ metastatic breast cancer Frontiers in immunology High 37675109
2024 LAG-3 sustains a CD94/NKG2+ subset of exhausted CD8 T cells with enhanced cytotoxicity mediated by recognition of the stress ligand Qa-1b; loss of LAG-3 reduces this CD94/NKG2+ Tex subset, demonstrating a LAG-3-dependent circuit for NKG2 expression in T cell exhaustion. Genetic loss-of-function (LAG-3 KO), chronic viral infection mouse model, single-cell analysis, in vitro functional assays with Qa-1b blocking Cell High 39121847
2023 Antigen-specific NK cell memory against HIV and influenza is largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E; individual memory NK cells permanently acquired antigen specificity (validated by single-cell cloning), and individual HLA-E-restricted peptides constitute dominant NK cell responses in vivo. Single-cell cloning of memory NK cells, complex immunophenotyping, HLA-E peptide stimulation assays, functional memory assays Science immunology High 38064568
2023 Among 16 common classical HLA class I signal peptide (SP) variants, only 6 'functional SPs' efficiently generate epitopes enabling CD94/NKG2 engagement with HLA-E; HLA-B/-21M SP induces high HLA-E expression but provides the lowest receptor recognition and competes with other SPs, reducing overall CD94/NKG2A recognition of target cells. Systematic quantitative peptide-HLA-E binding assays, CD94/NKG2 receptor recognition functional assays, genetic population analysis Nature immunology High 37264229

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 567 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 389 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 298 10428963
2000 HLA-E is expressed on trophoblast and interacts with CD94/NKG2 receptors on decidual NK cells. European journal of immunology 290 10898498
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 250 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 118 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
2007 The heterodimeric assembly of the CD94-NKG2 receptor family and implications for human leukocyte antigen-E recognition. Immunity 81 18083576
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
2011 Clinical significance of the HLA-E and CD94/NKG2 interaction. Archivum immunologiae et therapiae experimentalis 80 21800130
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 76 39121847
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
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
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
2023 HLA class I signal peptide polymorphism determines the level of CD94/NKG2-HLA-E-mediated regulation of effector cell responses. Nature immunology 49 37264229
2023 Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis. Science immunology 49 38064568
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
2003 Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population. Genes and immunity 46 12618865
2005 IFN-gamma-mediated negative feedback regulation of NKT-cell function by CD94/NKG2. Blood 45 15746081
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
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
2023 KLRC1 knockout overcomes HLA-E-mediated inhibition and improves NK cell antitumor activity against solid tumors. Frontiers in immunology 32 37675109
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 16 31992596
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
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2004 Variable NKG2 expression in the peripheral blood lymphocytes of rhesus monkeys. Clinical and experimental immunology 12 15498028
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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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2024 A role of gut microbiota metabolites in HLA-E and NKG2 blockage immunotherapy against tumors: new insights for clinical application. Frontiers in immunology 8 39229258
2005 Ly49 and CD94/NKG2 receptor acquisition by NK cells does not require lymphotoxin-beta receptor expression. Blood 8 15827137
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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
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2023 Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder. Journal of neuroimmunology 4 37352688
2024 DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis: Perspective of Different Water Iodine Exposure. Biomedical and environmental sciences : BES 2 39401997
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