Affinage

CD84

SLAM family member 5 · UniProt Q9UIB8

Length
345 aa
Mass
38.8 kDa
Annotated
2026-06-09
51 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD84 (SLAMF5) is a self-ligand homophilic cell-surface adhesion receptor of the SLAM immunoreceptor family that converts cell-cell contact into intracellular signaling to regulate immune cell interactions, survival, and effector function (PMID:11564780, PMID:17563375). Homophilic recognition is mediated exclusively by the membrane-distal Ig-like domain 1, which forms a submicromolar orthogonal dimer whose interface chemistry discriminates CD84 from other SLAM family members to prevent heterodimerization (PMID:11564780, PMID:17563375). Engagement triggers Lck-dependent tyrosine phosphorylation of cytoplasmic ITSM motifs, which then function as a phospho-tyrosine switch: phosphorylated Y262 recruits the adaptors SAP and EAT-2 as positive signaling mediators, while in other cell contexts the receptor instead engages the inhibitory kinase Fes and the phosphatase SHP-1 (PMID:11389028, PMID:12115647, PMID:12928397, PMID:22068234). This bidirectional output underlies opposing cell-type-specific roles: CD84 sustains prolonged T:B cell contact required for T follicular helper function and germinal center formation (PMID:20153220), drives EAT-2/Vav-1-dependent NK cytotoxicity (PMID:20962259), and amplifies TLR4/LPS-induced MAPK and NF-κB signaling in macrophages through the second ITSM tyrosine Y300 (PMID:20628063), yet negatively regulates FcεRI signaling in mast cells via Fes/SHP-1 (PMID:22068234) and suppresses IL-10-producing regulatory B cells through c-Maf (PMID:33767202). In disease, homophilic CD84 trans-interactions bridge chronic lymphocytic leukemia cells to their stromal microenvironment to promote survival and upregulate PD-L1/PD-1 checkpoint expression (PMID:27452524, PMID:30277471), platelet-derived soluble CD84 shed by ADAM10 enhances T cell motility to drive cerebral thromboinflammation after stroke (PMID:23025437, PMID:32762491), and in AML CD84 sustains leukemic survival through NRF2-dependent redox/mitochondrial homeostasis and SAP/Akt-driven NHEJ DNA repair (PMID:40198133, PMID:40633676).

Mechanistic history

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

    Establishing that CD84 is its own ligand answered whether this orphan SLAM-family receptor signals through homophilic contact, and localized recognition to a single Ig domain.

    Evidence Soluble CD84-Ig fusion binding, anti-CD84 domain-1 mAb blocking, and human/mouse domain chimeras

    PMID:11564780

    Open questions at the time
    • Did not resolve the structural basis or affinity of the homophilic interaction
    • Cytoplasmic signaling output not addressed
  2. 2002 High

    Identifying SAP and EAT-2 recruitment to the phosphorylated cytoplasmic tail defined the intracellular signaling adaptors that link CD84 ligation to downstream events in B cells.

    Evidence Yeast two-hybrid, COS transfection, and co-immunoprecipitation of SAP and EAT-2 from primary human B cells after mAb ligation

    PMID:11389028 PMID:12115647

    Open questions at the time
    • Specific tyrosine residues and the kinase responsible were not yet mapped
    • Functional consequence of adaptor recruitment unresolved
  3. 2003 High

    Mapping SAP recruitment to CD84 Y262 and SAP R32 and identifying Lck as the kinase established the precise phospho-tyrosine switch driving positive signaling.

    Evidence Site-directed mutagenesis of CD84 and SAP, in vitro phosphorylation, and T cell proliferation assays in SAP-deficient XLP patient cells

    PMID:12928397

    Open questions at the time
    • SAP-independent proliferation pathway not mechanistically defined
    • Did not address inhibitory signaling outputs
  4. 2007 High

    The 2.0 Å crystal structure and solution Kd answered how CD84 achieves homophilic specificity, revealing an orthogonal dimer with an interface that excludes heterodimers.

