Affinage

CD48

CD48 antigen · UniProt P09326

Length
243 aa
Mass
27.7 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD48 is a GPI-anchored cell-surface glycoprotein of the CD2/SLAM family that functions as a multivalent co-stimulatory and adhesion molecule on hematopoietic cells, integrating signals that regulate T cell activation, NK cell cytotoxicity, innate lymphoid cell differentiation, and mast cell/eosinophil responses to bacterial pathogens. CD48 engages CD2 via a head-to-head interaction of its membrane-distal immunoglobulin domain with weak, rapidly dissociating affinity (~10⁴ M⁻¹), and this interaction enhances TCR signaling by recruiting CD48 into lipid raft microdomains where it shuttles the adaptor LAT and Lck to the TCR/CD3 complex in a CD2→CD48→LAT hierarchy (PMID:7697352, PMID:9881969, PMID:19494291). CD48 also serves as the primary ligand for 2B4 (CD244), through which it triggers NK cell cytotoxicity, IFN-γ production, and CD8⁺ T cell proliferation, and homotypic 2B4–CD48 interactions on innate lymphoid cell precursors direct ILC2 differentiation (PMID:9834056, PMID:10359122, PMID:15905190, PMID:33219153). CD48 surface expression is epigenetically controlled by H3K27 methylation/demethylation (KDM6A/EZH2) and H3K27 deacetylation (HO-1/Sirt1), and by DNA methylation, mechanisms exploited by tumor cells for NK immune evasion (PMID:38355622, PMID:36058936, PMID:31922199).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1994 Medium

    Before CD48's functional role was clear, demonstrating that soluble CD48 engagement of CD2 on B cells prevented antigen-induced apoptosis and upregulated Bcl-2 established that the CD2–CD48 axis delivers survival signals beyond simple adhesion.

    Evidence Soluble recombinant CD48 treatment of mouse B cells with apoptosis/Bcl-2 readouts and anti-CD48 blockade

    PMID:7925579

    Open questions at the time
    • Downstream signaling intermediates between CD2 engagement and Bcl-2 upregulation not identified
    • Limited to B cells; generalizability to other lineages untested
  2. 1995 High

    Identifying the CD2-binding site on the GFCC'C'' β-sheet of CD48's membrane-distal Ig domain through complementary charge-swap mutagenesis established the head-to-head topology of the CD2–CD48 complex spanning ~134 Å, defining the structural framework for all subsequent interaction studies.

    Evidence Complementary mutagenesis of rat CD2 and CD48 extracellular domains with structural modeling

    PMID:7697352

    Open questions at the time
    • No high-resolution co-crystal structure at the time
    • Rat system; human interface details inferred
  3. 1996 High

    Single-molecule force measurements and SPR quantified the CD2–CD48 bond as weak and rapidly dissociating (~7.8 s⁻¹ off-rate, ~10⁴ M⁻¹ affinity), resolving how this interaction enables dynamic T cell scanning rather than stable adhesion.

    Evidence Flow chamber single-bond kinetics and surface plasmon resonance with purified rat CD2/CD48

    PMID:8986773 PMID:9188168

    Open questions at the time
    • Measurements performed with rat proteins; human kinetics not yet determined
    • How weak affinity translates to functional signaling thresholds in vivo remained unclear
  4. 1998 High

    Three concurrent advances established CD48's dual receptor partnerships and functional consequences: identification of 2B4 (CD244) as a second counter-receptor for CD48, demonstration that CD48 on APCs co-stimulates antigen-specific T cell activation via CD2, and the discovery that GPI-anchored CD48 enhances TCR signaling through lipid raft-dependent recruitment of TCR-ζ to the actin cytoskeleton.

    Evidence CD48-Ig fusion binding/IP identifying 2B4; CHO transfectant co-stimulation assays with anti-CD2 blockade; lipid raft fractionation and ζ-chain phosphorylation analysis

    PMID:9834056 PMID:9862369 PMID:9881969

    Open questions at the time
    • Relative contributions of CD2 vs 2B4 engagement to downstream signaling not delineated
    • Signaling intermediates between CD48 raft association and ζ phosphorylation unknown
  5. 1999 High

    CD48 knockout mice showed severely impaired CD4⁺ T cell activation to mitogens, anti-CD3, and alloantigens, providing genetic proof that CD48 is required on both T cells and APCs for efficient TCR signaling in vivo.

