Affinage

CD84

SLAM family member 5 · UniProt Q9UIB8

Length
345 aa
Mass
38.8 kDa
Annotated
2026-04-28
49 papers in source corpus 26 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD84 (SLAMF5) is a homophilic cell-surface receptor of the SLAM/CD2 immunoglobulin superfamily that functions as a context-dependent signaling hub orchestrating intercellular adhesion, immune activation, immune suppression, and metabolic regulation across hematopoietic lineages. Its N-terminal Ig-V domain forms an orthogonal homodimer with submicromolar affinity, enabling homophilic trans-interactions that sustain T cell–B cell contacts required for germinal center formation and that bridge CLL or AML cells to their supportive microenvironment (PMID:17563375, PMID:20153220, PMID:27452524). Upon engagement, cytoplasmic ITSM tyrosines are phosphorylated by Src-family kinases (Lck), Fes, or BTK, recruiting SAP or EAT-2 to activate MAPK, NF-κB, Akt/NRF2, and Vav-1 pathways, or alternatively recruiting SHP-1/Dok-1 to inhibit mast-cell degranulation and dampen Syk–LAT–PLCγ1 signaling (PMID:12928397, PMID:22068234, PMID:20628063, PMID:39110779, PMID:40198133). CD84 homophilic interactions also drive PD-L1 upregulation that suppresses T cell function in CLL and myeloma microenvironments, promote MDSC differentiation, regulate NHEJ DNA repair in AML through SAP–AKT signaling, and mediate platelet–T cell crosstalk in cerebral thrombo-inflammation, while its surface levels are controlled by ADAM10 ectodomain shedding and calpain-mediated intracellular cleavage (PMID:30277471, PMID:33465053, PMID:40633676, PMID:32762491, PMID:23025437).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1997 High

    Identification of CD84 as a new Ig-superfamily member on hematopoietic cells established the molecular identity and expression pattern of the receptor, enabling subsequent functional studies.

    Evidence cDNA cloning, Northern blot, and flow cytometry with mAbs on human hematopoietic cells

    PMID:9310491

    Open questions at the time
    • No ligand or signaling function defined
    • Expression on non-hematopoietic tissues not examined
  2. 2001 High

    Demonstration that CD84 is a homophilic receptor whose first Ig-like domain mediates self-binding, and that ligation costimulates IFN-γ production, established both the binding mode and a functional consequence of engagement.

    Evidence Soluble CD84-Ig fusion binding assays, domain chimeras, and T cell costimulation assays with anti-CD84 mAbs

    PMID:11564780

    Open questions at the time
    • Structural basis of homophilic interaction unknown
    • Downstream signaling pathway not mapped
  3. 2001 High

    Discovery that SAP binds phosphorylated CD84 cytoplasmic tyrosines connected CD84 to the SAP-dependent signaling network disrupted in X-linked lymphoproliferative disease.

    Evidence Yeast two-hybrid, COS cell transfection, and biochemical binding assays in lymphoid cells

    PMID:11389028

    Open questions at the time
    • Specific phosphotyrosine residues not mapped
    • In vivo relevance of SAP recruitment to CD84 not tested
  4. 2002 Medium

    Showing that CD84 is rapidly phosphorylated on primary B cells and recruits both SAP and EAT-2 expanded the adaptor repertoire and implicated CD84 in memory B cell signaling.

    Evidence Anti-CD84 ligation, immunoprecipitation, and Western blot in primary human B cells

    PMID:12115647

    Open questions at the time
    • EAT-2 binding site on CD84 not mapped
    • Functional consequence in B cell differentiation not shown
  5. 2003 High

    Mapping the critical phosphotyrosine Y262 for SAP binding and identifying Lck as the upstream kinase defined the proximal signaling mechanism; use of SAP-deficient XLP patient cells revealed SAP-independent costimulatory pathways.

