Affinage

KIR2DL4

Killer cell immunoglobulin-like receptor 2DL4 · UniProt Q99706

Length
377 aa
Mass
41.5 kDa
Annotated
2026-04-28
74 papers in source corpus 21 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

KIR2DL4 is a structurally unique killer cell immunoglobulin-like receptor on NK cells that integrates activating and inhibitory signaling to regulate innate immune responses, vascular remodeling, and cellular senescence. Its D0-D2 extracellular domain binds soluble HLA-G, which is internalized into Rab5+/Rab7+ endosomes where KIR2DL4 signals through DNA-PKcs, Akt, NF-κB, p38/JNK/ERK MAPKs, and a noncanonical JAK1–IRF7–STAT2 axis to drive IFN-γ, TNF-α, chemokine secretion, and type I interferon-stimulated gene transcription (PMID:11489965, PMID:18292514, PMID:20854369, PMID:41632833). Two structurally separable signaling modules exist: a transmembrane arginine that recruits FcεRI-γ for cytolytic and calcium responses, and a cytoplasmic ITIM that recruits SHP-1/SHP-2 for inhibitory function, with the ITIM-independent tail activating MAPKs and NF-κB even without FcεRI-γ association (PMID:12055234, PMID:15778339, PMID:18292514). Sustained KIR2DL4 activation induces a senescence-associated secretory phenotype in NK cells that promotes angiogenesis, and heparan sulfate proteoglycan interactions via the D0 domain regulate endosomal trafficking and receptor degradation (PMID:23184984, PMID:24127555).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Establishing that KIR2DL4 triggers IFN-γ rather than cytotoxicity in resting NK cells, with p38 MAPK as a required downstream kinase, defined its functional output as cytokine-biased activation.

    Evidence Redirected lysis and IFN-γ secretion assays with p38/ERK inhibitors in primary resting NK cells

    PMID:11489965

    Open questions at the time
    • Upstream events connecting receptor engagement to p38 activation unknown
    • Whether other MAPKs contribute not yet tested
  2. 2002 High

    Demonstrating that the transmembrane arginine drives activating function while the ITIM recruits SHP-1/SHP-2 for inhibition resolved how a single receptor encodes dual signaling capacity.

    Evidence Site-directed mutagenesis of ITIM tyrosine and transmembrane arginine with GST pulldown and redirected lysis in NK-like cells

    PMID:12055234

    Open questions at the time
    • Adaptor linking transmembrane arginine to activation not yet identified
    • In vivo relevance of inhibitory signaling not assessed
  3. 2003 High

    Showing that the 10A/9A frameshift polymorphism governs surface expression versus truncation explained population-level variation in KIR2DL4 function and confined surface expression to CD56bright NK cells.

    Evidence cDNA transfection of 10A/9A alleles, flow cytometry on genotyped primary NK cells

    PMID:12902476 PMID:14500636

    Open questions at the time
    • Whether the 9A truncated/soluble form retains any signaling capacity unclear
    • Mechanism restricting surface expression to CD56bright subset not defined
  4. 2005 High

    Identifying FcεRI-γ as the signaling adaptor recruited by the transmembrane arginine — distinct from DAP12 used by other activating KIRs — established KIR2DL4's unique adaptor usage and explained how it reaches the surface.

    Evidence Co-immunoprecipitation and R/G transmembrane mutation with functional cytotoxicity and cytokine assays in NK-like cell line

    PMID:15778339

    Open questions at the time
    • Whether FcεRI-γ is the sole adaptor or additional adaptors contribute
    • Stoichiometry of the receptor-adaptor complex unknown
  5. 2005 Medium

    Mapping critical HLA-G α1 domain residues (Met76, Gln79) for KIR2DL4 recognition provided the first ligand-side binding determinants.

    Evidence KIR2DL4-Fc fusion binding assays and cytotoxicity against HLA-G mutant targets

    PMID:15780179

    Open questions at the time
    • Full binding interface not structurally resolved
    • Affinity measurements not performed by biophysical methods
  6. 2008 High

    Comprehensive pathway dissection showed KIR2DL4 activates JNK, ERK, p38 MAPKs and NF-κB, and that the R/G transmembrane mutant retains MAPK/NF-κB signaling but loses FcεRI-γ-dependent cytolysis and calcium flux, proving two structurally separable signaling modules.