    Evidence Gene-targeted CD48⁻/⁻ mice with T cell proliferation, MLR, and reciprocal cell-mixing experiments

    PMID:9927686

    Open questions at the time
    • NK cell phenotype in CD48⁻/⁻ mice not characterized in this study
    • Whether CD48 loss affects thymic selection not addressed
  6. 1999 High

    Demonstrating that human 2B4 binds CD48 with high affinity and that CD48 engagement triggers NK cytotoxicity and IFN-γ production established the CD48–2B4 axis as a principal activating pathway for human NK cells.

    Evidence Soluble NAIL-Fc binding assay; NK cytotoxicity and IFN-γ measurement with CD48 protein and anti-2B4 mAb ligation

    PMID:10359122 PMID:10556801

    Open questions at the time
    • SAP-dependent vs SAP-independent signaling downstream of 2B4 not resolved
    • Whether 2B4 can also deliver inhibitory signals (as later shown in XLP) not yet addressed
  7. 2000 High

    Immunogold EM and confocal microscopy showed CD48 co-clusters with IL-2Rα and HLA in cholesterol-dependent lipid raft microdomains (~600–800 nm), and cholesterol depletion dispersed these clusters, establishing the biophysical basis for CD48's role as a raft-resident signaling organizer.

    Evidence Immunogold EM and confocal on T lymphoma cells; cholesterol depletion with filipin and methyl-β-cyclodextrin

    PMID:10823948

    Open questions at the time
    • Dynamic behavior of CD48 in rafts during active signaling not captured
    • Whether CD48 itself nucleates raft assembly or is passively recruited unknown
  8. 2003 Medium

    Discovery that CD48 on mast cells directly binds Mycobacterium tuberculosis and mediates histamine release revealed an unexpected innate immune function for CD48 as a bacterial pattern recognition receptor, extending its role beyond lymphocyte co-stimulation.

    Evidence Confocal microscopy of CD48 aggregation at mycobacterial binding sites; anti-CD48 blockade of histamine release

    PMID:12759438

    Open questions at the time
    • Specific mycobacterial ligand recognized by CD48 not identified
    • Single lab; no independent confirmation at the time
  9. 2005 High

    Multiple studies showed that homotypic 2B4–CD48 interactions among NK cells are essential for IL-2-driven NK expansion and that DC-subset-specific CD48 expression tunes whether 2B4 delivers activating or inhibitory signals, revealing context-dependent functional outcomes of the same receptor–ligand pair.

    Evidence 2B4-deficient NK cells with cytotoxicity/calcium/IFN-γ readouts and GFP-2B4 live imaging; NK:DC co-culture with XLP patient NK cells

    PMID:15905190 PMID:16148114

    Open questions at the time
    • Molecular switch between activating and inhibitory 2B4 signaling not fully resolved
    • Role of SAP/EAT-2 adaptor balance in determining outcome not mechanistically dissected
  10. 2005 Medium

    Co-immunoprecipitation of CD48 with IL-18Rα and the finding that GPI-anchor removal abolished IL-18-dependent tyrosine phosphorylation and IFN-γ production identified an unexpected role for CD48 in IL-18 receptor signaling, potentially through its GPI glycan.

    Evidence Co-IP from IL-18-stimulated KG-1 cells; phospholipase C treatment with functional readout

    PMID:15760905

    Open questions at the time
    • PLC treatment removes all GPI-anchored proteins, not just CD48
    • No reciprocal validation or CD48-specific knockdown to confirm specificity
  11. 2009 High

    Establishing the CD2→CD48→LAT signaling hierarchy at the TCR complex resolved how CD48 functions mechanistically as a molecular shuttle: CD2 first associates with TCR/CD3 and recruits CD48 and Lck, then CD48 brings LAT to the complex, which is required for IL-2 production.