    Evidence Site-directed mutagenesis, Lck inhibition, and T cell proliferation assays including XLP patient cells

    PMID:12928397

    Open questions at the time
    • SAP-independent pathway components not identified
    • Role of other Src-family kinases not excluded
  6. 2007 High

    The 2.0 Å crystal structure of the CD84 Ig-V domain revealed the orthogonal homodimer geometry and submicromolar self-association affinity, explaining specificity among SLAM family members and compatibility with immunological synapse dimensions.

    Evidence X-ray crystallography and analytical ultracentrifugation

    PMID:17563375

    Open questions at the time
    • Full-length extracellular structure not solved
    • Dynamics of dimer at the cell surface not characterized
  7. 2008 High

    CD84 was shown to function as an inhibitory receptor in mast cells via Y279/Y324-dependent recruitment of Dok-1 and c-Cbl, dampening MAP kinase signaling—demonstrating that CD84 can switch between activating and inhibitory outputs depending on cellular context.

    Evidence Tyrosine mutants in RBL-2H3 cells, degranulation assays, and signaling Western blots

    PMID:18243321

    Open questions at the time
    • Direct interaction between CD84 and Dok-1/c-Cbl not shown by co-IP
    • Physiological ligand engagement in mast cells not addressed
  8. 2010 High

    Genetic deletion of CD84 in mice proved it is required for sustained T:B cell contact and germinal center formation, and separately, CD84 modulates macrophage TLR4 responses via its second ITSM (Y300), activating MAPK/NF-κB—establishing dual in vivo roles in adaptive and innate immunity.

    Evidence CD84-knockout mice with intravital imaging, GC analysis, and macrophage gain/loss-of-function with ITSM mutants

    PMID:20153220 PMID:20628063

    Open questions at the time
    • Relative contribution of CD84 versus Ly108 to GC formation not fully dissected
    • Downstream transcriptional targets of NF-κB in macrophages not defined
  9. 2010 High

    EAT-2 adaptors were shown to positively regulate CD84-dependent NK cell cytotoxicity through Vav-1 phosphorylation, extending CD84's functional repertoire to innate cytotoxicity.

    Evidence EAT-2A/B-deficient mice, NK killing assays, Vav-1 phosphorylation Western blot

    PMID:20962259

    Open questions at the time
    • Direct EAT-2–Vav-1 interaction downstream of CD84 not shown
    • Contribution of CD84 versus CD244 not individually dissected
  10. 2011 High

    In SAP/EAT-2-negative human mast cells, identification of Fes as the kinase phosphorylating CD84 and SHP-1 as the effector phosphatase revealed the molecular logic of CD84's inhibitory mode, explaining context-dependent signaling switching.

    Evidence FcεRI/CD84 co-cross-linking in LAD2 and primary mast cells, calcium flux, and phospho-signaling analysis

    PMID:22068234

    Open questions at the time
    • Direct Fes–CD84 physical interaction not demonstrated
    • Relative roles of SHP-1 versus SHP-2 not fully resolved
  11. 2012 High

    Identification of ADAM10 and calpain as the sheddase and intracellular protease regulating CD84 surface levels on platelets established a post-translational control mechanism for receptor availability.

    Evidence ADAM10-, ADAM17-deficient, and calpain-inhibited mouse platelets with shedding assays

    PMID:23025437

    Open questions at the time
    • Cleavage sites not mapped at amino-acid resolution
    • Functional consequence of soluble CD84 ectodomain from platelets not tested
  12. 2013 High

    Discovery that MIF/CD74 induces CD84 expression on CLL cells, whose homophilic engagement sustains survival via Bcl-2/Mcl-1, established CD84 as a druggable pro-survival factor in CLL.

    Evidence CD84 knockdown/blocking antibodies in CLL cells in vitro and in vivo, Bcl-2/Mcl-1 Western blot

    PMID:23435417

    Open questions at the time
    • Signaling intermediates between CD84 and Bcl-2/Mcl-1 not defined
    • Patient genetic heterogeneity effects not examined
  13. 2015 High

    Lupus-associated CD84 alleles on GC B cells break tolerance, and triple SLAM-family knockouts show enhanced antibody responses, positioning CD84 as both a positive regulator of GC tolerance and a negative regulator of humoral output.