    Evidence Pharmacological inhibitors, phospho-Western blots, cytokine ELISA, and transmembrane mutagenesis in KHYG-1 cells

    PMID:18292514

    Open questions at the time
    • Proximal kinase linking the cytoplasmic tail to MAPK/NF-κB not identified
    • Whether the two modules cooperate or antagonize in vivo unknown
  7. 2010 High

    Discovering that KIR2DL4 primarily resides in endosomes and signals from there upon binding soluble HLA-G — via DNA-PKcs and Akt — overturned the surface-receptor paradigm and explained why soluble rather than membrane-bound HLA-G is the physiological ligand.

    Evidence Subcellular fractionation, confocal microscopy, DNA-PKcs and Akt signaling assays in primary NK cells

    PMID:20854369 PMID:22934097

    Open questions at the time
    • How soluble HLA-G accesses endosomal KIR2DL4 mechanistically not fully resolved
    • Role of DNA-PKcs versus Akt in downstream gene induction not dissected
  8. 2012 High

    Showing that sustained KIR2DL4 activation induces cellular senescence with a pro-angiogenic secretory phenotype linked the receptor to vascular remodeling programs relevant to pregnancy and tumor microenvironments.

    Evidence p21 and HP1-γ phosphorylation analysis, transcriptomics, endothelial tube formation and vascular permeability assays in primary NK cells

    PMID:23184984

    Open questions at the time
    • Whether senescence is reversible not tested
    • In vivo relevance at the decidual-placental interface not demonstrated
  9. 2013 High

    A genome-wide siRNA screen identified heparan sulfate proteoglycans (via HS3ST3B1 and syndecan-4) as regulators of KIR2DL4 endosomal trafficking and degradation through direct D0-domain binding, adding a glycan layer to receptor regulation.

    Evidence Genome-wide siRNA screen, direct binding assays with domain mutants, Rab5/Rab7 confocal co-localization, cytokine secretion assay

    PMID:24127555

    Open questions at the time
    • Which specific HS sulfation patterns are required not defined
    • Whether HSPG interaction competes with or facilitates HLA-G binding unknown
  10. 2015 High

    The 2.8 Å crystal structure revealed a D0-D2 architecture with concentration-dependent D0-mediated self-association into tetramers, and showed the D0 interface precludes canonical HLA binding, reshaping models of ligand recognition.

    Evidence X-ray crystallography, SEC, DLS, AUC, SAXS, direct HLA binding studies

    PMID:25759384

    Open questions at the time
    • No co-crystal with HLA-G obtained
    • Functional significance of tetramerization for signaling not tested
    • How self-association relates to endosomal signaling unclear
  11. 2020 Medium

    Detection of functional KIR2DL4 on mast cells, where it negatively regulates KIT and FcεRI responses and induces LIF secretion upon HLA-G stimulation, expanded its role beyond NK cells.

    Evidence Flow cytometry, agonistic antibody stimulation, cytokine/protease ELISA in LAD2 and primary PB-mast cells

    PMID:32023940

    Open questions at the time
    • Signaling pathway in mast cells not compared to NK cell pathway
    • In vivo mast cell relevance not established
    • Not independently confirmed by another lab
  12. 2026 High

    Discovery of a noncanonical JAK1–IRF7–STAT2 axis activated by soluble HLA-G via a JAK1-binding motif in KIR2DL4's cytoplasmic tail established a third signaling module driving type I ISG transcription in both CD56bright and CD56dim NK cells.

    Evidence Primary NK cell stimulation with sHLA-G, bulk/scRNA-seq, JAK1 pharmacological inhibition, co-IP of JAK1 with cytoplasmic tail truncation mutants, phospho-IRF7/STAT2 detection

    PMID:41632833

    Open questions at the time
    • How JAK1 binding is coordinated with the ITIM and FcεRI-γ modules on the same tail not resolved
    • Whether STAT2 and IRF7 form a canonical ISGF3-like complex or a distinct complex unknown
    • Physiological consequence of ISG induction for NK cell effector function not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis of KIR2DL4–HLA-G interaction (no co-crystal exists), the in vivo physiological role of endosomal signaling at the maternal-fetal interface, how the three signaling modules (FcεRI-γ, ITIM/SHP, JAK1–IRF7) are integrated or segregated on a single receptor, and the functional significance of D0-mediated oligomerization.
  • No KIR2DL4–HLA-G co-crystal structure
  • No genetic knockout or conditional deletion model in vivo
  • Integration logic among three signaling modules unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 1 R-HSA-8953854 Metabolism of RNA 1
Partners
ETS1FCER1GHLA-GJAK1PTPN11PTPN6RUNX3SDC4

