Affinage

LY9

T-lymphocyte surface antigen Ly-9 · UniProt Q9HBG7

Length
655 aa
Mass
72.1 kDa
Annotated
2026-04-28
59 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LY9 (CD229/SLAMF3) is a SLAM family immunoreceptor that engages in homophilic interactions through its N-terminal Ig domain and functions as both a co-stimulatory and inhibitory receptor depending on cell context, regulating T cell activation, iNKT cell development, innate-like B cell homeostasis, and autoimmunity. Its cytoplasmic tail recruits SAP/SH2D1A at phosphotyrosine-based motifs, enabling SAP-mediated FynT kinase activation, while a distinct tyrosine (Y606) recruits Grb2 to control clathrin/AP-2-dependent endocytosis via the Y470EKL motif and attenuate TCR–ERK signaling (PMID:11389028, PMID:15096483, PMID:15879090, PMID:12621057). In lymphocytes, LY9 restrains IFN-γ production, Th2 cytokines, iNKT lineage differentiation, marginal zone B cell expansion, and autoantibody generation, as demonstrated by Ly9-knockout mice that develop spontaneous anti-nuclear antibodies and dysregulated lymphocyte subsets (PMID:16365421, PMID:23914190, PMID:26667173, PMID:28980301). Autosomal recessive LY9 deficiency in humans selectively impairs TH1* cell IFN-γ production and confers susceptibility to tuberculosis, with LY9 polarizing naïve CD4+ T cells toward TH1* fate via SAP-dependent T-bet induction and SAP-independent RORγT induction (PMID:40446017). In multiple myeloma cells, homotypic LY9 self-ligation activates a SHP2–GRB2–RASAL3–RAS/ERK proliferative signaling axis (PMID:31974290, PMID:36445333).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2001 High

    Identifying the first intracellular effector of LY9 established that it signals through the SAP/SH2D1A adaptor at phosphotyrosine motifs, linking it to the XLP disease pathway shared by other SLAM receptors.

    Evidence Yeast two-hybrid and co-immunoprecipitation in COS cells and lymphoid cells showing phosphotyrosine-dependent SAP recruitment

    PMID:11389028

    Open questions at the time
    • Specific tyrosine residues for SAP binding not individually mapped
    • Downstream signaling consequences of SAP recruitment to LY9 not yet determined
  2. 2003 High

    Discovery that LY9 uniquely among SLAM family members undergoes clathrin-dependent endocytosis via an AP-2 binding motif (Y470EKL) revealed a distinct mechanism for regulating its surface expression.

    Evidence Co-immunoprecipitation of endogenous AP-2, Y470A mutagenesis abolishing internalization, and TCR/BCR coligation assays in T and B cell lines

    PMID:12621057

    Open questions at the time
    • Whether AP-2-mediated endocytosis modulates signaling output or merely controls receptor abundance was unclear
    • Structural basis of AP-2/LY9 interaction not resolved
  3. 2004 High

    Demonstrating that SAP bridges LY9 to FynT kinase activation explained how SAP recruitment translates into downstream phosphorylation signaling, and that SAP is required for LY9 phosphorylation itself.

    Evidence In vitro kinase assays showing SAP relief of FynT autoinhibition, SAP R78E mutagenesis, and thymocyte phosphorylation assays

    PMID:15096483

    Open questions at the time
    • Whether FynT is the sole kinase downstream of LY9–SAP was not established
    • Downstream substrates of FynT activated via LY9 were not identified
  4. 2005 High

    Mapping the homophilic binding interface and showing immune synapse recruitment resolved how LY9 is engaged during antigen-dependent cell–cell contact, establishing it as a self-ligand receptor at the T–B interface.

    Evidence Soluble Ig fusion binding assays, alanine-scanning mutagenesis of N-terminal domain charged residues, and confocal imaging of T–B conjugates

    PMID:15905546

    Open questions at the time
    • Crystal structure of the homophilic dimer was not available
    • Signaling consequences of synapse recruitment were not directly measured
  5. 2005 High

    Identification of Grb2 as a second cytoplasmic adaptor binding Y606 — distinct from SAP sites — and its role in controlling endocytosis and attenuating TCR–ERK signaling revealed a dual-adaptor signaling logic for LY9.