    Evidence BAC-transgenic rescue on autoimmune background, single/triple SLAMF1/5/6 KO mice, adoptive transfers

    PMID:25801429 PMID:25926831

    Open questions at the time
    • Molecular basis of allelic functional differences in CD84 not defined
    • Individual contribution of CD84 versus SLAMF6 in triple KO not separable
  14. 2016 High

    CD84 was shown to bridge CLL cells to stromal cells through homophilic trans-interaction, with blocking antibodies disrupting this bridge and inducing death in vivo, validating the therapeutic concept.

    Evidence Co-culture, blocking antibodies in vitro and in mouse CLL models

    PMID:27452524

    Open questions at the time
    • Downstream signaling in stromal cells not characterized
    • Resistance mechanisms to CD84 blockade not explored
  15. 2018 High

    CD84 homophilic engagement was found to upregulate PD-L1 on CLL cells and PD-1 on T cells, connecting CD84 to immune checkpoint regulation and explaining microenvironmental T cell exhaustion.

    Evidence Human and mouse CD84-mediated cell interaction assays, flow cytometry for PD-L1/PD-1, T cell functional assays

    PMID:30277471

    Open questions at the time
    • Signaling intermediates from CD84 to PD-L1 transcription not identified
    • Synergy with anti-PD-1 therapy not tested
  16. 2020 High

    Cell-type-specific CD84 knockouts demonstrated that platelet-derived soluble CD84 drives CD4+ T cell motility and cerebral infiltration after ischemic stroke, extending CD84 function beyond classical immunity to thrombo-inflammation.

    Evidence Platelet- and T cell-specific CD84 KO mice, experimental stroke models, in vitro T cell motility assays, human patient arterial blood analysis

    PMID:32762491

    Open questions at the time
    • Receptor on T cells mediating response to soluble CD84 assumed to be CD84 but not formally excluded to be another receptor
    • Downstream T cell signaling pathway not mapped
  17. 2021 High

    MIF-induced CD84 on microenvironmental cells was shown to drive MDSC differentiation and PD-L1 upregulation in myeloma, suppressing T cell function—generalizing the CD84–PD-L1 axis beyond CLL.

    Evidence Co-culture, CD84 knockdown/blocking, flow cytometry, in vivo myeloma models

    PMID:33465053

    Open questions at the time
    • Signaling from CD84 to MDSC differentiation transcription factors not fully defined
    • Role in solid tumors beyond breast not explored
  18. 2024 High

    Identification of CD84 as a BTK substrate placed it within alcohol-induced neutrophil inflammatory signaling; separately, CD84 was linked to β-catenin/Tcf4-driven IL-10 transcription in Bregs and to IKZF1–SHP2-mediated TAM polarization in glioma, revealing new lineage-specific downstream pathways.

    Evidence LC-MS/MS kinase substrate identification, myeloid Btk KO mice, ChIP/promoter binding for β-catenin/Tcf4, GSC-TAM co-culture with knockdown

    PMID:39110779 PMID:39112517 PMID:39466774

    Open questions at the time
    • BTK phosphorylation site(s) on CD84 not mapped
    • β-catenin activation mechanism downstream of CD84 not defined
    • SHP2 role in glioma context from single study
  19. 2025 High

    CD84 was shown to regulate AML cell metabolism (oxidative phosphorylation, fatty acid oxidation) via Akt/NRF2, NHEJ DNA repair via SAP–AKT–PRKDC/LIG4 upregulation, and myeloid cell activation in EAE via BHLHE40/CD52—demonstrating broad cell-intrinsic roles in metabolic fitness, genomic stability, and neuroinflammation.