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 KIR2DL4 engagement on resting NK cells induces IFN-γ production but not cytotoxicity, and this IFN-γ induction is blocked by a p38 MAPK inhibitor, placing p38 MAPK in the signaling pathway downstream of KIR2DL4. Redirected lysis assay, IFN-γ secretion assay with pharmacological inhibitors (p38 and ERK inhibitors) in resting NK cells Journal of immunology High 11489965
2002 The ITIM in KIR2DL4's cytoplasmic tail is not required for its activating function; the transmembrane arginine-tyrosine motif is required for the activation signal; the phosphorylated cytoplasmic tail recruits SHP-1 and SHP-2 (via GST pulldown), giving KIR2DL4 inhibitory potential in addition to activating function; and the activation-deficient ITIM mutant can inhibit CD16 signaling. Site-directed mutagenesis of ITIM tyrosine and transmembrane arginine, redirected lysis assay, GST fusion protein pulldown with SHP-1 and SHP-2 Journal of immunology High 12055234
2003 KIR2DL4 surface expression depends on genotype: the 10A allele (10 adenines in exon 6) encodes a full-length receptor expressed on the cell surface, while the 9A allele causes a frameshift and premature stop codon producing a non-surface-expressed, truncated receptor. Surface expression is detectable only on CD56bright NK cells from 10A carriers and is up-regulated by IL-2. cDNA transfection of 10A and 9A alleles into NK-like cell line, flow cytometry on primary NK cells, anti-KIR2DL4 mAb staining Journal of immunology High 12902476 14500636
2003 KIR2DL4 is an activating receptor: ligation of KIR2DL4 on cultured NK cells from 10A allele carriers triggers redirected lysis, confirming its activating function; this activity depends on the 10A genotype. Redirected lysis assay with anti-KIR2DL4 mAb on NK cells stratified by 9A/10A genotype Journal of immunology High 12902476
2005 KIR2DL4 associates with the Fc receptor gamma (FcεRI-γ) chain via its transmembrane arginine residue, which promotes surface expression and provides signal-transducing function. This association is distinct from other activating KIRs, which associate with DAP12. Biochemical co-immunoprecipitation, transmembrane arginine mutation (R/G), functional redirected lysis and cytokine assays in NK-like cell line Journal of immunology High 15778339
2005 Residues Met76 and Gln79 in the HLA-G α1 domain are critical for KIR2DL4 recognition; mutating these to Ala reduces binding affinity between KIR2DL4-IgG Fc fusion protein and HLA-G, and reduces KIR2DL4-transfected NK-92 cell cytolysis against HLA-G-expressing K562 targets. Retroviral transduction, KIR2DL4-IgG Fc fusion protein binding assay, cytotoxicity (LDH release) assay Cell research Medium 15780179
2005 HLA-G up-regulates expression of KIR2DL4 in antigen-presenting cells, NK cells, and T cells, suggesting a positive feedback loop where HLA-G increases expression of its own receptor. Flow cytometry and gene expression analysis of ILT2, ILT3, ILT4, and KIR2DL4 on multiple immune cell types following HLA-G exposure FASEB journal Medium 15670976
2005 The KIR2DL4 promoter drives NK cell-specific reporter expression; it contains an AML-2 binding site that acts as a repressor, and mutation of the AML site substantially increases KIR2DL4 promoter activity. KIR2DL4 also contains an inhibitory element upstream of its core promoter, distinguishing it from clonally expressed KIR promoters. Reporter gene assay in NK3.3 and primary NK cells, DNase I footprinting, site-directed mutagenesis of transcription factor binding sites Journal of immunology Medium 15778373