    Evidence Co-immunoprecipitation, Y606 mutagenesis, dominant-negative Grb2 expression impairing internalization, and NFAT-luciferase reporter attenuation

    PMID:15879090

    Open questions at the time
    • How SAP and Grb2 binding are coordinated or compete at the receptor was unknown
    • Identity of downstream Grb2 effectors in the LY9 context not mapped
  6. 2006 High

    The first Ly9-knockout mouse established that LY9 has non-redundant functions in T cell activation and Th2 cytokine production distinct from SLAM and SAP deficiency phenotypes.

    Evidence Ly9−/− mouse with reduced IL-4 and IL-2 production upon suboptimal TCR stimulation, compared to SLAM−/− and SAP−/− mice

    PMID:16365421

    Open questions at the time
    • Whether the in vivo phenotype reflects costimulatory or inhibitory function was ambiguous
    • In vivo infection phenotypes were modest
  7. 2012 High

    Genetic epistasis experiments revealed that LY9 negatively regulates iNKT and innate memory-like CD8+ T cell development in the thymus through an IL-4-dependent mechanism, establishing its inhibitory role in innate-like lymphocyte fate.

    Evidence Ly9−/− mice showing expanded innate CD8+ T cells rescued by IL4Rα co-deletion; anti-Ly9 mAb suppressing α-GalCer-induced IL-4 in vivo

    PMID:23225888

    Open questions at the time
    • Signaling pathway downstream of LY9 that restrains iNKT differentiation was not identified
    • Cell-intrinsic vs. cell-extrinsic effects not fully delineated
  8. 2013 High

    Spontaneous autoantibody production and germinal center expansion in Ly9−/− mice on multiple backgrounds established LY9 as an inhibitory checkpoint restraining humoral autoimmunity, paralleling the human SLE-linked locus.

    Evidence Ly9−/− mice on B6.129 and BALB/c.129 backgrounds with anti-nuclear/anti-dsDNA autoantibodies, expanded Tfh and GC B cells, and in vitro suppression of IFN-γ by LY9 ligation

    PMID:23914190

    Open questions at the time
    • Molecular mechanism by which LY9 suppresses Tfh expansion was not defined
    • Whether human LY9 deficiency causes lupus was unknown
  9. 2015 High

    Demonstrating that Ly9 deficiency expands marginal zone and B1a B cells while anti-Ly9 mAb selectively eliminates MZ B cells by downregulating the CD19/CD21/CD81 complex connected LY9 to innate-like B cell homeostasis and suggested therapeutic utility.

    Evidence Ly9−/− mouse B cell subset analysis, anti-Ly9 mAb in vivo administration depleting MZ B cells Fc-independently, TNP-Ficoll immunization

    PMID:26667173

    Open questions at the time
    • Mechanism linking LY9 signaling to CD19 complex downregulation was not defined
    • Whether MZ B cell depletion is direct or indirect was unclear
  10. 2015 Medium

    The SLE-associated Val602 variant's reduced SAP binding affinity provided a molecular explanation for how a common LY9 polymorphism modulates immune function and disease risk.

    Evidence Binding affinity comparison of Val602 vs Met602 for SAP, with diminished CD69 upregulation in Val602-expressing T cells

    PMID:26221972

    Open questions at the time
    • Single-lab finding not yet replicated independently
    • In vivo relevance of two-fold affinity difference for autoimmune phenotype not tested
  11. 2016 Medium

    Discovery that SLAMF3 costimulation upregulates CD25 through Smad3, enhancing IL-2R/STAT5 signaling and Treg differentiation, added a costimulatory/tolerogenic axis to LY9 function.

    Evidence SLAMF3 ligation on CD4+ T cells with Smad3 pathway inhibition, STAT5 phosphorylation, and Treg differentiation assays

    PMID:27482100

    Open questions at the time
    • Single-lab finding
    • How Smad3 activation connects to a transmembrane receptor lacking TGF-β receptor features is unexplained
    • In vivo Treg relevance not tested
  12. 2016 Medium

    In hepatocellular carcinoma, SLAMF3 overexpression was shown to suppress proliferation through RB hypophosphorylation, E2F inactivation, and PLK1 repression, and to reduce MRP-1-mediated drug resistance, revealing a tumor suppressor axis in epithelial cells.