    Evidence X-ray crystallography of the Ig variable domain and analytical ultracentrifugation

    PMID:17563375

    Open questions at the time
    • Did not capture full-length receptor or cytoplasmic conformation
    • In situ clustering geometry at cell contacts not resolved
  5. 2010 High

    Genetic and imaging studies established CD84 as a physiological mediator of sustained T:B contact required for germinal center formation, giving the homophilic receptor an in vivo developmental function.

    Evidence In vivo immunization of CD84-deficient mice, in vitro conjugation assays, and intravital two-photon microscopy

    PMID:20153220

    Open questions at the time
    • Contribution of CD84 separated only partially from Ly108
    • Downstream signaling sustaining contact not detailed
  6. 2008 High

    Discovering that CD84 inhibits FcεRI signaling in mast cells revealed that the same receptor can produce inhibitory output, and that this is SAP-independent.

    Evidence CD84 transfection in RBL-2H3 cells, tyrosine mutagenesis (Y279F, ΔY324), and MAPK/degranulation assays

    PMID:18243321

    Open questions at the time
    • Inhibitory effector not yet identified
    • Mechanism in primary human mast cells untested
  7. 2011 High

    Identifying Fes and SHP-1 as the inhibitory mediators in human mast cells defined the alternative effector arm of CD84 signaling distinct from SAP/EAT-2.

    Evidence Co-cross-linking of FcεRI and CD84 in LAD2 and primary human mast cells, calcium flux, and Fes co-expression/phosphorylation

    PMID:22068234

    Open questions at the time
    • What determines positive versus inhibitory adaptor selection across cell types is unresolved
    • Stoichiometry of Fes/SHP-1 recruitment not quantified
  8. 2010 High

    Demonstrating Y300-dependent amplification of TLR4 signaling in macrophages extended CD84 function beyond adhesion into innate immune signal modulation via the second ITSM.

    Evidence CD84 transfection and Y300 mutagenesis in RAW-264.7 cells, MAPK/NF-κB and cytokine assays, and siRNA knockdown in BMDMs

    PMID:20628063

    Open questions at the time
    • Adaptor coupling Y300 to MAPK/NF-κB not identified
    • Ligand triggering CD84 in macrophages not defined
  9. 2010 High

    Showing EAT-2A/B are required for CD84-dependent NK cytotoxicity placed CD84 in an activating NK pathway acting through Vav-1.

    Evidence EAT-2A/B-deficient mice, NK cytotoxicity assays, and Vav-1 phosphorylation analysis

    PMID:20962259

    Open questions at the time
    • Did not separate EAT-2A from EAT-2B contributions fully
    • Relevant NK target ligand context not defined
  10. 2012 High

    Defining ADAM10 as the platelet CD84 sheddase and calpain as the intracellular protease established post-translational regulation generating soluble CD84.

    Evidence ADAM10-KO, ADAM17-KO, and calpain-inhibitor-treated platelets with biochemical and plasma analysis

    PMID:23025437

    Open questions at the time
    • Functional role of soluble CD84 not yet established
    • Trigger for constitutive shedding not defined
  11. 2016 Medium

    Identifying homophilic CD84 bridging between CLL cells and stroma defined a tumor-microenvironment survival circuit and a therapeutic target.

    Evidence CLL-stroma co-culture and in vivo CD84-blocking antibody with survival readouts

    PMID:23435417 PMID:27452524

    Open questions at the time
    • MIF/CD74-to-Bcl-2/Mcl-1 pathway placement partly correlative
    • Direct signaling intermediates downstream of stromal CD84 not detailed
  12. 2018 High

    Linking CD84 cell-cell interaction to PD-L1/PD-1 upregulation connected CD84 adhesion to immune checkpoint induction in CLL.

    Evidence CD84 blocking/KO in human and mouse CLL models with PD-L1/PD-1 flow cytometry and T cell assays

    PMID:30277471

    Open questions at the time
    • Signaling pathway from CD84 to PD-L1 transcription not mapped
    • Generality beyond CLL untested at this stage
  13. 2020 High

    Cell-type-specific knockouts showed platelet-derived soluble CD84 drives T cell motility, mechanistically connecting CD84 shedding to thromboinflammatory stroke injury.