2007 The 9A allele of KIR2DL4 produces a secreted (soluble) form of KIR2DL4 due to splicing out of the transmembrane region; a Delta-D0 isoform missing the D0 domain is produced from some 10A allele carriers and is undetectable by available anti-KIR2DL4 mAbs. RT-PCR, flow cytometry, immunoblot analysis of NK cells from genotyped individuals; in vitro culture experiments European journal of immunology Medium 17171757
2008 KIR2DL4 cross-linking activates JNK, ERK, and p38 MAPKs, as well as the NF-κB pathway (via IKKβ phosphorylation and IκBα degradation), leading to transcription of TNF-α, IFN-γ, MIP1α, MIP1β, and IL-8. Mutation of the transmembrane arginine (R/G) abrogates FcεRI-γ association, cytolytic activity and calcium responses, but still activates MAPKs and NF-κB and selectively induces MIP1α, revealing two distinct structural signaling modules. Pharmacological kinase inhibitors, Western blotting for phosphorylated kinases, cytokine ELISA/RT-PCR, transmembrane arginine mutagenesis (R/G) in KHYG-1 NK-like cell line Journal of immunology High 18292514
2008 Epigenetic regulation of KIR2DL4 expression in T cells involves DNA methylation and histone modifications: NK cells have a fully demethylated KIR2DL4 promoter with activating histone marks (H3/H4 acetylation, di/tri-H3-K4 methylation); T cells have a partially demethylated promoter with dimethyl H3-K4 but repressive histone marks, which is sensitized to DNMT inhibitor-induced transcription with aging. Chromatin immunoprecipitation (ChIP), bisulfite sequencing, DNMT inhibitor treatment, quantitative gene expression in primary T cells and NK cells Journal of leukocyte biology Medium 18586981
2010 KIR2DL4 resides in endosomes (not at the cell surface) and signals from this intracellular site after binding soluble HLA-G; this endosomal signaling pathway involves DNA-PKcs and Akt kinases and results in a pro-inflammatory and pro-angiogenic response. Subcellular fractionation, confocal microscopy for receptor localization, signaling assays for DNA-PKcs and Akt in NK cells (review synthesizing primary data) Traffic High 20854369 22934097
2012 Sustained activation of KIR2DL4 (CD158d) by agonists induces a DNA damage response (p21 upregulation, HP1-γ phosphorylation), cellular senescence (morphological changes, survival without cell-cycle entry), and a senescence-associated secretory phenotype (SASP). The secretome of these senescent NK cells promotes vascular remodeling and angiogenesis, as measured by endothelial cell tube formation and vascular permeability assays. CD158d agonist stimulation of primary NK cells, Western blot for p21 and HP1-γ phosphorylation, flow cytometry, transcriptome analysis, functional vascular assays (tube formation, permeability) PNAS High 23184984
2012 The KIR2DL4 promoter requires Runx binding sites (specifically Runx3) for constitutive transcription, with contributions from CRE and initiator elements; IL-2/IL-15 stimulation additionally requires functional Ets (Ets1) sites. Runx3 and Ets1 were shown by ChIP to bind the 2DL4 promoter in situ. Promoter mutagenesis, EMSA, co-transfection assay, chromatin immunoprecipitation (ChIP) in NK cell lines and T cells Journal of immunology High 22467658
