Affinage

CD48

CD48 antigen · UniProt P09326

Length
243 aa
Mass
27.7 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD48 is a GPI-anchored Ig-superfamily glycoprotein expressed broadly on hematopoietic cells that functions as a heterotypic adhesion and co-stimulatory ligand coordinating T cell, NK cell, and innate immune responses (PMID:1383383, PMID:1693656). It engages CD2 as a counter-receptor through a very low-affinity, fast-dissociating interaction (KD ~60–90 µM) mediated by the GFCC'C'' beta-sheet face of its membrane-distal Ig domain in a head-to-head docking topology, a binding mode confirmed biophysically and crystallographically as an unusually flat, charge-complementary surface (PMID:1383383, PMID:7903240, PMID:7697352, PMID:16803907). The same flat surface allows CD48 to cross-react with its higher-affinity ligand 2B4/CD244 (KD ~8–16 µM), and these CD48–2B4 interactions—including homotypic NK–NK engagement—drive NK cell cytotoxicity and IFN-γ production (PMID:9841922, PMID:15905190, PMID:16803907). In T cells, GPI-anchored CD48 is recruited to the immobilized TCR/CD3 complex downstream of CD2/Lck and is required for LAT association and IL-2 production, placing CD48 in a hierarchical co-stimulatory pathway that builds the early TCR signalosome (PMID:9927686, PMID:19494291). Beyond lymphocytes, CD48 acts as an activating receptor on eosinophils and mast cells, mediating recognition of bacterial pathogens including M. tuberculosis and S. aureus and triggering degranulation (PMID:12759438, PMID:16785501, PMID:25255823). CD48 surface expression is induced by type I/II interferons and IL-3 and is epigenetically repressed via H3K27me3 deposition on its promoter, an axis controlled by KDM6A/EZH2 and by DNA methylation that tumors exploit to evade NK-mediated killing (PMID:16785501, PMID:9041467, PMID:35921533, PMID:38355622). CD48 has additionally been identified as a receptor for GDF15 on T cells, linking tumor-derived signals to Treg-mediated immunosuppression (PMID:34489334).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 Medium

    Establishing CD48 as a cloned GPI-anchored leukocyte glycoprotein of the CD2/LFA3 Ig superfamily subgroup defined the molecular identity from which all functional studies proceeded.

    Evidence cDNA cloning, sequencing, and genetic linkage mapping of mouse BCM1/CD48

    PMID:1693656

    Open questions at the time
    • GPI anchor inferred structurally rather than directly demonstrated
    • no ligand or function assigned at this stage
  2. 1992 High

    Identifying CD48 as the counter-receptor for CD2 answered what physiological ligand engages this molecule and connected it to T cell adhesion.

    Evidence Chimeric CD2-IgG pulldown, protein microsequencing, and mAb blocking in T cell lines

    PMID:1383383

    Open questions at the time
    • affinity and kinetics of the interaction not quantified
    • binding interface not mapped
  3. 1993 High

    Quantitative SPR established that CD2–CD48 is an extremely low-affinity, fast-off-rate interaction, defining the biophysical regime of cell-surface adhesion-receptor recognition.

    Evidence Surface plasmon resonance with soluble recombinant proteins in both orientations; confirmed by analytical ultracentrifugation

    PMID:7903240 PMID:9188168

    Open questions at the time
    • does not explain how weak affinity is translated into productive signaling
    • structural basis of binding not resolved
  4. 1996 High

    Mapping the binding surface to the GFCC'C'' beta-sheet face on both CD48 and CD2 established the head-to-head docking topology and the structural origin of species specificity.

    Evidence Complementary charge-swap mutagenesis, heteronuclear NMR titration, and molecular modelling

    PMID:7697352 PMID:8634239

    Open questions at the time
    • high-resolution crystal structure not yet available
    • thermodynamic basis of recognition not determined
  5. 1998 High

    Identifying 2B4/CD244 as a second, higher-affinity ligand revealed that CD48 functions in more than one receptor axis and engages activating receptors beyond CD2.