    Evidence Sequential co-IP of TCR/CD3 complex components; CD48 siRNA knockdown with IL-2 functional readout in T cells

    PMID:19494291

    Open questions at the time
    • How GPI-anchored CD48 (lacking cytoplasmic tail) physically associates with LAT not mechanistically explained
    • Whether this hierarchy operates identically in CD8⁺ T cells not tested
  12. 2014 High

    Demonstrating that CD48 on eosinophils directly binds Staphylococcus aureus and its exotoxins, triggering degranulation confirmed in CD48⁻/⁻ mice, consolidated CD48's role as a bacterial sensor on innate immune cells beyond mast cells.

    Evidence Confocal imaging, anti-CD48 blockade, CD48⁻/⁻ mouse eosinophils, in vivo peritonitis model

    PMID:25255823

    Open questions at the time
    • Molecular identity of the bacterial surface moiety recognized by CD48 still unknown
    • Signaling pathway downstream of CD48 in eosinophils not characterized
  13. 2019 High

    A CMV-encoded soluble CD48 homolog (A43) that binds host 2B4 with high affinity and blocks NK immunological synapse formation provided evolutionary evidence that the CD48–2B4 axis is critical enough for antiviral immunity that viruses evolved a decoy to subvert it.

    Evidence SPR kinetics of viral A43–2B4 binding; NK conjugation, cytotoxicity, and IFN-γ assays

    PMID:30947296

    Open questions at the time
    • In vivo significance of A43 in CMV immune evasion not demonstrated
    • Whether other viral CD48 mimics exist not surveyed
  14. 2020 Medium

    Multiple groups showed that DNA methylation and the AML1-ETO/P300 axis regulate CD48 expression in leukemia, with hypomethylating agents or AML1-ETO restoring CD48 and NK killing, linking CD48 epigenetic silencing to tumor immune evasion.

    Evidence DNA methylation analysis with HMA treatment; AML1-ETO/P300 co-IP; NK co-culture cytotoxicity in vitro and in vivo AML models

    PMID:31922199 PMID:33225787

    Open questions at the time
    • Whether DNA methylation and histone modifications cooperate at the CD48 locus not addressed
    • Patient-level correlation between CD48 methylation and clinical outcome limited
  15. 2020 Medium

    Discovery that 2B4–CD48 interactions on innate lymphoid cell precursors direct ILC2 differentiation extended CD48's functional repertoire from mature effector cell co-stimulation to lineage specification of innate lymphoid cells.

    Evidence In vitro ILCP differentiation with 2B4/CD48 blocking antibodies; in vivo xenograft progenitor transfer

    PMID:33219153

    Open questions at the time
    • Downstream transcriptional program linking 2B4/CD48 to ILC2 commitment not identified
    • Single lab; independent replication lacking
  16. 2021 High

    Identifying GDF15 as a novel ligand for CD48 that stabilizes FOXP3 by suppressing STUB1-mediated ubiquitination revealed a previously unknown receptor function for CD48 in regulatory T cell biology, distinct from its CD2/2B4-binding roles.

    Evidence Co-IP, mass spectrometry, ChIP, RNA-seq, GDF15 KO mice, STUB1/FOXP3 protein stability assays

    PMID:34489334

    Open questions at the time
    • Binding interface between GDF15 and CD48 not structurally characterized
    • Whether GDF15–CD48 competes with CD2 or 2B4 binding not determined
    • Downstream signaling from GPI-anchored CD48 to STUB1 suppression unresolved
  17. 2022 High

    Convergent CRISPR screens and epigenetic dissection established that KDM6A demethylase maintains CD48 expression via H3K27me3 removal at the CD48 promoter, while HO-1/Sirt1-mediated H3K27 deacetylation suppresses it, defining a dual epigenetic rheostat controlling CD48-dependent immune recognition of tumor cells.