    Evidence CD84 KD/OE in AML cells, PDX and mouse leukemia models, electron microscopy, metabolic flux assays, NHEJ reporter, conditional myeloid KO in EAE, pharmacological blockade, human iPSC-derived microglia

    PMID:40198133 PMID:40633676 PMID:40920820

    Open questions at the time
    • How CD84 surface engagement is transduced to mitochondrial dynamics is unknown
    • Whether NHEJ regulation is SAP-dependent in primary AML patient cells not confirmed
    • BHLHE40 regulation by CD84 signaling intermediates not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD84 switches between activating (SAP/EAT-2-dependent) and inhibitory (SHP-1/Dok-1-dependent) signaling modes in different cell types remains mechanistically undefined; the structural basis for adaptor selectivity at ITSM motifs and the identity of SAP-independent costimulatory pathways are open questions.
  • No structural model of CD84 cytoplasmic domain with adaptors
  • SAP-independent costimulatory pathway components unidentified
  • Context-dependent adaptor selection mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098631 cell adhesion mediator activity 4 GO:0098772 molecular function regulator activity 4
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 9 R-HSA-162582 Signal Transduction 7 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1430728 Metabolism 1 R-HSA-73894 DNA Repair 1
Partners
BTKDOK1FESLCKPTPN11PTPN6SH2D1ASH2D1B