    Evidence SLAMF3 overexpression in HCC cell lines with Western blot for pRB/PLK1, E2F reporter, MRP-1 expression, and drug sensitivity assays

    PMID:26799423 PMID:27081035

    Open questions at the time
    • Single-lab findings for both RB–E2F and MRP-1 axes
    • How a lymphocyte receptor activates the RB pathway in hepatocytes is mechanistically unexplained
    • Loss-of-function validation in HCC not performed
  13. 2017 High

    Refined analysis of iNKT subsets in Ly9−/− mice showed selective expansion of NKT2 with loss of NKT1, and agonistic anti-Ly9 mAb recapitulated inhibition, demonstrating lineage-specific control of iNKT differentiation.

    Evidence Ly9−/− mice on BALB/c and C57BL/6 backgrounds, iNKT subset flow cytometry, agonistic mAb reducing iNKT cytokine production

    PMID:28980301

    Open questions at the time
    • Downstream signaling pathway from LY9 that biases NKT1 vs NKT2 fate not identified
    • Whether SAP or Grb2 arm mediates this effect unknown
  14. 2020 High

    In myeloma cells, identification of the SLAMF3–SHP2–GRB2–ERK signaling axis activated by homotypic self-ligation explained how LY9 overexpression promotes MM proliferation, contrasting with its inhibitory role in normal lymphocytes.

    Evidence Co-immunoprecipitation of endogenous SHP2/GRB2 with SLAMF3, cytoplasmic domain truncation, SHP2 inhibitor treatment, ERK phosphorylation in MM cell lines

    PMID:31974290

    Open questions at the time
    • How SHP2 switches from a phosphatase to a proliferative effector in the SLAMF3 context was not resolved
    • Whether SAP participates in MM signaling was not tested
  15. 2022 Medium

    Identification of RASAL3 as a LY9-interacting partner in MM cells extended the oncogenic signaling model to include RAS GTPase regulation downstream of homotypic LY9 activation.

    Evidence Co-IP/mass spectrometry identifying RASAL3, co-culture phosphorylation assays, in vivo xenograft with CD229 overexpression

    PMID:36445333

    Open questions at the time
    • Single-lab Co-IP/MS identification not independently confirmed
    • Whether RASAL3 interaction occurs in normal lymphocytes unknown
    • Structural basis of SLAMF3–RASAL3 interaction not defined
  16. 2025 High

    Human autosomal recessive LY9 deficiency was shown to cause selective TH1* cell dysfunction and tuberculosis susceptibility, with mechanistic dissection revealing SAP-dependent T-bet induction and SAP-independent RORγT induction as parallel pathways through which LY9 polarizes CD4+ T cells.

    Evidence Human patients with LY9 loss-of-function, ex vivo T cell assays, siRNA/inhibitor dissection separating SAP and RORγT axes, NFAT1 reporter for IFN-γ enhancement

    PMID:40446017

    Open questions at the time
    • Number of identified kindreds is small
    • How LY9 activates RORγT independently of SAP is mechanistically undefined
    • Whether LY9 deficiency affects other infectious disease susceptibilities beyond TB is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of the LY9 homophilic dimer, how the SAP-dependent and Grb2-dependent signaling arms are integrated at the receptor to produce context-dependent activating versus inhibitory outcomes, and the mechanism by which LY9 induces RORγT independently of SAP.
  • No crystal or cryo-EM structure of the LY9 extracellular homophilic complex
  • Molecular basis for context-dependent activating (MM) vs inhibitory (T cell) signaling unknown
  • SAP-independent RORγT induction pathway completely undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 5 GO:0001618 virus receptor activity 1
Partners
AP2M1FYNGRB2PTPN11RASAL3SH2D1A