2013 KIR2DL4 directly interacts with heparan sulfate (HS)/heparin via its D0 domain (identified by genome-wide siRNA screen for HS3ST3B1); this interaction induces differential localization to Rab5+ and Rab7+ endosomes and downregulates cytokine production and receptor degradation. Syndecan-4 (SDC4) HSPG directly affects KIR2DL4 endocytosis and membrane trafficking. Genome-wide siRNA screen, direct binding assays with KIR2DL4 domain mutants, confocal microscopy for endosomal co-localization (Rab5/Rab7), cytokine secretion assay Journal of immunology High 24127555
2015 Crystal structure of KIR2DL4 extracellular domains determined at 2.8 Å reveals a D0-D2 arrangement (lacking D1) with C2-type immunoglobulin folds at an acute elbow angle. KIR2DL4 self-associates via the D0 domain in a concentration-dependent manner, forming tetramers in the crystal lattice and in solution (confirmed by SEC, DLS, AUC, SAXS). This D0-mediated self-association precludes an HLA interaction analogous to KIR3DL1, and no direct HLA binding was detected. X-ray crystallography (2.8 Å), size exclusion chromatography, dynamic light scattering, analytical ultracentrifugation, small angle X-ray scattering, direct HLA binding studies Journal of biological chemistry High 25759384
2020 KIR2DL4 is expressed on human mast cells (LAD2, PB-mast) in addition to NK cells; agonistic antibodies to KIR2DL4 negatively regulate KIT-mediated and FcεRI-mediated responses of mast cells, and HLA-G stimulation through KIR2DL4 induces secretion of leukemia inhibitory factor and serine proteases from mast cells. Flow cytometry, agonistic antibody stimulation assays, ELISA for cytokine/protease secretion in human mast cell lines and primary PB-mast cells International journal of molecular sciences Medium 32023940
2021 HLA-G binding to KIR2DL4 on NK cells desensitizes NK cells to trastuzumab-mediated ADCC in HER2+ breast cancer; KIR2DL4 (without HLA-G engagement) promotes ADCC and synergizes with Fcγ receptor to increase IFN-γ secretion; IFN-γ upregulates KIR2DL4 via JAK2/STAT1 signaling; blockade of HLA-G/KIR2DL4 signaling improves trastuzumab efficacy in vivo. NK cell cytotoxicity assays, ELISA for cytokines, pharmacological JAK2/STAT1 inhibition, KIR2DL4 blockade in vivo mouse xenograft model Signal transduction and targeted therapy Medium 34158475
2022 KIR2DL4 expressed in renal cell carcinoma (RCC) cells promotes RCC proliferation associated with PI3K/Akt signaling activation; KIR2DL4 knockdown reduces AKT phosphorylation and proliferation, while KIR2DL4 overexpression increases AKT phosphorylation and tumor growth in vivo. shRNA knockdown, overexpression, MTT assay, soft agar colony formation, xenograft mouse model, RNA sequencing, immunoblot for phospho-AKT, PI3K inhibitor (wortmannin) treatment Life sciences Medium 35063466
2026 Soluble HLA-G stimulates transcription of type I interferon-stimulated genes (ISGs) in primary NK cells through a noncanonical pathway requiring the transcription factor IRF7 and kinase JAK1. The C-terminal portion of KIR2DL4's cytoplasmic tail contains a JAK1-binding sequence analogous to IFN receptor conserved JAK1 binding sites, and was required for JAK1 binding to KIR2DL4. HLA-G stimulation led to nuclear phosphorylation of IRF7 and STAT2. scRNA-seq showed ISG induction is similar in CD56bright and CD56dim NK cells. Primary NK cell stimulation with soluble HLA-G and agonistic anti-KIR2DL4 antibody, transcriptomics (bulk RNA-seq, scRNA-seq), pharmacological JAK1 inhibition, co-immunoprecipitation of JAK1 with KIR2DL4 cytoplasmic tail mutants, nuclear phospho-IRF7 and phospho-STAT2 detection Science signaling High 41632833