    Evidence Genome-wide CRISPR screens in ATLL and myeloma; ChIP-seq for H3K27me3; HO-1/Sirt1 co-IP; EZH2 and Sirt1 inhibitor rescue; NK ADCC and cytotoxicity assays

    PMID:35921533 PMID:36058936 PMID:38355622

    Open questions at the time
    • Interplay between KDM6A/EZH2 axis and HO-1/Sirt1 axis at the same locus not examined
    • Whether these epigenetic mechanisms are tumor-type-specific or general remains untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of the GDF15–CD48 interaction, how GPI-anchored CD48 (lacking a cytoplasmic domain) transduces intracellular signals to LAT or STUB1, the identity of bacterial surface moieties recognized by CD48, and whether the multiple epigenetic control mechanisms converge on a unified chromatin state at the CD48 locus.
  • No co-crystal structure of CD48 with any of its ligands
  • Signaling mechanism from GPI-anchor to intracellular effectors undefined
  • Bacterial ligands for CD48 unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 3
Partners
CD2CD244GDF15HMOX1IL18R1LATLCKSIRT1

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 The CD2-binding site on rat CD48 lies on the equivalent GFCC'C" beta-sheet of its membrane-distal immunoglobulin domain. Complementary mutations showed that two charged residues in CD48's ligand-binding site interact directly with two oppositely charged residues in CD2's ligand-binding site, establishing a head-to-head topology for the CD2-CD48 complex that spans approximately 134 Å. Complementary mutagenesis of CD2 and CD48 extracellular domains; structural modeling Current Biology High 7697352
1996 Single-molecule force measurements between surface-attached rat CD2 and CD48 showed that arrests were generated by single molecular bonds with an initial bond dissociation rate of ~7.8 s⁻¹, consistent with surface plasmon resonance affinity constants of ~10⁴ M⁻¹ and a weak, rapidly dissociating interaction. Flow chamber single-bond kinetics; surface plasmon resonance Proceedings of the National Academy of Sciences USA High 8986773
1997 Analytical ultracentrifugation (sedimentation equilibrium and velocity) of soluble recombinant rat CD2 and CD48 extracellular domains in free solution yielded dissociation constants of 20–110 µM, confirming the weak affinity of the CD2-CD48 interaction without artefacts from surface immobilisation. Analytical ultracentrifugation (sedimentation equilibrium and velocity) European Biophysics Journal High 9188168
1998 2B4 was identified as a novel counter-receptor (ligand) for murine CD48 by immunofluorescence and immunoprecipitation experiments using a chimeric CD48-IgG1 fusion protein. CD48-IgG1 fusion protein binding assay; immunofluorescence; immunoprecipitation Journal of Immunology High 9834056
1998 Engagement of GPI-linked CD48 on T cells by CD2 expressed on APCs enhances TCR-mediated signaling by qualitatively and quantitatively increasing lipid raft-dependent association of the TCR zeta chain with the actin cytoskeleton and zeta tyrosine phosphorylation, implicating lipid rafts as integration platforms for receptor signals and cytoskeletal reorganization. T cell:APC co-stimulation assay; lipid raft fractionation; actin cytoskeleton co-sedimentation; zeta chain phosphorylation analysis Immunity High 9881969
1998 CD48 expressed on antigen-presenting cells (CHO transfectants) enhances murine CD4+ T cell proliferation and IL-2 production in an antigen-specific manner, and this effect is mediated through CD2:CD48 interaction as shown by anti-CD2 mAb blockade; CD48 also increases T cell–APC conjugate formation. CHO transfectant co-stimulation assay; T cell proliferation; IL-2 ELISA; conjugate assay; blocking mAb European Journal of Immunology Medium 9862369