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 LY9 (Ly-9) cytoplasmic tail recruits the SAP/SH2D1A protein; recruitment is most efficient when specific tyrosine residues in the cytoplasmic tail of Ly-9 are phosphorylated. Interactions were demonstrated by yeast two-hybrid, COS cell transfections, and in lymphoid cells. Yeast two-hybrid, COS cell transfection co-immunoprecipitation, lymphoid cell assays Blood High 11389028
2004 SAP is required for phosphorylation of Ly9 in thymocytes and peripheral T cells. SAP binds directly to FynT (via both SH3 and kinase domains) and to Lck (via kinase domain only), and SAP addition to autoinhibited FynT causes a large increase in FynT catalytic activity, bridging SLAM/Ly9 with Src-like PTKs. SAP mutant R78E, unable to bind FynT SH3 domain, neither increases FynT activity nor functions as an adaptor. In vitro protein interaction assays, yeast two-hybrid, in vitro kinase activity assay, SAP mutant transfection into T cells, thymocyte phosphorylation assays International immunology High 15096483
2005 CD229 (LY9) interacts homophilically through its N-terminal Ig domain; charged residues E27, E29 (B-C loop) and R89 (F-G loop) are required for homophilic adhesion, while R44A enhances it. CD229 relocalizes to the immunological synapse during antigen-dependent T–B cell contact. Soluble Ig fusion protein binding assays on transfected cells, domain deletion mutants, alanine-substitution mutagenesis, confocal microscopy of immune synapse Journal of immunology High 15905546
2005 CD229 interacts with Grb2 in a phosphorylation-dependent manner via the SH2 domain of Grb2 and tyrosine Y606 in CD229 cytoplasmic tail; this site is distinct from the two tyrosines required for SAP recruitment. Grb2 binding controls CD229 internalization (endocytosis is impaired when the Grb2-binding Y606 site is mutated or when dominant-negative Grb2 is expressed). CD229 ligation partially attenuates TCR signaling and ERK phosphorylation. Co-immunoprecipitation from T lymphocytes and transfected cells, site-directed mutagenesis (Y606), dominant-negative Grb2 expression, NFAT-luciferase reporter assay, internalization assays Journal of immunology High 15879090
2003 CD229 interacts with the mu2 chain of the AP-2 clathrin adaptor complex via the Y470EKL motif in its cytoplasmic tail, mediating clathrin-dependent endocytosis. This AP-2 binding site is distinct from the SAP recruitment sites. CD229 surface expression is also regulated differentially by TCR and BCR coligation, which accelerate endocytosis; on B cells, Fcγ receptors control CD229 cell surface expression. CD229 is the only CD150 family member associated with AP-2. Co-immunoprecipitation of endogenous AP-2, site-directed mutagenesis (Y470A), antibody ligation internalization assays in T and B cell lines, F(ab')2 vs intact antibody comparison Journal of Biological Chemistry High 12621057
2006 Ly9-deficient mice show reduced IL-4 production (Th2 defect) and impaired T cell proliferation and IL-2 production after suboptimal anti-CD3 stimulation, distinct from SLAM−/− and SAP−/− phenotypes. Ly9−/− macrophages show no cytokine or bacterial killing defects unlike SLAM−/− macrophages, and NKT cell development is normal unlike SAP−/− mice. Ly9-knockout mouse generation, in vitro T cell stimulation assays, cytokine ELISA, NKT development flow cytometry, viral infection (LCMV) challenge Journal of immunology High 16365421
2012 Ly9 negatively regulates the development of thymic innate memory-like CD8+ T cells and invariant NKT cells. Ly9-deficient mice have an expanded thymic innate CD8+ population dependent on IL-4 signaling (shown by Ly9−/−IL4ra−/− double knockout rescue). Anti-Ly9 mAb inhibits IL-4 levels induced by α-galactosylceramide injection in wild-type mice. Ly9-knockout mouse analysis, flow cytometry, gene expression profiling, Ly9−/−IL4ra−/− double knockout, anti-Ly9 mAb administration, α-galactosylceramide challenge Journal of immunology High 23225888