    Evidence Platelet- and T cell-specific CD84 conditional KO mice, in vitro sCD84 motility assays, tMCAO stroke model

    PMID:32762491

    Open questions at the time
    • Signaling triggered in T cells by sCD84 not detailed
    • Whether shed monomer or oligomer drives motility unresolved
  14. 2021 High

    Demonstrating that SLAMF5 negatively controls IL-10-producing Bregs via c-Maf defined an immunoregulatory brake relevant to autoimmunity.

    Evidence SLAMF5 conditional B cell KO in EAE, in vitro blocking in mouse and human B cells, c-Maf analysis

    PMID:33767202

    Open questions at the time
    • Signaling adaptor coupling SLAMF5 to c-Maf suppression not identified
    • Relationship to the SAP/Fes switch unresolved
  15. 2025 High

    Identifying NRF2/Akt-redox and SAP/Akt/NHEJ pathways established CD84 as a survival dependency in AML, broadening its role to leukemic metabolism and DNA repair.

    Evidence CD84 knockdown/overexpression in human AML cells and PDX, mitochondrial and NRF2/Akt analysis, SAP co-IP, NHEJ factor and γH2AX readouts, MLL-AF9 and inv(16) mouse models

    PMID:40198133 PMID:40633676

    Open questions at the time
    • Two distinct mechanisms (NRF2/metabolism vs SAP/NHEJ) not reconciled into one model
    • Upstream ligand engaging CD84 in AML cells not defined
  16. 2025 High

    Defining a SLAMF5-BHLHE40-CD52 axis in myeloid cells extended CD84 function to microglial/macrophage activation and neuroinflammation.

    Evidence Myeloid-specific SLAMF5 KO in EAE, BHLHE40/CD52 analysis, pharmacological brain blockade, MS patient iPSC-microglia and monocytes

    PMID:40920820

    Open questions at the time
    • Proximal signaling linking SLAMF5 engagement to BHLHE40 not mapped
    • Ligand for myeloid SLAMF5 in CNS not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • What molecular logic determines whether CD84 engages positive (SAP/EAT-2) versus inhibitory (Fes/SHP-1) effectors in a given cell type, and how isoform-specific cytoplasmic tails tune this, remains unresolved.
  • No unifying model linking cell context to adaptor selection
  • Functional consequences of the five cytoplasmic isoforms untested in physiological settings
  • Endogenous ligand/trigger in non-immunological-synapse contexts undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3
Partners
CD84FESLCKPTPN6SH2D1ASH2D2AVAV1