    Evidence Recombinant 2B4 binding assays, anti-CD48 blocking, and SPR; independent CD48-IgG1 pulldown confirmation

    PMID:9834056 PMID:9841922

    Open questions at the time
    • downstream signaling of the 2B4–CD48 interaction not yet defined
    • relative physiological role of CD2 vs 2B4 engagement unclear
  6. 1999 High

    Genetic knockout demonstrated that CD48 is functionally required on both T cells and APCs for CD4+ T cell activation, and that CD48–2B4 engagement controls NK cytotoxicity and IFN-γ, moving CD48 from a binding partner to a causal regulator of immune function.

    Evidence CD48-deficient mice with proliferation/cell-mixing assays; NK cytotoxicity and IFN-γ assays with recombinant CD48 and NAIL/2B4 homologue

    PMID:10359122 PMID:10556801 PMID:9927686

    Open questions at the time
    • molecular mechanism linking GPI-anchored CD48 to TCR signaling not resolved
    • signaling events downstream of CD48 in APCs unmapped
  7. 2000 Medium

    Demonstrating that CD48 co-clusters with IL-2Rα and HLA in cholesterol-dependent lipid rafts provided a membrane-organization basis for how a GPI-anchored molecule participates in signaling.

    Evidence Immunogold/EM and confocal imaging with cholesterol depletion on T lymphoma cells

    PMID:10823948

    Open questions at the time
    • functional consequence of raft clustering for signaling not directly tested
    • single cell type examined
  8. 2006 High

    The crystal structure plus thermodynamic analysis explained how an unusually flat, charge-complementary CD48 surface enables cross-reactivity with both CD2 and 2B4, resolving the structural logic of dual ligand recognition.

    Evidence X-ray crystallography of rat CD48 receptor-binding domain with isothermal titration calorimetry; surface force measurements of CD2–CD48 adhesion

    PMID:12356317 PMID:16803907

    Open questions at the time
    • structure of the full CD48–2B4 complex not solved
    • structures from rat domains rather than human
  9. 2009 High

    Placing CD48 hierarchically downstream of CD2/Lck and upstream of LAT recruitment defined the mechanistic logic by which CD2 and CD48 cooperate to assemble the early TCR signalosome.

    Evidence Reciprocal Co-IP, CD48 knockdown/knockout T cells, LAT co-precipitation, and IL-2 readouts

    PMID:19494291

    Open questions at the time
    • how a GPI-anchored protein lacking a cytoplasmic tail transmits the signal not fully explained
    • physical link between CD48 and LAT not identified
  10. 2014 High

    Establishing CD48 as a receptor for whole bacteria and exotoxins on eosinophils and mast cells, and as a survival-modulating receptor on DCs, broadened CD48 function from lymphocyte co-stimulation to innate pathogen sensing and myeloid regulation.

    Evidence M. tuberculosis and S. aureus binding/degranulation assays with anti-CD48 blocking and CD48−/− eosinophils; SLAMF4/anti-SLAMF2 engagement of DCs

    PMID:12759438 PMID:16785501 PMID:24670806 PMID:25255823

    Open questions at the time
    • molecular details of bacterial ligand binding to CD48 not defined
    • signaling pathway from CD48 to degranulation unresolved
  11. 2020 High

    Defining IFN-, IL-3-, DNA-methylation- and KDM6A/EZH2-dependent control of CD48 surface expression established how CD48 levels are tuned and how tumors silence CD48 to escape NK-mediated and antibody-dependent killing.

    Evidence IFN/IL-3 induction assays; ORMDL3 manipulation; methylation and H3K27me3 ChIP with hypomethylating and EZH2-inhibitor rescue and NK/ADCC readouts in AML and myeloma

    PMID:16785501 PMID:24056518 PMID:31922199 PMID:38355622 PMID:9041467

    Open questions at the time
    • transcription factors directly driving CD48 from these signals not fully defined
    • relative contribution of DNA methylation vs H3K27me3 across tumor types unclear
  12. 2021 Medium

    Identifying CD48 as a receptor for GDF15 on T cells linked tumor-derived signals to Treg-mediated immunosuppression via STUB1/FOXP3, expanding CD48's ligand repertoire beyond Ig-superfamily counter-receptors.

    Evidence Co-IP/mass spectrometry receptor identification with downstream RNA-seq, ChIP, CyTOF and a GDF15-KO HCC model

    PMID:34489334

    Open questions at the time
    • GDF15–CD48 binding not independently replicated
    • structural basis of GDF15 engagement of CD48 unknown
  13. 2022 High

    Unbiased CRISPR screens nominated CD48 as the dominant determinant of tumor susceptibility to NK-cell killing, cementing the CD48–2B4 axis as a clinically relevant immune-evasion target.