Source papers

Stage 0 corpus · 74 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 HLA-G up-regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 244 15670976
2002 KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. Journal of immunology (Baltimore, Md. : 1950) 191 12055234
2001 Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells. Journal of immunology (Baltimore, Md. : 1950) 188 11489965
2012 KIR2DL4 (CD158d): An activation receptor for HLA-G. Frontiers in immunology 150 22934097
2003 KIR2DL4 is an IL-2-regulated NK cell receptor that exhibits limited expression in humans but triggers strong IFN-gamma production. Journal of immunology (Baltimore, Md. : 1950) 138 14500636
2012 Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling. Proceedings of the National Academy of Sciences of the United States of America 137 23184984
2005 Cutting edge: KIR2DL4 transduces signals into human NK cells through association with the Fc receptor gamma protein. Journal of immunology (Baltimore, Md. : 1950) 111 15778339
2003 KIR2DL4 (CD158d) genotype influences expression and function in NK cells. Journal of immunology (Baltimore, Md. : 1950) 96 12902476
2021 Interaction between HLA-G and NK cell receptor KIR2DL4 orchestrates HER2-positive breast cancer resistance to trastuzumab. Signal transduction and targeted therapy 88 34158475
2005 Residues Met76 and Gln79 in HLA-G alpha1 domain involve in KIR2DL4 recognition. Cell research 76 15780179
2005 Three structurally and functionally divergent kinds of promoters regulate expression of clonally distributed killer cell Ig-like receptors (KIR), of KIR2DL4, and of KIR3DL3. Journal of immunology (Baltimore, Md. : 1950) 67 15778373
2005 The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated. European journal of immunology 66 15580659
2007 Three common alleles of KIR2DL4 (CD158d) encode constitutively expressed, inducible and secreted receptors in NK cells. European journal of immunology 54 17171757
2003 Recognition of HLA-G by the NK cell receptor KIR2DL4 is not essential for human reproduction. European journal of immunology 52 12616484
2010 Endosomal signaling and a novel pathway defined by the natural killer receptor KIR2DL4 (CD158d). Traffic (Copenhagen, Denmark) 46 20854369
2007 Possible roles of KIR2DL4 expression on uNK cells in human pregnancy. American journal of reproductive immunology (New York, N.Y. : 1989) 46 17362384
2002 Alleles of the KIR2DL4 receptor and their lack of association with pre-eclampsia. European journal of immunology 44 11754000
2003 Different and divergent regulation of the KIR2DL4 and KIR3DL1 promoters. Journal of immunology (Baltimore, Md. : 1950) 43 12794136
2000 Detection of KIR2DL4 alleles by sequencing and SSCP reveals a common allele with a shortened cytoplasmic tail. Tissue antigens 40 11034561
2013 Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: heparan sulfate directly modulates KIR2DL4-mediated responses. Journal of immunology (Baltimore, Md. : 1950) 36 24127555
2015 The structure of the atypical killer cell immunoglobulin-like receptor, KIR2DL4. The Journal of biological chemistry 33 25759384
2008 KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules. Journal of immunology (Baltimore, Md. : 1950) 31 18292514
2022 Roles of HLA-G/KIR2DL4 in Breast Cancer Immune Microenvironment. Frontiers in immunology 28 35185887
2008 Epigenetic mechanisms of age-dependent KIR2DL4 expression in T cells. Journal of leukocyte biology 28 18586981
2004 Investigation of killer cell immunoglobulinlike receptor gene diversity: I. KIR2DL4. Human immunology 28 14700593
2015 Genetic polymorphisms and expression of HLA-G and its receptors, KIR2DL4 and LILRB1, in non-small cell lung cancer. Tissue antigens 27 25855135
2009 The genotype of the NK cell receptor, KIR2DL4, influences INFgamma secretion by decidual natural killer cells. Molecular human reproduction 25 19509110
2008 Human leukocyte antigen-G, a ligand for the natural killer receptor KIR2DL4, is expressed by eutopic endometrium only in the menstrual phase. Fertility and sterility 21 18314122
2020 Possible roles of HLA-G regulating immune cells in pregnancy and endometrial diseases via KIR2DL4. Journal of reproductive immunology 20 32711226
2016 Possible Role of HLA-G, LILRB1 and KIR2DL4 Gene Polymorphisms in Spontaneous Miscarriage. Archivum immunologiae et therapiae experimentalis 20 26973020
2009 Possible gene-gene interaction of KIR2DL4 with its cognate ligand HLA-G in modulating risk for preeclampsia. Reproductive sciences (Thousand Oaks, Calif.) 18 19700612
2005 Genomic characterization of KIR2DL4 in families and unrelated individuals reveals extensive diversity in exon and intron sequences including a common frameshift variation occurring in several alleles. Tissue antigens 18 15853895
2009 Evidence for balancing selection acting on KIR2DL4 genotypes in rhesus macaques of Indian origin. Immunogenetics 17 19506858
2020 Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis. International journal of molecular sciences 15 32023940
2013 KIR2DL4 copy number variation is associated with CD4+ T-cell depletion and function of cytokine-producing NK cell subsets in SIV-infected Mamu-A*01-negative rhesus macaques. Journal of virology 13 23449795