1999 Human 2B4 (NAIL/CD244) binds CD48 with high affinity as determined by soluble NAIL-Fc fusion protein; engagement of CD48 by recombinant CD48 protein increases NK cell cytotoxicity and induces IFN-γ production, and 2B4 ligation on human NK cells by CD48 or specific mAb triggers NK-mediated cytotoxicity. Soluble fusion protein binding assay; NK cytotoxicity assay; IFN-γ measurement; mAb ligation European Journal of Immunology High 10359122 10556801
1999 CD48-deficient mice generated by gene targeting show severely impaired CD4+ T cell activation (reduced proliferative responses to mitogens, anti-CD3 mAb, and alloantigen), demonstrating that CD48 is important on both T cells and antigen-presenting cells for T cell receptor signaling. Gene targeting (knockout mice); T cell proliferation assay; mixed lymphocyte reaction; mitogen stimulation; phorbol ester co-stimulation Proceedings of the National Academy of Sciences USA High 9927686
2000 CD48 co-localises and co-clusters with IL-2Rα and HLA molecules in cholesterol-rich lipid raft microdomains (~600–800 nm) on human T lymphoma cells, and disruption of membrane cholesterol with filipin or methyl-β-cyclodextrin disperses these clusters, establishing that CD48 resides in and requires intact lipid rafts for its membrane organisation. Immunogold electron microscopy; confocal microscopy; cholesterol depletion (filipin, methyl-β-cyclodextrin); cross-correlation analysis Proceedings of the National Academy of Sciences USA High 10823948
2001 2B4/CD48 interactions regulate CD8+ T cell proliferation; blocking with anti-2B4 antibody reduces proliferative responses, and this occurs even in the absence of APCs, indicating that 2B4 on activated/memory T cells can serve as a ligand for CD48 on neighboring T cells to provide costimulatory-like function. Anti-2B4 and anti-CD48 blocking antibodies; T cell proliferation assay; APC-free cultures Journal of Immunology Medium 11739483
2002 Direct force measurements confirmed that full-length extracellular domains of murine CD2 and CD48 adhere in a head-to-head orientation, that the CD2-CD48 bond generates weak adhesion, and that lateral receptor mobility is required for appreciable adhesion. Surface force apparatus (direct force measurements between protein-coated surfaces) Biochemistry High 12356317
2003 CD48 on mast cells mediates direct interaction with Mycobacterium tuberculosis: CD48 aggregates at sites of bacterial binding, and anti-CD48 antibodies inhibit mast cell histamine release in response to mycobacteria, indicating CD48 functions as a pattern recognition receptor for mycobacterial binding. Immunofluorescence microscopy (CD48 aggregation at bacterial binding sites); anti-CD48 antibody blockade; histamine release assay Journal of Immunology Medium 12759438
2005 Homotypic 2B4/CD48 interactions among NK cells are essential for IL-2-driven NK cell expansion and activation; in the absence of 2B4/CD48 interaction (using gene-deficient cells and mAbs), NK cytotoxicity, IFN-γ secretion, and calcium signaling are severely impaired, and GFP-tagged 2B4 localises specifically to NK-NK conjugation sites. 2B4-deficient NK cells; blocking mAbs; cytotoxicity assay; IFN-γ ELISA; calcium flux; GFP-2B4 live imaging of NK-NK conjugates; in vivo tumor clearance Blood High 15905190
2005 CD48 expression on dendritic cell subsets determines NK cell activation outcomes: monocyte-derived DCs and plasmacytoid DCs lack CD48, whereas blood/bone marrow myeloid DCs express it; NK cells are activated by CD48-expressing DCs but inhibited via 2B4 by CD48-expressing lymph node DCs, demonstrating that DC-subset-specific CD48 expression tunes 2B4-mediated NK activation or inhibition depending on anatomic context. Flow cytometry; NK:DC co-culture functional assays; IFN-γ production; NK cells from XLP patients (lacking SAP) Journal of Immunology Medium 16148114