    Evidence Genome-wide CRISPR knockout screens in ATLL lines with primary human NK cytotoxicity assays and patient samples

    PMID:35921533

    Open questions at the time
    • mechanism of CD48 loss in primary disease progression not defined
    • interplay between CD48 and other NK ligands not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a cytoplasmic-tail-less GPI-anchored CD48 physically transduces signals into the TCR signalosome and into innate effector pathways, and whether the GDF15–CD48 axis generalizes, remain open.
  • no defined cytoplasmic transducer for GPI-anchored CD48
  • GDF15–CD48 interaction awaits independent confirmation
  • no human-protein high-resolution structure of CD48–2B4 or CD48–GDF15 complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 2
Partners
CD2CD244GDF15

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 CD48 is the ligand (counter-receptor) for mouse CD2; identified by generating a chimeric CD2-IgG fusion protein that bound to CD48 on T cell lines, confirmed by protein microsequencing of the affinity-purified antigen, reactivity with recombinant CD48, and inhibition of CD2–CD48 binding by soluble CD48. CD48 is a GPI-anchored glycoprotein (~45 kD) predominantly expressed on hematopoietic cells. Chimeric CD2-IgG fusion protein pulldown, protein microsequencing, mAb inhibition assays, soluble recombinant protein competition The Journal of experimental medicine High 1383383
1993 Quantitative kinetic and affinity analysis of rat CD2–CD48 interaction by surface plasmon resonance (BIAcore) revealed a very low-affinity interaction (KD ~60–90 µM) driven by an extremely rapid off-rate (koff ≥ 6 s⁻¹), with a normal on-rate (kon ≥ 10⁵ M⁻¹s⁻¹). Glycosylation of CD2 had little effect on binding affinity. Surface plasmon resonance (BIAcore) with soluble recombinant proteins in both binding orientations The EMBO journal High 7903240
1995 The CD2-binding site on rat CD48 lies on the GFCC'C'' beta-sheet of its membrane-distal Ig domain (equivalent to the CD2 ligand-binding surface). Complementary charged-residue mutations in CD48 and CD2 demonstrated direct electrostatic contacts between the two binding surfaces, establishing a head-to-head docking topology. The modeled CD2–CD48 complex spans ~134 Å, similar to the predicted TCR–pMHC complex distance. Complementary site-directed mutagenesis of CD48 and CD2, functional binding assays, molecular modelling Current biology : CB High 7697352
1996 NMR titration of ¹⁵N-labelled rat CD2 domain 1 with soluble CD48 identified the CD48-binding surface of CD2 as the GFCC'C'' face (~700–800 Ų), with no large-scale structural changes in CD2 upon CD48 binding. Species- and ligand-specific binding differences between rat and human CD2 are explained by as few as three residues (Thr37, Leu38, Glu41 in rat; Lys42, Lys43, Gln46 in human). Heteronuclear NMR (²D ¹⁵N-¹H HSQC) titration with soluble CD48 Biochemistry High 8634239
1997 Analytical ultracentrifugation (sedimentation equilibrium and velocity) in free solution confirmed the weak affinity of the rat CD2–CD48 interaction (KD 20–110 µM at 5°C), ruling out significant self-association of either reactant as a confounding factor in SPR measurements. Analytical ultracentrifugation (sedimentation equilibrium and velocity) European biophysics journal : EBJ Medium 9188168
1998 2B4 (CD244) is an additional ligand for CD48: recombinant mouse 2B4 extracellular domain bound to CD48-expressing cells and this binding was blocked by anti-CD48 mAbs. Surface plasmon resonance showed mCD48 binds m2B4 with 6–9-fold higher affinity (KD ~16 µM at 37°C) than it binds CD2; human CD48 bound human 2B4 with KD ~8 µM. Fluorescent bead binding assay with recombinant 2B4, anti-CD48 mAb blocking, surface plasmon resonance The Journal of experimental medicine High 9841922
1998 CD48 fusion protein (CD48-IgG1) identified 2B4 as a novel counter-receptor of CD48 by immunofluorescence and immunoprecipitation, independently confirming the CD48–2B4 interaction. Chimeric CD48-IgG1 fusion protein pulldown, immunofluorescence, immunoprecipitation Journal of immunology (Baltimore, Md. : 1950) Medium 9834056