2006 Investigation of killer cell immunoglobulin-like receptor KIR2DL4 diversity by sequence-based typing in Chinese population. Tissue antigens 13 16573558
2006 Rapid production of human KIR2DL4 extracellular domain and verification of its interaction with HLA-G. Biochemistry. Biokhimiia 12 16487070
2022 KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation. Life sciences 10 35063466
2017 The Influence of Cytomegalovirus on Expression of HLA-G and its Ligand KIR2DL4 by Human Peripheral Blood Leucocyte Subsets. Scandinavian journal of immunology 10 28817184
2011 Lack of KIR2DL4 gene in a fertile Caucasian woman. Tissue antigens 10 21623736
2007 Allelic diversity in KIR2DL4 in a bone marrow transplant population: description of three novel alleles. Tissue antigens 10 17610421
2007 The elucidation of KIR2DL4 gene polymorphism. Molecular immunology 10 18082267
2018 KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects. Molecular immunology 8 30482463
2012 Differential transcription factor use by the KIR2DL4 promoter under constitutive and IL-2/15-treated conditions. Journal of immunology (Baltimore, Md. : 1950) 8 22467658
2015 Genetic polymorphism of KIR2DL4 in the Polish population. Tissue antigens 7 25818657
2014 Two new cases of KIR3DP1, KIR2DL4-negative genotypes, one of which is also lacking KIR3DL2. Archivum immunologiae et therapiae experimentalis 7 25033772
2009 High levels of molecular polymorphism at the KIR2DL4 locus in French and Congolese populations: impact for anthropology and clinical studies. Human immunology 7 19679155
2007 Enrichment of individual KIR2DL4 sequences from genomic DNA using long-template PCR and allele-specific hybridization to magnetic bead-bound oligonucleotide probes. Tissue antigens 7 17498270
2024 Combined maternal KIR2DL4 and fetal HLA-G polymorphisms were associated with preeclampsia in a Han Chinese population. Frontiers in genetics 6 39144721
2007 Cloning and sequencing alleles of the KIR2DL4 gene from genomic DNA samples. Tissue antigens 6 17445175
2023 KIR2DL4/HLA-G polymorphisms were associated with HCV infection susceptibility among Chinese high-risk population. Journal of medical virology 5 36890645
2013 Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G, does not influence susceptibility to asthma. Tissue antigens 5 24033084
2009 KIR2DL4 (CD158d) polymorphisms and susceptibility to multiple sclerosis. Journal of neuroimmunology 5 19304328
2023 The effects of KIR2DL4 stimulated NK-92 cells on the apoptotic pathways of HER2 + /HER-breast cancer cells. Medical oncology (Northwood, London, England) 4 37027073
2020 Expression of HLA-G and KIR2DL4 receptor in chorionic villous in missed abortion. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 3 33305671
2021 KIR2DL4 genetic diversity in a Brazilian population sample: implications for transcription regulation and protein diversity in samples with different ancestry backgrounds. Immunogenetics 2 33595694
2025 Emerging roles of KIR2DL4 in cancer immunotherapy. Breast cancer (Tokyo, Japan) 1 40549069
2016 Description of the novel KIR2DL4*035 allele identified using high-throughput sequencing. HLA 1 26917249
2015 KIR2DL4 expression rather than its single nucleotide polymorphisms correlates with pre-eclampsia. International journal of clinical and experimental pathology 1 26823774
2026 The fetal trophoblast cell marker HLA-G activates a type I interferon response in primary NK cells through the receptor KIR2DL4. Science signaling 0 41632833
2025 Mechanism of microRNA-152 Regulating Decidual Natural Killer Cell Viability and Affecting Trophoblast Cell Invasiveness via the HLA-G/KIR2DL4 Axis. The Kaohsiung journal of medical sciences 0 40309956
2022 Modularisation of published and novel models toward a complex KIR2DL4 pathway in pbNK cell. MethodsX 0 35774414
2022 The novel KIR2DL4*00108 allele identified by sequencing-based typing in a Chinese Han individual. HLA 0 36256498
2020 Quantitative Multiplex Real-Time Reverse Transcriptase-Polymerase Chain Reaction with Fluorescent Probe Detection of Killer Immunoglobulin-Like Receptors, KIR2DL4/3DL3. Diagnostics (Basel, Switzerland) 0 32823754
2019 Description of the novel KIR2DL4*00603 allele identified in a Chinese Hani individual. HLA 0 31041847
2019 Characterization of the novel KIR2DL4*037 allele identified in a Chinese Hani individual. HLA 0 31044496
2019 Identification of the novel KIR2DL4*036 allele in a Chinese Hani individual. HLA 0 31069992
2019 The novel KIR2DL4*038 allele identified by sequencing-based typing in a Chinese Naxi individual. HLA 0 31070014
2018 Description of the novel KIR2DL4*039 allele identified in a southern Chinese Han individual. HLA 0 29292865
2018 Identification of the novel KIR2DL4*040 allele in a southern Chinese Han individual. HLA 0 29316382
2018 [Association of polymorphisms of KIR2DL4 gene with leukemia among ethnic Hans from southern China]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 29419875
2018 Identification of the novel KIR2DL4*00106 allele in a southern Chinese Han individual. HLA 0 29577675
2017 [Allelic diversity of KIR2DL4 gene and identification of five novel alleles among southern Han Chinese population]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 0 28397235
2016 Identification of the novel KIR2DL4*00503 allele from a southern Chinese Han individual. HLA 0 27748071