2013 Ly9-deficient mice spontaneously develop anti-nuclear antibodies, anti-dsDNA, and anti-nucleosome autoantibodies on multiple genetic backgrounds. Aged Ly9−/− mice show expansion of T follicular helper and germinal center B cells. In vitro, Ly9 acts as an inhibitory receptor suppressing IFN-γ production by CD4+ T cells. Ly9-knockout mouse (B6.129 and BALB/c.129 backgrounds), autoantibody ELISA, flow cytometry of lymphocyte subsets, in vitro CD4+ T cell stimulation/cytokine assay Frontiers in immunology High 23914190
2015 Ly9-deficient mice have expanded splenic marginal zone (MZ), B1a, and transitional 1 B cells with elevated IgG3 natural antibodies and enhanced T-independent type II antibody responses. Anti-Ly9 mAb selectively eliminates splenic MZ B cells and downregulates the CD19/CD21/CD81 complex, impairing B cell survival and activation in an Fc-independent manner. Ly9-knockout mouse analysis, in vivo anti-Ly9 mAb administration, flow cytometry of B cell subsets, serum Ig ELISA, immunization with TNP-Ficoll Journal of immunology High 26667173
2015 The SLE-associated Val602 variant of CD229 (rs509749) has approximately two-fold lower affinity for SAP compared with the Met602 variant, and cells expressing Val602 show diminished T cell activation (CD69 upregulation) compared with Met602-expressing cells. Binding affinity comparison (surface plasmon resonance implied), T cell line activation assays (CD69 upregulation), comparison of Val602 vs Met602 CD229 variants Immunology Medium 26221972
2017 Ly9 (SLAMF3) negatively regulates iNKT cell lineage differentiation in the thymus: Ly9-deficient BALB/c mice have expanded NKT2 and nearly absent NKT1 thymic cells. Anti-Ly9 agonistic mAb in wild-type mice impairs IL-4 and IFN-γ production by iNKT cells and reduces splenic iNKT numbers, with selective decrease in NKT2 cells. Ly9-knockout mouse flow cytometry analysis on BALB/c and C57BL/6 backgrounds, agonistic anti-Ly9 mAb in vivo administration, intracellular cytokine staining European journal of immunology High 28980301
2011 CD229 (LY9) is overexpressed on myeloma cells including CD138-negative myeloma precursor cells. siRNA-mediated downregulation of CD229 reduces viable myeloma cell numbers and clonal colony formation, and enhances anti-tumor activity of chemotherapeutics. Targeting CD229 with a monoclonal antibody results in complement- and cell-mediated lysis. Antibody array for phosphorylated immunoreceptors, siRNA knockdown, clonogenic assay, ADCC/CDC assays, flow cytometry, RT-PCR, Western blot, IHC Haematologica Medium 21606160
2020 CD229 CAR T cells eliminate MM plasma cells and MM-propagating cells. CD229 is downregulated in T cells during activation, preventing fratricide during CAR T cell production; CAR T cells spare CD229neg/low functional T cells while targeting CD229high cells. CAR T cell engineering, in vitro cytotoxicity assays, in vivo MM mouse model, flow cytometry of CD229 expression during T cell activation Nature communications Medium 32034142
2020 SLAMF3 (CD229/LY9) interacts directly with adaptor proteins SHP2 and GRB2 (which also interact with each other) in MM cells. SLAMF3 knockdown/knockout and cytoplasmic-domain truncation decrease phosphorylated ERK levels. Self-ligand homotypic interaction between MM cells activates the SLAMF3–SHP2–GRB2–ERK pathway, promoting MM cell proliferation. Co-immunoprecipitation, SLAMF3 KD/KO, cytoplasmic domain truncation mutant (ΔSLAMF3), SHP2 inhibitor treatment, ERK phosphorylation Western blot, proliferation assays Molecular cancer research High 31974290