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CD84 was identified as a novel member of the Ig superfamily with two extracellular Ig-like domains, a transmembrane region, and an 83-amino acid cytoplasmic domain, encoded by a gene mapping to chromosome 1q24, and expressed predominantly on hematopoietic cells including B lymphocytes and monocytes. cDNA cloning, Northern blot, flow cytometry with monoclonal antibodies Blood High 9310491
2001 CD84 functions as a homophilic adhesion molecule: a soluble CD84-Ig fusion protein binds specifically to CD84-transfected cells but not to cells expressing other CD2-subfamily receptors, and this interaction is mediated exclusively by the first extracellular Ig-like domain and is independent of the cytoplasmic tail. CD84-Ig soluble fusion protein binding assays, domain chimera analysis, anti-CD84 mAb blocking Journal of immunology High 11564780
2001 CD84 co-stimulates IFN-γ secretion in human lymphocytes when co-ligated with CD3, demonstrating a costimulatory function. In vitro stimulation assay with anti-CD84 mAbs or CD84-Ig fusion protein plus anti-CD3 Journal of immunology Medium 11564780
2001 The cytoplasmic tails of CD84 and Ly-9 recruit SAP (SH2D1A) via specific tyrosine residues; this interaction is most efficient when those tyrosines are phosphorylated, placing CD84 in the SAP-dependent signaling network disrupted in X-linked lymphoproliferative disease. Yeast two-hybrid, COS cell transfections, biochemical binding assays in lymphoid cells Blood High 11389028
2002 CD84 is rapidly tyrosine-phosphorylated upon antibody-mediated ligation on primary human B cells and recruits both SAP and EAT-2 via its cytoplasmic tail, suggesting a signaling role in memory B cell activation. Anti-CD84 mAb ligation, immunoprecipitation, Western blot for tyrosine phosphorylation and SAP/EAT-2 recruitment European journal of immunology Medium 12115647
2003 CD84 is tyrosine-phosphorylated on activated T cells via the Src kinase Lck; phosphorylation at Y262 in the cytoplasmic domain is required for SAP recruitment, which also requires R32 in the SAP SH2 domain. CD84 ligation enhances anti-CD3-stimulated T cell proliferation via both SAP-dependent and SAP-independent mechanisms. Site-directed mutagenesis of CD84 cytoplasmic domain and SAP SH2 domain, Lck inhibition, T cell proliferation assays with XLP patient (SAP-deficient) T cells Journal of immunology High 12928397
2007 Crystal structure of the human CD84 immunoglobulin variable domain at 2.0 Å resolution reveals an orthogonal homophilic dimer similar to NTB-A. Solution studies show CD84 self-associates with a Kd in the submicromolar range. Structural differences at homophilic interfaces prevent undesired heterodimer formation among SLAM family members, and the ~140 Å end-to-end dimension allows colocalization within the immunological synapse. X-ray crystallography (2.0 Å), analytical ultracentrifugation for Kd measurement Proceedings of the National Academy of Sciences of the United States of America High 17563375
2008 CD84 inhibits FcεRI-mediated mast cell degranulation through homophilic interaction; this inhibitory mechanism is independent of SAP and SHP-2 recruitment but requires tyrosines Y279 and Y324 in the CD84 cytoplasmic domain, and is associated with increased phosphorylation of Dok-1 and c-Cbl and impaired MAP kinase (ERK1/2, JNK, p38) phosphorylation. CD84 transfection in RBL-2H3 cells, tyrosine mutants (Y279F, ΔY324), degranulation assays, Western blot for signaling intermediates Molecular immunology High 18243321
2010 The SLAM family member CD84 is required for prolonged T cell:B cell contact, optimal T follicular helper function, and germinal center formation in vivo. T cell:B cell interactions have both an early integrin-dependent phase and a sustained SAP-dependent phase requiring CD84 and Ly108. CD84-deficient mice, intravital two-photon microscopy, in vitro T:B adhesion assays, in vivo germinal center analysis Immunity High 20153220