2005 CD48 interacts with IL-18Rα via both the peptide portion and the GPI glycan; IL-18Rα co-immunoprecipitates with CD48 from IL-18-stimulated KG-1 cells. Phospholipase C treatment removing GPI-anchored proteins (including CD48) inhibits IL-18-dependent tyrosine kinase phosphorylation and IFN-γ production, indicating the CD48/GPI glycan complex is required for IL-18 signaling. Co-immunoprecipitation; phosphatidylinositol-specific phospholipase C treatment; tyrosine phosphorylation assay; IFN-γ production Journal of Biological Chemistry Medium 15760905
2006 CD48 is an IL-3-upregulated activation receptor on human eosinophils; cross-linking CD48 on eosinophils triggers granule protein release (degranulation), and CD48 is induced by allergen challenge in a murine asthma model, establishing CD48 as a functional activating receptor on eosinophils. Flow cytometry; IL-3 stimulation; CD48 cross-linking degranulation assay; murine asthma model; anti-IL-3 treatment Journal of Immunology Medium 16785501
2009 GPI-anchored CD48 (but not CD59) is recruited to the immobilised TCR/CD3 complex upon T cell activation. CD48 reorganisation is required for IL-2 production by mediating lateral association of the adaptor LAT with the TCR/CD3 complex. CD2 acts hierarchically upstream, associating with TCR/CD3 irrespective of CD48 and recruiting CD48 and Lck; CD48 in turn shuttles LAT to the complex. Co-immunoprecipitation; siRNA knockdown of CD48; IL-2 production assay; sequential co-IP establishing CD2→CD48→LAT hierarchy Journal of Immunology High 19494291
2013 ORMDL3 overexpression in eosinophils regulates IL-3-induced expression of CD48, and CD48-mediated eosinophil degranulation; ORMDL3 knockdown inhibits CD48 surface expression as well as activation-induced cell shape changes and recruitment to inflammation, placing ORMDL3 upstream of CD48 in eosinophil activation. ORMDL3 overexpression/knockdown in eosinophils; flow cytometry; degranulation assay; in vivo recruitment assay Nature Communications Medium 24056518
2014 CD48 on human and murine eosinophils directly binds Staphylococcus aureus and its exotoxins (SEB, protein A, peptidoglycan); SA/exotoxins enhance CD48 expression, aggregate at CD48 sites (confocal microscopy), and trigger eosinophil activation, degranulation, and cytokine release in a CD48-dependent manner confirmed in CD48-/- mouse bone marrow eosinophils. Confocal microscopy (CD48 aggregation at SA binding sites); blocking anti-CD48 antibody; CD48-/- mouse eosinophils; degranulation assay; cytokine ELISA; in vivo peritonitis model Clinical and Experimental Allergy High 25255823
2019 A cytomegalovirus-encoded soluble CD48 homolog (A43) binds host 2B4 with high affinity and slow dissociation (surface plasmon resonance), abrogates host CD48:2B4 interactions, reduces NK cell-target conjugate formation, prevents immunological synapse establishment, and severely impairs 2B4-mediated NK cytotoxicity and IFN-γ production — establishing CD48:2B4 as required for NK effector function. Surface plasmon resonance; NK cytotoxicity assay; conjugate formation assay; IFN-γ measurement; viral protein functional characterisation PLoS Pathogens High 30947296
2020 CD48 expression in AML is regulated by DNA methylation; a hypomethylating agent increases CD48 expression on AML cells, restoring NK cell killing in vitro, and CD48 high expression reverses AML immune evasion and activates NK cell function in vivo. DNA methylation analysis; hypomethylating agent treatment; NK co-culture cytotoxicity assay; in vivo AML mouse model Clinical Science Medium 31922199