2022 CD229 promotes MM cell proliferation by activating the RAS/ERK signaling pathway through interaction with RASAL3 (a RAS GTPase-activating protein). Co-immunoprecipitation coupled with mass spectrometry identified RASAL3 as a CD229-interacting protein; intercellular tyrosine phosphorylation mediates self-activation of CD229, which then activates RAS/ERK via RASAL3. Co-immunoprecipitation coupled with mass spectrometry, co-culture with immunofluorescence, CD229 overexpression, in vivo xenograft mouse model, ERK signaling assays Aging Medium 36445333
2014 SLAMF3 (CD229) expressed on hepatocytes interacts with HCV envelope protein E2 and participates in HCV entry. The first N-terminal extracellular domain is essential for interaction with HCV particles. siRNA knockdown and anti-SLAMF3 blocking antibodies decreased hepatocyte susceptibility to HCV infection; SLAMF3 overexpression increased susceptibility. siRNA knockdown, SLAMF3-blocking antibodies, recombinant E2 binding assay, peptide domain mapping, infection susceptibility assays PloS one Medium 24927415
2016 SLAMF3 (LY9) costimulation of CD4+ T cells enhances sensitivity to IL-2 by upregulating CD25 through a Smad3-dependent mechanism, augmenting IL-2/IL-2R/STAT5 pathway activation and promoting regulatory T cell (Treg) differentiation from naïve CD4+ T cells. SLAMF3 ligation on CD4+ T cells, CD25 upregulation assay, Smad3 pathway inhibition, STAT5 phosphorylation assay, Treg differentiation flow cytometry Proceedings of the National Academy of Sciences Medium 27482100
2025 Autosomal recessive LY9 deficiency in humans causes selective impairment of IFN-γ production by TH1* (CCR4-CCR6+CXCR3+T-bet+RORγT+) CD4+ T cells, underlying tuberculosis susceptibility. LY9 polarizes naïve CD4+ T cells toward TH1* memory cells by inducing T-bet via SAP and by inducing RORγT independently of SAP. LY9 costimulation enhances TCR-driven IFN-γ production of memory TH1* cells via NFAT1 and RORγT. Human genetic analysis (autosomal recessive LY9 deficiency patients), ex vivo T cell functional assays, LY9 costimulation experiments, siRNA/inhibitor dissection of SAP and RORγT pathways, NFAT1 reporter assays Science immunology High 40446017
2011 Human cytomegalovirus UL7, a structural homolog of CD229's N-terminal Ig-variable domain, does not interact with CD229 or other SLAM family members, but mediates adhesion to monocyte-derived dendritic cells and attenuates production of TNF, IL-8, and IL-6 in DCs and myeloid cell lines, mimicking a function related to CD229 signaling. Anti-UL7 mAb generation, cell adhesion assays, cytokine production assays (ELISA), metalloproteinase inhibitor experiments, PMA stimulation Immunology and cell biology Low 21670740
2013 SLAMF3 (LY9) restoration in hepatocellular carcinoma (HCC) cell lines inhibits cell proliferation and migration, enhances apoptosis, and inhibits MAPK ERK1/2, JNK, and mTOR phosphorylation. SLAMF3 expression suppresses HCC xenograft progression in nude mice. SLAMF3 overexpression in HCC cell lines, proliferation and migration assays, apoptosis assay, Western blot for phospho-ERK/JNK/mTOR, xenograft mouse model PloS one Medium 24376606
2016 SLAMF3 overexpression in HCC cells retains RB in hypophosphorylated (active) form, which inactivates E2F transcription factor and represses PLK1 expression and activation, thereby inhibiting mitosis and tumor proliferation. SLAMF3 overexpression, Western blot for pRB/RB and PLK1, E2F reporter assay, cell cycle analysis, correlation in patient HCC samples Oncotarget Medium 26799423
2016 SLAMF3 overexpression in HCC cells specifically reduces MRP-1 (multidrug resistance protein 1) expression and function without affecting ABCG2 or MDR, thereby sensitizing cells to anti-cancer drugs. SLAMF3 overexpression, Western blot for MRP-1/ABCG2/MDR, drug efflux/cytotoxicity assays, correlation in patient HCC samples Oncotarget Medium 27081035