2010 In mouse macrophages, CD84 modulates TLR4 downstream signaling: transfection of CD84 in RAW-264.7 cells increases MAPK phosphorylation and NF-κB activation upon LPS stimulation, elevates TNF-α and MCP-1, and reduces IL-10 and IL-6 production. This modulatory effect is mediated specifically by Y300 within the second ITSM of CD84. CD84 transfection and knockdown in RAW-264.7 macrophages and bone-marrow-derived macrophages, ITSM tyrosine mutant (Y300), MAPK/NF-κB reporter assays, cytokine ELISA Journal of leukocyte biology High 20628063
2010 EAT-2A and EAT-2B adapters positively regulate CD84- and CD244-dependent NK cell killing of tumor cells in C57BL/6 mice and mediate phosphorylation of Vav-1 downstream of these SLAM family receptors. EAT-2A/B-deficient mice (C57BL/6 background), NK cytotoxicity assays, Vav-1 phosphorylation by Western blot Journal of immunology High 20962259
2011 In human mast cells, which lack SAP and EAT-2, CD84 is tyrosine-phosphorylated upon FcεRI engagement and inhibits FcεRI-mediated degranulation and cytokine release. Inhibition is mediated by the Fes kinase (which phosphorylates the CD84 inhibitory motif) and by increased SHP-1 phosphorylation, and is accompanied by dampened calcium mobilization and reduced Syk-LAT-PLCγ1 axis activity. FcεRI/CD84 co-cross-linking in LAD2 cells and primary human CD34+-derived mast cells, calcium flux assay, Western blot for Syk, LAT, PLCγ1, Fes, SHP-1 phosphorylation Journal of immunology High 22068234
2012 CD84 is shed from platelets by ADAM10-mediated ectodomain cleavage and simultaneously cleaved intracellularly by calpain. ADAM10 is the principal sheddase (ADAM17 is dispensable), and CD84 is constitutively shed in vivo. Biochemical shedding assays in human and murine platelets, ADAM10-deficient, ADAM17-deficient, and calpain-inhibited/deficient mouse models, Western blot Journal of thrombosis and haemostasis High 23025437
2013 CD84 expression in CLL cells is regulated by macrophage migration inhibitory factor (MIF) via its receptor CD74. Activation of surface CD84 initiates a signaling cascade that enhances CLL cell survival; downmodulation or immune-mediated blockade of CD84 induces cell death in vitro and in vivo, with concomitant reduction of Bcl-2 and Mcl-1 expression. CD84 knockdown and blocking antibodies in CLL cells in vitro and in vivo mouse models, Western blot for Bcl-2/Mcl-1, analysis of clinical trial samples (milatuzumab treatment) Oncogene High 23435417
2015 B cell-intrinsic CD84 and Ly108 maintain germinal center B cell tolerance; lupus-associated alleles of CD84 and Ly108 on GC B cells are sufficient to break tolerance and increase autoantibody production, and B6.Sle1b B cells have reduced B cell-T cell conjugate formation reversed by B6 CD84/Ly108 alleles. BAC-transgenic mice overexpressing B6 alleles of CD84/Ly108 on autoimmune-prone background, GC response measurement, B cell-T cell conjugate assays, BCR signaling assays Journal of immunology High 25801429
2015 SLAMF1, SLAMF5 (CD84), and SLAMF6 act as negative regulators of humoral immunity; triple-knockout mice show ~2-fold higher T-dependent and T-independent antibody responses. B cell-intrinsic activity accounts for the predominant effect, and anti-SLAMF6 antibody treatment inhibits Tfh and GC B cell development. Single and triple Slamf1/5/6 knockout mice, adoptive co-transfer assays, anti-SLAMF6 antibody treatment, antibody titer measurement Frontiers in immunology High 25926831
2016 CD84 bridges CLL cells and stromal microenvironment cells through homophilic self-association; CD84 expressed on CLL cells interacts with CD84 on stromal cells inducing survival signaling in both cell types. Blocking CD84 in vitro and in vivo disrupts this interaction and induces cell death. Co-culture assays, CD84 blocking antibodies in vitro and in vivo mouse models, cell survival/death assays Oncogene High 27452524
2016 CRISPR-mediated triple knockout of SLAMF1, SLAMF5, and SLAMF6 worsens defects in iNKT cell development seen in SLAMF6 single-knockout mice, supporting positive signaling roles for these receptors in iNKT development, with potential redundancy among them. Cas9/CRISPR triple-knockout mice, flow cytometric analysis of iNKT and conventional lymphocyte populations, germinal center analysis PloS one Medium 27258160