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
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, establishing CD84 as its own ligand. Blocking with anti-CD84 mAbs recognizing epitopes in domain 1 abolished this binding, and CD84/mouse chimeras showed only the first extracellular Ig-like domain mediates ligand-receptor recognition. The CD84-CD84 interaction was independent of its cytoplasmic tail. Soluble Ig fusion protein binding assay, anti-CD84 mAb blocking, human/mouse domain chimeras Journal of immunology High 11564780
2001 CD84 cytoplasmic tail recruits SAP (SH2D1A, the X-linked lymphoproliferative disease gene product) via phosphorylated tyrosine residues in its cytoplasmic tail; recruitment is most efficient when specific tyrosine residues are phosphorylated, as demonstrated by yeast two-hybrid, COS cell transfection assays, and experiments in lymphoid cells. Yeast two-hybrid, COS cell transfection, co-immunoprecipitation in lymphoid cells Blood High 11389028
2002 CD84 is rapidly tyrosine phosphorylated following antibody ligation on B cells and recruits the cytoplasmic adaptor proteins SAP and EAT-2 via phosphorylated tyrosine residues in its cytoplasmic tail, as shown in primary human B cells. Anti-CD84 mAb ligation, tyrosine phosphorylation assay, co-immunoprecipitation of SAP and EAT-2 European journal of immunology High 12115647
2003 SAP recruitment to CD84 requires tyrosine phosphorylation of CD84, is mediated specifically by Y262 within the CD84 cytoplasmic domain and by R32 within the SH2 domain of SAP. The Src kinase Lck is required for CD84 tyrosine phosphorylation upon receptor ligation in activated T cells. CD84 ligation also enhances T cell proliferation via a SAP-independent mechanism. Site-directed mutagenesis of CD84 (Y262) and SAP (R32), in vitro phosphorylation, co-immunoprecipitation, T cell proliferation assay using SAP-deficient XLP patient 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. Solution studies showed CD84 self-associates with a Kd in the submicromolar range. Structural and chemical differences in the homophilic interfaces provide a mechanism to prevent formation of undesired heterodimers among SLAM family homophilic receptors. X-ray crystallography (2.0 Å), analytical ultracentrifugation for solution Kd measurement Proceedings of the National Academy of Sciences of the United States of America High 17563375
2010 CD84 is required for prolonged T cell:B cell contact, optimal T follicular helper function, and germinal center formation in vivo. While T cell:DC interactions were primarily integrin-dependent, T cell:B cell interactions had an early integrin-dependent phase and a sustained SAP- and CD84-dependent phase. Both CD84 and Ly108 mediated T cell adhesion and participated in stable T cell:B cell interactions in vitro. In vivo immunization of CD84-deficient mice, in vitro T cell:B cell conjugation assays, intravital two-photon microscopy Immunity High 20153220
2010 Mouse CD84 modulates TLR4-downstream signaling in macrophages: transfection of CD84 in RAW-264.7 macrophages increased MAPK phosphorylation and NF-κB activation upon LPS stimulation and altered cytokine secretion (increased TNF-α and MCP-1, decreased IL-10 and IL-6). This modulatory effect was dependent on Y300 within the second ITSM of CD84. CD84 knockdown in bone marrow-derived macrophages decreased TNF-α and IL-6 production. CD84 transfection in RAW-264.7 cells, site-directed mutagenesis (Y300), MAPK/NF-κB phosphorylation assays, cytokine ELISA, CD84 siRNA knockdown in BMDMs Journal of leukocyte biology High 20628063
2010 EAT-2A and EAT-2B adapters are positive regulators of CD84-dependent NK cell cytotoxicity in C57BL/6 mice. NK cells from EAT-2A- and EAT-2A/B-deficient mice were unable to kill tumor cells in a CD84-dependent manner. EAT-2A/B positively regulate phosphorylation of Vav-1 downstream of CD84. EAT-2A/B-deficient mouse generation (CRISPR/gene targeting in C57BL/6 ES cells), NK cell cytotoxicity assays, Vav-1 phosphorylation analysis Journal of immunology High 20962259
2008 CD84 inhibits FcεRI-mediated mast cell degranulation through homophilic interaction in CD84-transfected RBL-2H3 cells. This inhibition involves phosphorylation of Dok-1 and c-Cbl and impairs MAP kinase phosphorylation (ERK1/2, JNK, p38) and cytokine synthesis. CD84 mutants at tyrosines Y279F and ΔY324 reversed the inhibitory profile, and the mechanism is independent of SAP and SHP-2 recruitment. CD84 transfection in RBL-2H3 cells, site-directed mutagenesis (Y279F, ΔY324), Western blot for Dok-1/c-Cbl phosphorylation, MAPK phosphorylation assays, degranulation assays Molecular immunology High 18243321
2011 In human mast cells, CD84 is tyrosine phosphorylated upon FcεRI engagement, inhibits FcεRI-mediated calcium mobilization and the Syk-LAT-PLCγ1 signaling axis, and reduces degranulation and cytokine (IL-8, GM-CSF) release. The inhibitory mechanism is SAP- and EAT-2-independent but depends on the inhibitory kinase Fes (which phosphorylates the inhibitory ITSM motif on CD84 and itself becomes phosphorylated upon CD84 coexpression) and SHP-1. Co-cross-linking of FcεRI and CD84 in LAD2 and primary CD34+-derived human mast cells, calcium flux assay, phosphorylation assays, Fes co-expression/phosphorylation experiments Journal of immunology High 22068234