Source papers

Stage 0 corpus · 59 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP. Blood 100 11389028
2006 Ly9 (CD229)-deficient mice exhibit T cell defects yet do not share several phenotypic characteristics associated with SLAM- and SAP-deficient mice. Journal of immunology (Baltimore, Md. : 1950) 73 16365421
2005 CD229 (Ly9) lymphocyte cell surface receptor interacts homophilically through its N-terminal domain and relocalizes to the immunological synapse. Journal of immunology (Baltimore, Md. : 1950) 73 15905546
2004 Differential expression of SAP and EAT-2-binding leukocyte cell-surface molecules CD84, CD150 (SLAM), CD229 (Ly9) and CD244 (2B4). Tissue antigens 73 15245368
2020 CD229 CAR T cells eliminate multiple myeloma and tumor propagating cells without fratricide. Nature communications 67 32034142
2008 Association of LY9 in UK and Canadian SLE families. Genes and immunity 67 18216865
2011 Increased expression of SLAM receptors SLAMF3 and SLAMF6 in systemic lupus erythematosus T lymphocytes promotes Th17 differentiation. Journal of immunology (Baltimore, Md. : 1950) 59 22184727
2022 SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. Science immunology 57 35061505
2011 Surface molecule CD229 as a novel target for the diagnosis and treatment of multiple myeloma. Haematologica 57 21606160
2001 Molecular characterization and expression of a novel human leukocyte cell-surface marker homologous to mouse Ly-9. Blood 56 11369645
1992 Isolation and characterization of cDNA clones for mouse Ly-9. Journal of immunology (Baltimore, Md. : 1950) 52 1506686
2004 SAP increases FynT kinase activity and is required for phosphorylation of SLAM and Ly9. International immunology 51 15096483
2015 Utility of CD54, CD229, and CD319 for the identification of plasma cells in patients with clonal plasma cell diseases. Cytometry. Part B, Clinical cytometry 45 26130131
2011 Human cytomegalovirus UL7, a homologue of the SLAM-family receptor CD229, impairs cytokine production. Immunology and cell biology 42 21670740
2005 Identification of Grb2 as a novel binding partner of the signaling lymphocytic activation molecule-associated protein binding receptor CD229. Journal of immunology (Baltimore, Md. : 1950) 39 15879090
1995 Physical and genetic linkage of the genes encoding Ly-9 and CD48 on mouse and human chromosomes 1. Immunogenetics 34 7797269
2012 Cutting edge: Ly9 (CD229), a SLAM family receptor, negatively regulates the development of thymic innate memory-like CD8+ T and invariant NKT cells. Journal of immunology (Baltimore, Md. : 1950) 33 23225888
1996 Isolation and characterization of cDNA clones for Humly9: the human homologue of mouse Ly9. Immunogenetics 33 8537117
1980 A monoclonal antibody detecting the Ly-9.2 (Lgp 100) cell-membrane alloantigen. Immunogenetics 33 6160098
2016 Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus. Proceedings of the National Academy of Sciences of the United States of America 32 27482100
2015 CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma. Human vaccines & immunotherapeutics 32 26001047
2013 Ly9 (CD229) Cell-Surface Receptor is Crucial for the Development of Spontaneous Autoantibody Production to Nuclear Antigens. Frontiers in immunology 30 23914190
2013 Systemic lupus erythematosus immune complexes increase the expression of SLAM family members CD319 (CRACC) and CD229 (LY-9) on plasmacytoid dendritic cells and CD319 on CD56(dim) NK cells. Journal of immunology (Baltimore, Md. : 1950) 30 23956418
2023 Systematic single amino acid affinity tuning of CD229 CAR T cells retains efficacy against multiple myeloma and eliminates on-target off-tumor toxicity. Science translational medicine 29 37467316
2003 The cell surface expression of SAP-binding receptor CD229 is regulated via its interaction with clathrin-associated adaptor complex 2 (AP-2). The Journal of biological chemistry 26 12621057
2019 Upregulation of SLAMF3 on human T cells is induced by palmitic acid through the STAT5-PI3K/Akt pathway and features the chronic inflammatory profiles of type 2 diabetes. Cell death & disease 25 31332162
2002 Mouse novel Ly9: a new member of the expanding CD150 (SLAM) family of leukocyte cell-surface receptors. Immunogenetics 25 12242590
2012 CD3-T cell receptor co-stimulation through SLAMF3 and SLAMF6 receptors enhances RORγt recruitment to the IL17A promoter in human T lymphocytes. The Journal of biological chemistry 23 22989874