2018 Cell-cell interaction mediated through CD84 upregulates PD-L1 expression on CLL cells and their microenvironment, and PD-1 expression on T cells, resulting in suppression of T cell function in vitro and in vivo. This identifies CD84 as a regulator of PD-1/PD-L1 immune checkpoints in CLL. Human and mouse CD84-mediated cell-cell interaction assays, PD-L1/PD-1 expression by flow cytometry, T cell functional assays in vitro and in vivo The Journal of clinical investigation High 30277471
2020 CD84 mediates cerebral thrombo-inflammation in ischemic stroke: platelet-derived soluble CD84 enhances motility of CD4+ T cells through homophilic CD84 interaction. Mice lacking CD84 on either platelets or T cells show reduced cerebral CD4+ T cell infiltration and thrombotic activity after experimental stroke. CD84-deficient mice (cell-type specific), experimental stroke models, in vitro T cell motility assays with soluble CD84, clinical analysis of arterial blood from ischemic patients Circulation research High 32762491
2021 In multiple myeloma, myeloma cells secrete MIF which induces CD84 expression on microenvironmental cells. CD84 activation on these cells upregulates genes regulating M-MDSC and G-MDSC differentiation and increases PD-L1 expression on MDSCs, suppressing T cell function. Downregulation or blocking of CD84 reduces MDSC accumulation and elevates T cell activity. In vitro co-culture, CD84 knockdown and blocking antibodies, flow cytometry for MDSC markers and PD-L1, in vivo tumor models JCI insight High 33465053
2024 CD84 is a kinase substrate of BTK (identified by liquid chromatography-tandem mass spectrometry); CD84 promotes alcohol-induced IL-1β and TNF-α in primary human neutrophils, an effect inhibited by CD84-blocking antibody, placing CD84 downstream of BTK in alcohol-induced granulopoiesis and neutrophil inflammation. LC-MS/MS kinase substrate identification, BTK inhibitor treatment, myeloid-specific Btk knockout mice, CD84-blocking antibody in vitro Science translational medicine High 39110779
2024 In TNBC, CD84 activates a Breg cascade involving β-catenin and Tcf4, which drive transcription of IL-10 by binding to its promoter and the promoter of its regulator AhR, leading to Breg expansion and suppression of other immune cells. In vitro CD84 stimulation, ChIP/promoter binding assays for β-catenin/Tcf4, IL-10 reporter, Breg expansion assays, in vivo tumor models Cell reports Medium 39466774
2024 In glioma, CCL2 from mesenchymal glioma stem cells induces IKZF1 expression in tumor-associated macrophages, which promotes M2 polarization via the CD84-SHP2 pathway. GSC-TAM co-culture, bioinformatics, knockdown experiments, determination of TAM polarization phenotypes Oncogene Medium 39112517
2025 In AML, CD84 regulates energy metabolism and mitochondrial dynamics; CD84 depletion alters mitochondrial ultrastructure, reduces oxidative phosphorylation and fatty acid oxidation, blocks Akt phosphorylation, and downmodulates NRF2, impairing antioxidant defense. Conversely, CD84 overexpression stabilizes NRF2 and promotes its transcriptional activation. CD84 knockdown and overexpression in AML cell lines and patient-derived xenografts, MLL-AF9 and inv(16) mouse models, electron microscopy for mitochondrial ultrastructure, metabolic flux assays, Western blot for Akt/NRF2 The Journal of clinical investigation High 40198133
2025 In AML, CD84 promotes expression of NHEJ DNA repair core factors (PRKDC, LIG4, XRCC5, DCLRE1C) by recruiting SAP and activating the AKT signaling pathway; CD84 knockdown inhibits NHEJ repair, causing double-strand break accumulation and apoptosis. CD84 knockdown in AML cells, SAP co-immunoprecipitation, AKT phosphorylation Western blot, NHEJ reporter assays, γH2AX foci (DSB accumulation), in vivo xenograft models Molecules and cells Medium 40633676
2025 SLAMF5/CD84 deficiency in myeloid cells (microglia and border-associated macrophages) reduces expression of activation and costimulatory molecules MHC II and CD80, delays EAE onset and progression. This is mediated at least in part through the transcription factor BHLHE40 and its regulation of CD52. Pharmacological blockade of SLAMF5 in the brain halts disease progression. Total and brain-specific SLAMF5-deficient mice, EAE model, flow cytometry for activation markers, BHLHE40/CD52 mechanistic analysis, pharmacological blockade, human iPSC-derived microglia PLoS biology High 40920820