2012 CD84 on platelets is subject to dual regulation by ectodomain shedding and intracellular cleavage. ADAM10 is the principal sheddase responsible for CD84 ectodomain cleavage (ADAM17 is dispensable), while calpain mediates intracellular cleavage of the CD84 C-terminus simultaneously with but independently of ectodomain shedding. CD84 is also constitutively shed from the platelet surface by ADAM10 in vivo. Biochemical shedding assays, ADAM10-deficient, ADAM17-deficient, and calpain-inhibitor-treated mouse and human platelets, Western blot, plasma/serum analysis from transgenic mice Journal of thrombosis and haemostasis High 23025437
2013 In CLL, CD84 expression is regulated by macrophage migration inhibitory factor (MIF) and its receptor CD74. Activation of surface CD84 initiates a signaling cascade that enhances CLL cell survival. Downmodulation of CD84 or its immune-mediated blockade induces cell death in vitro and in vivo. Downstream, CD84 activation correlates with Bcl-2 and Mcl-1 expression. CD84 knockdown/blocking antibody in CLL cells in vitro and in vivo, MIF/CD74 stimulation assays, Bcl-2/Mcl-1 protein level measurements, clinical sample analysis (milatuzumab trial) Oncogene Medium 23435417
2015 SLAMF1, SLAMF5, and SLAMF6 act as negative regulators of humoral immunity. In triple knockout mice, both T-dependent and T-independent antibody responses were approximately twofold higher. Adoptive co-transfer experiments showed both [Slamf1+5+6]-/- B and T cells contributed to enhanced responses, with B cell-intrinsic activity being more pronounced. SLAMF5-deficient B cells enhanced T-independent type 2 antigen responses, indicating a B cell-intrinsic suppressive role. Triple knockout mice (Slamf1/5/6), adoptive co-transfer assays, T-dependent and T-independent immunization, anti-SLAMF6 mAb treatment Frontiers in immunology Medium 25926831
2015 B cell-intrinsic expression of CD84 (and Ly108) at germinal center B cells maintains B cell tolerance. Overexpression of B6 alleles of CD84 and Ly108 on autoimmune-prone B6.Sle1b background reduced GC response and autoantibody production. Lupus-associated CD84/Ly108 alleles on GC B cells were sufficient to break B cell tolerance. B6.Sle1b B cells showed reduced BCR signaling and lower B cell-T cell conjugate frequency. BAC-transgenic mice overexpressing B6 alleles of CD84 and Ly108, autoantibody ELISA, GC B cell analysis by flow cytometry, B cell-T cell conjugate assay, BCR signaling assay Journal of immunology Medium 25801429
2016 CD84 expressed on CLL cells interacts homophilically with CD84 on stromal microenvironment cells, promoting survival signaling in both CLL and stromal cells. Blocking CD84 in vitro and in vivo disrupts CLL-microenvironment interaction and induces cell death in CLL cells. In vitro co-culture of CLL cells with stromal cells, CD84-blocking antibody in vitro and in vivo CLL mouse model, cell death/survival assays Oncogene Medium 27452524
2016 CRISPR-mediated triple disruption of Slamf1, Slamf5, and Slamf6 in mice worsened iNKT cell developmental defects seen in SLAMF6 single gene-targeted mice, supporting positive signaling roles for these receptors and potential functional redundancy among them in iNKT development. Cas9/CRISPR triple knockout generation in C57BL/6 mice, flow cytometric analysis of iNKT and conventional lymphocyte populations PloS one Medium 27258160
2018 Cell-cell interaction mediated through CD84 upregulates PD-L1 expression on CLL cells and their microenvironment, and upregulates PD-1 expression on T cells. This resulted in suppression of T cell responses in vitro and in vivo, establishing CD84 as a regulator of PD-1/PD-L1 immune checkpoint expression in CLL. CD84 homophilic cell-cell interaction assays, CD84 blocking/KO in human and mouse CLL models in vitro and in vivo, PD-L1/PD-1 expression by flow cytometry, T cell functional assays The Journal of clinical investigation High 30277471
2020 CD84 on platelets drives cerebral thromboinflammation after ischemic stroke. Platelet-derived soluble CD84 (shed by ADAM10) enhances motility of wild-type but not CD84-deficient CD4+ T cells in vitro, demonstrating that homophilic CD84 interactions between platelet-derived sCD84 and T cell-expressed CD84 drive T cell migration. CD84 conditional knockout mice (platelet- or T cell-specific), in vitro T cell motility assay with platelet-derived sCD84, experimental stroke (tMCAO) model, flow cytometry for T cell infiltration, clinical sample analysis Circulation research High 32762491
2021 SLAMF5 (CD84) negatively controls the survival and function of IL-10-producing regulatory B cells. SLAMF5 deficiency in B cells causes accumulation of IL-10+ Bregs in EAE. Blocking SLAMF5 in vitro induces IL-10-producing Breg cells and increases their survival with a concomitant increase in transcription factor c-Maf. In vivo SLAMF5 blocking elevates IL-10+ Breg levels and ameliorates EAE severity. SLAMF5 conditional B cell knockout in EAE model, in vitro SLAMF5 blocking antibody in human and mouse B cells, c-Maf expression analysis, in vivo blocking experiment Nature communications High 33767202