1990 Mouse BCM1/CD48 (also known as OX45/Blast-1) is a GPI-anchored glycoprotein expressed on leukocytes, cloned and sequenced. Genomic linkage analysis placed the Bcm-1 locus on distal mouse chromosome 1, linked to an ATPase alpha chain gene, establishing CD48 as a member of the CD2/LFA3 Ig superfamily subgroup. cDNA cloning and sequencing, genetic linkage mapping, pulse-field gel electrophoresis The Journal of experimental medicine Medium 1693656
1991 CD48 (Blast-1) is expressed on T cells and monocytes in addition to B cells. EBV transformation and PMA/IL-4/PHA stimulation increase surface CD48 expression by elevating steady-state CD48 mRNA. A subset of CD48 molecules is resistant to GPI-specific phospholipase C digestion and may exist in a complexed form on the cell surface. Immunoprecipitation, immunofluorescence, Northern blot, GPI-PLC digestion, Cos-7 transfection Journal of immunology (Baltimore, Md. : 1950) Medium 1848579
1999 Engagement of 2B4 on human NK cells by anti-2B4 mAb or by CD48 (its ligand) triggers NK cell-mediated cytotoxicity. 2B4 is also expressed on monocytes and basophils, but 2B4 ligation does not activate T cells or monocytes, indicating cell-type-specific signaling downstream of the 2B4–CD48 interaction. Cytotoxicity assays using anti-2B4 mAb and recombinant CD48 protein, flow cytometry, molecular cloning of human 2B4 European journal of immunology Medium 10359122
1999 CD48-deficient mice (generated by gene targeting) display a profound defect in CD4⁺ T cell activation: proliferative responses to mitogens, anti-CD3 mAb, and alloantigen are all reduced. CD48 is required on both T cells and antigen-presenting cells. The most dramatic impairment occurs when highly purified T cells are stimulated through the TCR plus PMA, suggesting CD48 plays a role in TCR signaling. Gene targeting (knockout mice), co-culture proliferation assays, mitogen and alloantigen stimulation assays Proceedings of the National Academy of Sciences of the United States of America High 9927686
1999 NAIL (human 2B4 homologue, later NTB-A) binds CD48 as its counter-receptor. Recombinant CD48 protein enhances NK cell cytotoxicity and induces IFN-γ production. Soluble NAIL-Fc stimulates B cell proliferation and DC IL-12/TNF-α release, demonstrating that CD48–NAIL/2B4 interactions regulate multiple immune cell responses. Soluble fusion protein binding assays, NK cytotoxicity assays, IFN-γ ELISA, B cell proliferation, DC cytokine assays European journal of immunology Medium 10556801
2000 CD48 co-clusters with IL-2Rα and HLA molecules in cholesterol-dependent lipid raft microdomains (~600–800 nm clusters) on T lymphoma cells. Disruption of membrane cholesterol with filipin or methyl-β-cyclodextrin disperses these clusters, whereas the transferrin receptor (non-raft) clusters are largely unaffected and do not co-localize with CD48. Immunogold staining/electron microscopy, confocal microscopy, cholesterol depletion, crosscorrelation analysis Proceedings of the National Academy of Sciences of the United States of America Medium 10823948
2002 Direct force measurements using surface force apparatus confirmed that the full-length extracellular domains of CD2 and CD48 adhere in a head-to-head orientation, with no long-range electrostatic attraction, abrupt adhesive failure (no partial unfolding), and weak adhesion requiring lateral receptor mobility. This is the first direct measurement of forces governing CD2–CD48 heterotypic adhesion. Direct surface force measurements between protein-coated lipid bilayers Biochemistry Medium 12356317
2003 CD48 on mast cells aggregates at sites of Mycobacterium tuberculosis binding, and anti-CD48 antibodies inhibit histamine release triggered by mycobacteria, implicating CD48 as a receptor mediating mast cell recognition of and activation by M. tuberculosis. Confocal microscopy of CD48 aggregation at bacterial binding sites, anti-CD48 mAb inhibition of histamine release Journal of immunology (Baltimore, Md. : 1950) Medium 12759438