2020 CD48 expression in human innate lymphoid cell precursors (ILCPs) modulates ILC differentiation: 2B4:CD48 interaction (between co-expressed 2B4 and CD48 on progenitors) specifically induces ILC2 differentiation in vitro, and CD48-expressing progenitors give rise to tissue-associated ILCs in vivo. In vitro progenitor differentiation assay; blocking antibodies against 2B4/CD48; in vivo xenograft (progenitor transfer); flow cytometry Science Immunology Medium 33219153
2021 GDF15 binds CD48 on T cells as a previously unrecognised receptor; GDF15:CD48 interaction downregulates STUB1 (an E3 ubiquitin ligase that mediates FOXP3 degradation), thereby stabilising FOXP3, promoting iTreg generation and enhancing nTreg suppressive function. Co-immunoprecipitation confirmed GDF15-CD48 physical interaction. Co-immunoprecipitation; RNA sequencing; mass spectrometry; ChIP; flow cytometry; GDF15 KO mouse model; STUB1/FOXP3 protein stability assays Journal for Immunotherapy of Cancer High 34489334
2022 Genome-wide CRISPR screen identified CD48 as the key determinant of ATLL cell susceptibility to NK cell-mediated cytotoxicity; CD48 knockout conferred resistance to NK killing, reduced IFN-γ induction and degranulation by primary NK cells, and primary ATLL cells showed reduced CD48 expression with disease progression. Genome-wide CRISPR knockout screen; primary NK cell cytotoxicity assay; IFN-γ and CD107a degranulation assays; flow cytometry of primary ATLL samples Blood High 35921533
2022 HO-1 overexpression in AML cells specifically downregulates CD48 expression by directly interacting with Sirt1, increasing its deacetylase activity, leading to H3K27 deacetylation at the CD48 promoter to suppress CD48 transcription; Sirt1 inhibition restores CD48 expression, confirming the HO-1→Sirt1→H3K27 deacetylation→CD48 suppression axis. Co-immunoprecipitation (HO-1/Sirt1); Western blot; qRT-PCR; flow cytometry; Sirt1 inhibitor rescue; NK co-culture cytotoxicity; in vivo AML mouse model Journal of Translational Medicine High 36058936
2024 KDM6A (H3K27me3 demethylase) epigenetically regulates CD48 expression: KDM6A loss increases H3K27me3 on the CD48 promoter, markedly downregulating CD48, which contributes to resistance to daratumumab-mediated ADCC in multiple myeloma. EZH2 inhibitor treatment restores CD48 (and CD38) expression and reverses ADCC resistance. Genome-wide CRISPR screen; ChIP-seq (H3K27me3 at CD48 promoter); EZH2 inhibitor rescue; NK ADCC assay; flow cytometry Nature Communications High 38355622
2020 AML1-ETO fusion oncoprotein increases CD48 expression on AML cells through AML1-ETO/P300-mediated acetylation of CD48, inhibiting NK cell immune evasion; this provides a mechanism for the better clinical outcomes observed in AML1-ETO-positive AML. Immunoprecipitation; Western blot; flow cytometry; NK co-culture cytotoxicity assay Leukemia and Lymphoma Medium 33225787
2019 TGF-β downregulates CD48 surface expression on leukemia cells (MEG-01 and U937), reducing their susceptibility to NK-92MI killing and conjugate formation; CD48 knockdown phenocopies TGF-β treatment, confirming CD48 as the relevant target for TGF-β-mediated NK evasion of leukemia cells. TGF-β treatment; CD48 knockdown; NK co-culture cytotoxicity assay; conjugate formation assay; flow cytometry Immunobiology Medium 31421859
1994 Occupancy of CD2 on mouse B cells by soluble recombinant mouse CD48 (its natural ligand) prevents antigen-induced apoptosis and upregulates Bcl-2 expression; anti-CD48 antibody abrogates allogeneic cell-induced clonal expansion, establishing that CD2-CD48 interaction controls B cell survival decisions. Soluble recombinant CD48 treatment; anti-CD48 blocking mAb; apoptosis (DNA fragmentation) assay; Bcl-2 Western blot European Journal of Immunology Medium 7925579