2013 Identification of SLAMF3 (CD229) as an inhibitor of hepatocellular carcinoma cell proliferation and tumour progression. PloS one 20 24376606
2007 Characterization of mouse CD229 (Ly9), a leukocyte cell surface molecule of the CD150 (SLAM) family. Tissue antigens 19 17919264
2022 CD229 (Ly9) a Novel Biomarker for B-Cell Malignancies and Multiple Myeloma. Cancers 18 35565280
2020 SLAMF3-Mediated Signaling via ERK Pathway Activation Promotes Aggressive Phenotypic Behaviors in Multiple Myeloma. Molecular cancer research : MCR 18 31974290
2016 Hepatocyte SLAMF3 reduced specifically the multidrugs resistance protein MRP-1 and increases HCC cells sensitization to anti-cancer drugs. Oncotarget 17 27081035
2015 Targeting of Ly9 (CD229) Disrupts Marginal Zone and B1 B Cell Homeostasis and Antibody Responses. Journal of immunology (Baltimore, Md. : 1950) 17 26667173
2000 Gene structure of the mouse leukocyte cell surface molecule Ly9. Immunogenetics 17 10970093
2018 Evaluation of CD229 as a new alternative plasma cell gating marker in the flow cytometric immunophenotyping of monoclonal gammopathies. Cytometry. Part B, Clinical cytometry 16 29316178
2006 Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells. Experimental hematology 16 16797413
2015 A polymorphism in a phosphotyrosine signalling motif of CD229 (Ly9, SLAMF3) alters SH2 domain binding and T-cell activation. Immunology 15 26221972
2018 The role of surface molecule CD229 in Multiple Myeloma. Clinical immunology (Orlando, Fla.) 14 30326256
2011 Extracellular production of beta-amylase by a halophilic isolate, Halobacillus sp. LY9. Journal of industrial microbiology & biotechnology 14 21505914
2016 RB/PLK1-dependent induced pathway by SLAMF3 expression inhibits mitosis and control hepatocarcinoma cell proliferation. Oncotarget 13 26799423
2022 Rescuing SLAMF3 Expression Restores Sorafenib Response in Hepatocellular Carcinoma Cells through the Induction of Mesenchymal-to-Epithelial Transition. Cancers 12 35205659
2018 Ly9 (CD229) Antibody Targeting Depletes Marginal Zone and Germinal Center B Cells in Lymphoid Tissues and Reduces Salivary Gland Inflammation in a Mouse Model of Sjögren's Syndrome. Frontiers in immunology 11 30519241
2017 Ly9 (SLAMF3) receptor differentially regulates iNKT cell development and activation in mice. European journal of immunology 11 28980301
2019 Viral CD229 (Ly9) homologs as new manipulators of host immunity. Journal of leukocyte biology 9 30791129
2024 A review: Mechanisms and molecular pathways of signaling lymphocytic activation molecule family 3 (SLAMF3) in immune modulation and therapeutic prospects. International immunopharmacology 8 38626547
2023 SLAMF3 promotes Th17 differentiation and is reversed by iguratimod through JAK1/STAT3 pathway in primary Sjögren's syndrome. International immunopharmacology 8 38061117
2022 Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade. British journal of cancer 8 35618786
2019 The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease. Frontiers in immunology 8 31057553
2014 The expression of the hepatocyte SLAMF3 (CD229) receptor enhances the hepatitis C virus infection. PloS one 6 24927415
2025 Human LY9 governs CD4+ T cell IFN-γ immunity to Mycobacterium tuberculosis. Science immunology 4 40446017
2022 Utility of CD229 as novel marker in measurable residual disease assessment in multiple myeloma-An evidence-based approach. International journal of laboratory hematology 4 36403963
2022 CD229 interacts with RASAL3 to activate RAS/ERK pathway in multiple myeloma proliferation. Aging 4 36445333
2020 The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma. Experimental hematology 4 32818503
2025 RUNX1/SLAMF3 Axis Drives Immunosuppression to Contribute to Colorectal Cancer Liver Metastasis by Blocking Phagocytosis and Depleting C1QC+ Tumor-Associated Macrophages. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40448626
2023 Combination of CD49b and CD229 Reveals a Subset of Multipotent Progenitors With Short-Term Activity Within the Hematopoietic Stem Cell Compartment. Stem cells translational medicine 3 37706539
2025 Bicistronic CAR T Cell against BCMA and CD229 Effectively Controls Myeloma Even When BCMA Expression Is Limited. Cancer immunology research 2 40576564
2023 Transcriptomic analysis of B cells suggests that CD70 and LY9 may be novel features in patients with systemic lupus erythematosus. Heliyon 2 37144201
2025 Proteome-wide mendelian randomization identifies FCRL3 and LY9 as potential therapeutic targets for lymphoma. Discover oncology 0 41222800