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 316 20153220
2001 CD84 functions as a homophilic adhesion molecule and enhances IFN-gamma secretion: adhesion is mediated by Ig-like domain 1. Journal of immunology (Baltimore, Md. : 1950) 113 11564780
2001 Cell surface receptors Ly-9 and CD84 recruit the X-linked lymphoproliferative disease gene product SAP. Blood 100 11389028
1997 CD84 leukocyte antigen is a new member of the Ig superfamily. Blood 77 9310491
2020 CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-Inflammation in Acute Stroke. Circulation research 74 32762491
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
2002 CD84 is up-regulated on a major population of human memory B cells and recruits the SH2 domain containing proteins SAP and EAT-2. European journal of immunology 73 12115647
2007 Structure of CD84 provides insight into SLAM family function. Proceedings of the National Academy of Sciences of the United States of America 64 17563375
2021 CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma. JCI insight 62 33465053
2021 The survival and function of IL-10-producing regulatory B cells are negatively controlled by SLAMF5. Nature communications 59 33767202
2018 CD84 regulates PD-1/PD-L1 expression and function in chronic lymphocytic leukemia. The Journal of clinical investigation 57 30277471
2003 Functional requirements for interactions between CD84 and Src homology 2 domain-containing proteins and their contribution to human T cell activation. Journal of immunology (Baltimore, Md. : 1950) 54 12928397
2017 Polymorphisms in CD84, IL12B and TNFAIP3 are associated with response to biologics in patients with psoriasis. The British journal of dermatology 46 27564082
2018 CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and autoimmune disorders. Clinical immunology (Orlando, Fla.) 45 30522694
2010 Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-induced cytokine secretion by macrophages. Journal of leukocyte biology 44 20628063
2013 CD84 is a survival receptor for CLL cells. Oncogene 40 23435417
2015 Negative Regulation of Humoral Immunity Due to Interplay between the SLAMF1, SLAMF5, and SLAMF6 Receptors. Frontiers in immunology 37 25926831
2015 B cell-intrinsic CD84 and Ly108 maintain germinal center B cell tolerance. Journal of immunology (Baltimore, Md. : 1950) 33 25801429
2003 CD84 expression on human hematopoietic progenitor cells. Experimental hematology 33 12962726
2001 Genetic approach to insight into the immunobiology of human dendritic cells and identification of CD84-H1, a novel CD84 homologue. Clinical cancer research : an official journal of the American Association for Cancer Research 33 11300479
2010 Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse. Journal of immunology (Baltimore, Md. : 1950) 32 20962259
2016 CD84 mediates CLL-microenvironment interactions. Oncogene 28 27452524
2021 Circ-Usp10 promotes microglial activation and induces neuronal death by targeting miRNA-152-5p/CD84. Bioengineered 26 34753388
2024 Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors. Cell reports. Medicine 25 38242120
2011 CD84 negatively regulates IgE high-affinity receptor signaling in human mast cells. Journal of immunology (Baltimore, Md. : 1950) 24 22068234
2012 The SLAM family member CD84 is regulated by ADAM10 and calpain in platelets. Journal of thrombosis and haemostasis : JTH 20 23025437
2000 Characterization of MAX.3 antigen, a glycoprotein expressed on mature macrophages, dendritic cells and blood platelets: identity with CD84. The Biochemical journal 20 10698700
1999 Molecular cloning, characterization, and chromosomal localization of the mouse homologue of CD84, a member of the CD2 family of cell surface molecules. Immunogenetics 19 10079287
2008 The leukocyte receptor CD84 inhibits Fc epsilon RI-mediated signaling through homophilic interaction in transfected RBL-2H3 cells. Molecular immunology 18 18243321
2018 Elucidating the Role of CD84 and AHR in Modulation of LPS-Induced Cytokines Production by Cruciferous Vegetable-Derived Compounds Indole-3-Carbinol and 3,3'-Diindolylmethane. International journal of molecular sciences 17 29364159
2016 CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports Positive Signaling Roles in NKT Cell Development. PloS one 17 27258160
2014 Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis. PloS one 14 25551754
2022 CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis. Microbiology spectrum 13 35196822
2024 CCL2 mediated IKZF1 expression promotes M2 polarization of glioma-associated macrophages through CD84-SHP2 pathway. Oncogene 12 39112517
2024 CD84 as a therapeutic target for breaking immune tolerance in triple-negative breast cancer. Cell reports 12 39466774
2014 CD84 is markedly up-regulated in Kawasaki disease arteriopathy. Clinical and experimental immunology 12 24635044
2000 Genomic characterization of CD84 reveals the existence of five isoforms differing in their cytoplasmic domains. Tissue antigens 12 10746783
2024 Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors. Nature communications 6 39003273
2024 In vivo Bruton's tyrosine kinase inhibition attenuates alcohol-associated liver disease by regulating CD84-mediated granulopoiesis. Science translational medicine 6 39110779
2019 Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner. Oncogene 6 31772329
2025 Identification of CD84 as a potent survival factor in acute myeloid leukemia. The Journal of clinical investigation 5 40198133
2025 Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors. Computer methods and programs in biomedicine 3 39847992
2025 Tumor-derived CD84 promotes growth of acute myeloid leukemia cells via regulating nonhomologous DNA end-joining pathway. Molecules and cells 1 40633676
2026 Influenza virus infection drives upregulation of CD84 across a broad range of immune cells. Clinical & translational immunology 0 41816098
2026 Integrated Multi-Omics Profiling Identifies CD84-Associated Microglial Alterations in Focal Cortical Dysplasia Type II. Journal of inflammation research 0 41859381
2025 A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias. Leukemia 0 40770072
2025 Exploring SLAMF5/CD84 in Cancer: Advancing the Frontiers of Tumor Immunology. Cell biology international 0 40847794
2025 The immune receptor SLAMF5 regulates myeloid-cell mediated neuroinflammation in multiple sclerosis. PLoS biology 0 40920820
2025 Myeloid-Derived Suppressor Cells for Achieving Transplant Tolerance: Preclinical Testing of CD84+/MerTK+ Myeloid-Derived Suppressor Cells to Control Alloreactivity. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 0 41255114