2021 In multiple myeloma, tumor cells secrete MIF, which induces CD84 expression on microenvironmental cells. CD84 activation on these cells elevates expression of genes regulating differentiation toward M-MDSCs and G-MDSCs and upregulates PD-L1 expression on MDSCs, which suppresses T cell function. Downregulation or blocking of CD84 reduces MDSC accumulation and elevated T cell activity. MIF stimulation of microenvironment cells, CD84 knockdown/blocking antibody, MDSC differentiation assays, PD-L1 expression by flow cytometry, T cell functional assays, in vivo tumor models JCI insight Medium 33465053
2024 CD84 is a substrate/target of BTK kinase in neutrophils during alcohol-induced granulopoiesis. BTK inhibition (evobrutinib) or myeloid-specific Btk knockout reduced granulopoiesis and liver neutrophil infiltration in alcohol-associated hepatitis. CD84 was identified as a BTK substrate by liquid chromatography-tandem mass spectrometry, and CD84-blocking antibody inhibited alcohol-induced IL-1β and TNF-α in primary human neutrophils. LC-MS/MS kinase substrate identification, BTK inhibitor treatment, Btk myeloid-specific KO mice, CD84-blocking antibody in primary human neutrophils, cytokine ELISA Science translational medicine Medium 39110779
2024 CD84 induces a signaling cascade in regulatory B cells (Bregs) in triple-negative breast cancer involving the β-catenin and Tcf4 pathway, leading to transcription of IL-10 by direct binding to the IL-10 promoter and the promoter of its regulator AhR. This expands Bregs and suppresses anti-tumor immune activity. CD84 manipulation in Bregs, β-catenin/Tcf4 pathway analysis, promoter binding (ChIP or reporter assay implied), IL-10 production assays, immune cell activity assays, in vivo TNBC models Cell reports Medium 39466774
2024 CCL2-secreted by mesenchymal glioma stem cells induces IKZF1 expression, which promotes CD84 expression on tumor-associated macrophages. CD84 activates the SHP2 pathway to drive M2 polarization of TAMs. GSC-TAM co-culture, CCL2 stimulation, IKZF1 knockdown/inhibition, CD84 expression analysis, SHP2 pathway assays, animal glioma models with IKZF1 inhibitors Oncogene Medium 39112517
2025 In AML, CD84 regulates energy metabolism and mitochondrial dynamics. CD84 depletion altered mitochondrial ultrastructure and function, caused downmodulation of oxidative phosphorylation and fatty acid oxidation pathways, blocked Akt phosphorylation, and downmodulated NRF2. Conversely, CD84 overexpression stabilized NRF2 and promoted its transcriptional activation, supporting redox homeostasis and mitochondrial function. CD84 loss blocked leukemia engraftment and clonogenicity in MLL-AF9 and inv(16) AML mouse models. CD84 knockdown in human AML cell lines and PDX cells, CD84 overexpression, Akt/NRF2 pathway analysis, mitochondrial ultrastructure/function assays (electron microscopy implied), AML mouse models (MLL-AF9, inv(16)) The Journal of clinical investigation High 40198133
2025 CD84 promotes AML cell growth via the NHEJ DNA repair pathway. CD84 recruits SAP and activates the AKT signaling pathway to promote expression of NHEJ core factors (PRKDC, LIG4, XRCC5, DCLRE1C). Knockdown of CD84 inhibits NHEJ repair, leading to double-strand break accumulation and apoptosis. CD84 is required for proliferation and self-renewal of human leukemia-initiating cells. CD84 knockdown in AML cell lines and xenograft models, SAP co-immunoprecipitation, AKT pathway analysis, NHEJ factor expression analysis, DSB accumulation (γH2AX), LIC functional assays Molecules and cells Medium 40633676
2025 SLAMF5 deficiency in myeloid cells (microglia and macrophages) leads to decreased expression of activation and costimulatory molecules including MHC class II and CD80 in EAE. This downregulation is mediated through transcription factor BHLHE40 and its regulation of CD52, resulting in delayed onset and reduced EAE progression. Pharmacological blockade of SLAMF5 in the brain halted disease progression. In human iPSC-derived microglia and MS patient monocytes, SLAMF5 blockade reduced HLA-DR, CD80, and CD52 expression. Total and brain-specific SLAMF5 myeloid conditional KO in EAE, BHLHE40 pathway analysis, pharmacological brain blockade, iPSC-derived microglia from MS patients, flow cytometry PLoS biology High 40920820
2000 CD84 exists as five isoforms (CD84a–e) generated by alternative exon usage, reading frame shifts, cryptic splice sites, or absence of splicing. The five isoforms differ in their cytoplasmic domains and contain differentially distributed potentially phosphorylatable residues, providing a potential mechanism to regulate signal transduction activity. cDNA library screening, RT-PCR, genomic structure determination (at least 8 exons identified) Tissue antigens Medium 10746783