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic acids research 53619 9254694
2009 BLAST+: architecture and applications. BMC bioinformatics 14886 20003500
2002 BLAT--the BLAST-like alignment tool. Genome research 6485 11932250
2012 Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Science translational medicine 751 22593173
2012 Domain enhanced lookup time accelerated BLAST. Biology direct 623 22510480
2004 The biology of CML blast crisis. Blood 422 14982876
1981 A nuclear antigen associated with cell proliferation and blast transformation. The Journal of experimental medicine 350 6172535
1987 Chronic myelogenous leukemia in blast crisis. Analysis of 242 patients. The American journal of medicine 263 3477958
1998 Engagement of GPI-linked CD48 contributes to TCR signals and cytoskeletal reorganization: a role for lipid rafts in T cell activation. Immunity 210 9881969
1999 Activating interactions in human NK cell recognition: the role of 2B4-CD48. European journal of immunology 208 10359122
2016 Roles of CD48 in regulating immunity and tolerance. Clinical immunology (Orlando, Fla.) 171 26794910
2021 GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma. Journal for immunotherapy of cancer 134 34489334
2010 Recent advances in rice blast effector research. Current opinion in plant biology 132 20627803
1998 Identification of the 2B4 molecule as a counter-receptor for CD48. Journal of immunology (Baltimore, Md. : 1950) 130 9834056
2000 Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. Proceedings of the National Academy of Sciences of the United States of America 126 10823948
2020 Ferroptosis contributes to developmental cell death in rice blast. The New phytologist 123 32367535
2022 Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood 120 34111285
1995 Topology of the CD2-CD48 cell-adhesion molecule complex: implications for antigen recognition by T cells. Current biology : CB 119 7697352
2008 GeneCAT--novel webtools that combine BLAST and co-expression analyses. Nucleic acids research 116 18480120
2007 Susceptibility of rice to the blast fungus, Magnaporthe grisea. Journal of plant physiology 105 17905473
2019 RRM Transcription Factors Interact with NLRs and Regulate Broad-Spectrum Blast Resistance in Rice. Molecular cell 104 30975460
2016 Immunity to Rice Blast Disease by Suppression of Effector-Triggered Necrosis. Current biology : CB 98 27641772
2013 ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48. Nature communications 98 24056518
1994 Anti-CD2 receptor and anti-CD2 ligand (CD48) antibodies synergize to prolong allograft survival. The Journal of experimental medicine 95 7903681
2011 Factors affecting blast traumatic brain injury. Journal of neurotrauma 87 21861635
2019 Effector gene reshuffling involves dispensable mini-chromosomes in the wheat blast fungus. PLoS genetics 85 31513573
2014 EC-BLAST: a tool to automatically search and compare enzyme reactions. Nature methods 85 24412978
2011 genBlastG: using BLAST searches to build homologous gene models. Bioinformatics (Oxford, England) 83 21653517
1999 Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48. European journal of immunology 81 10556801
2023 UniProt Tools: BLAST, Align, Peptide Search, and ID Mapping. Current protocols 80 36943033
2003 Mast cell activation by Mycobacterium tuberculosis: mediator release and role of CD48. Journal of immunology (Baltimore, Md. : 1950) 80 12759438
2005 Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood 75 15905190
1999 CD48-deficient mice have a pronounced defect in CD4(+) T cell activation. Proceedings of the National Academy of Sciences of the United States of America 74 9927686
2016 Sequence Alignment and Homology Search with BLAST and ClustalW. Cold Spring Harbor protocols 71 27574197
2007 The Biology of CML blast crisis. Hematology. American Society of Hematology. Education Program 70 18024655
2010 GPU-BLAST: using graphics processors to accelerate protein sequence alignment. Bioinformatics (Oxford, England) 68 21088027
1996 Determination of the lifetime and force dependence of interactions of single bonds between surface-attached CD2 and CD48 adhesion molecules. Proceedings of the National Academy of Sciences of the United States of America 68 8986773
2009 Biomarkers of blast-induced neurotrauma: profiling molecular and cellular mechanisms of blast brain injury. Journal of neurotrauma 66 19422293
2010 CD48: A co-stimulatory receptor of immunity. The international journal of biochemistry & cell biology 62 20833258
2014 Genome-wide association study of blast resistance in indica rice. BMC plant biology 60 25403621
2016 Management of CML-blast crisis. Best practice & research. Clinical haematology 58 27839570
2001 Cutting edge: Regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions. Journal of immunology (Baltimore, Md. : 1950) 57 11739483
2015 Management of chronic myeloid leukemia in blast crisis. Annals of hematology 51 25814082
2006 CD48 is an allergen and IL-3-induced activation molecule on eosinophils. Journal of immunology (Baltimore, Md. : 1950) 51 16785501
1997 Detection of a soluble form of the leukocyte surface antigen CD48 in plasma and its elevation in patients with lymphoid leukemias and arthritis. Journal of clinical immunology 47 9418191
2018 Osmotic stabilization prevents cochlear synaptopathy after blast trauma. Proceedings of the National Academy of Sciences of the United States of America 42 29735658
2023 The OsBDR1-MPK3 module negatively regulates blast resistance by suppressing the jasmonate signaling and terpenoid biosynthesis pathway. Proceedings of the National Academy of Sciences of the United States of America 41 36952381
2014 Hippocampal vulnerability and subacute response following varied blast magnitudes. Neuroscience letters 40 24726403
2009 Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome. Journal of immunology (Baltimore, Md. : 1950) 40 19494291
1986 Biochemical analysis suggests distinct functional roles for the BLAST-1 and BLAST-2 antigens. Journal of immunology (Baltimore, Md. : 1950) 40 3081632
2014 Exacerbation of blast-induced ocular trauma by an immune response. Journal of neuroinflammation 37 25472427
2007 BLAST QuickStart: example-driven web-based BLAST tutorial. Methods in molecular biology (Clifton, N.J.) 37 17993672
1993 CD4+8- and CD4-8+ mature thymocytes require different post-selection processing for final development. Journal of immunology (Baltimore, Md. : 1950) 36 8101540
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