Source papers

Stage 0 corpus · 51 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 317 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 47 27564082
2010 Mouse CD84 is a pan-leukocyte cell-surface molecule that modulates LPS-induced cytokine secretion by macrophages. Journal of leukocyte biology 46 20628063
2018 CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and autoimmune disorders. Clinical immunology (Orlando, Fla.) 45 30522694
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 38 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
2024 Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors. Cell reports. Medicine 28 38242120
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
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
2016 CRISPR-Mediated Triple Knockout of SLAMF1, SLAMF5 and SLAMF6 Supports Positive Signaling Roles in NKT Cell Development. PloS one 18 27258160
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
2022 CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis. Microbiology spectrum 14 35196822
2014 Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis. PloS one 14 25551754
2024 CCL2 mediated IKZF1 expression promotes M2 polarization of glioma-associated macrophages through CD84-SHP2 pathway. Oncogene 13 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
2025 Identification of CD84 as a potent survival factor in acute myeloid leukemia. The Journal of clinical investigation 7 40198133
2024 Terminal deoxynucleotidyl transferase and CD84 identify human multi-potent lymphoid progenitors. Nature communications 7 39003273
2024 In vivo Bruton's tyrosine kinase inhibition attenuates alcohol-associated liver disease by regulating CD84-mediated granulopoiesis. Science translational medicine 7 39110779
2019 Bone marrow dendritic cells support the survival of chronic lymphocytic leukemia cells in a CD84 dependent manner. Oncogene 6 31772329
2025 Targeting CD84 protein on myeloid-derived suppressor cells as a novel immunotherapy in solid tumors. Computer methods and programs in biomedicine 5 39847992
2025 Tumor-derived CD84 promotes growth of acute myeloid leukemia cells via regulating nonhomologous DNA end-joining pathway. Molecules and cells 2 40633676
2025 The immune receptor SLAMF5 regulates myeloid-cell mediated neuroinflammation in multiple sclerosis. PLoS biology 1 40920820
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
2026 CD84 is a specific target for acute myeloid leukemia CAR-T cell therapy. Nature communications 0 42098093
2026 HSP47 inhibitor Col003 attenuates thromboinflammation after cerebral ischemia-reperfusion by suppressing GPVI-mediated CD84 shedding in platelets. Molecular immunology 0 42172863
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 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

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