2005 Homotypic 2B4/CD48 interactions among NK cells are essential for IL-2-driven NK cell expansion, cytotoxicity, and IFN-γ secretion; CD2/CD48 interactions on NK cells are not required for these functions. 2B4-deficient but not CD2-deficient NK cells fail to clear syngeneic tumor cells in vivo. Defective 2B4/CD48 signaling correlates with impaired calcium signaling. GFP-tagged 2B4 localizes specifically to NK–NK conjugation sites, confirming homotypic trans-interaction. Gene-deficient NK cells (2B4⁻/⁻, CD48⁻/⁻), cytotoxicity assays, IFN-γ ELISA, calcium imaging, GFP-2B4 live-cell imaging, in vivo tumor clearance Blood High 15905190
2005 Site-directed mutagenesis of human 2B4 identified Lys68 and Glu70 in the V domain as critical residues for CD48 binding and for 2B4-mediated functional activation of human NK cells; double Lys68Ala/Glu70Ala mutant abolishes CD48-Fc binding and NK activation. Site-directed mutagenesis, flow cytometry binding assay with CD48-Fc fusion protein, NK cell functional activation assay Journal of immunology (Baltimore, Md. : 1950) Medium 16002700
2006 Crystal structure of the receptor-binding domain of rat CD48 resolved. The receptor-binding surface is unusually flat and electrostatically complementary to CD2. Thermodynamic analysis showed CD48–CD2 binding is driven by equivalent weak enthalpic and entropic contributions, distinct from the human CD2–CD58 interaction (which has a large entropic barrier). The flat, charge-complementary topology explains why CD48 can cross-react with both CD2 and 2B4/CD244. X-ray crystallography, isothermal titration calorimetry/thermodynamic binding analysis, comparative structural modelling The Journal of biological chemistry High 16803907
2006 CD48 is an IL-3-inducible activating receptor on human eosinophils; cross-linking CD48 triggers release of eosinophil granule proteins (degranulation). In a murine asthma model, CD48 expression is induced by allergen challenge and partially regulated by IL-3; anti-IL-3 reduces both CD48 expression and airway inflammation. Flow cytometry, antibody cross-linking degranulation assays, murine OVA asthma model, anti-IL-3 antibody treatment Journal of immunology (Baltimore, Md. : 1950) Medium 16785501
2006 CD48 controls both T cell and APC function in experimental colitis. CD48⁻/⁻ CD4⁺ T cells fail to induce colitis when transferred into CD48⁻/⁻ × Rag-2⁻/⁻ recipients (but can into Rag-2⁻/⁻ hosts), indicating CD48 is required on APCs in the recipient to drive disease. CD48⁻/⁻ macrophages produce less TNF-α and IL-12 upon LPS stimulation and show defective bacterial clearance. Anti-CD48 mAb treatment ameliorates colitis even after disease onset. Adoptive transfer colitis model using CD48⁻/⁻ and Rag-2⁻/⁻ mice, in vitro macrophage stimulation assays, anti-CD48 therapeutic treatment Gastroenterology High 16472597
2009 GPI-anchored CD48 (but not CD59) is recruited to the immobilized TCR/CD3 complex upon T cell activation. CD48 reorganization is required for LAT association with the TCR/CD3 complex and for IL-2 production. CD2 acts upstream of CD48: CD2 associates with TCR/CD3 independently of CD48 and recruits Lck, while CD48 recruitment and subsequent LAT association depend on CD2. Thus CD2 and CD48 cooperate hierarchically to build the early TCR signalosome. Co-immunoprecipitation, proximity ligation/signalosome reconstitution assays, CD48 knockdown/knockout T cells, IL-2 ELISA, LAT co-precipitation Journal of immunology (Baltimore, Md. : 1950) High 19494291
1997 Both type I (α/β) and type II (γ) interferons upregulate CD48 mRNA and surface protein expression on multiple human cell lines and peripheral blood CD3⁺, CD14⁺, and CD19⁺ subsets; IFN has no corresponding effect on LFA-3 expression. Northern blot, flow cytometry, IFN treatment of human cell lines and PBMCs Journal of interferon & cytokine research Medium 9041467
2013 ORMDL3, an ER-localized protein, regulates IL-3-induced CD48 expression on eosinophils and mediates CD48-dependent eosinophil degranulation; ORMDL3 knockdown significantly inhibits eosinophil degranulation and in vivo recruitment. ORMDL3 overexpression and siRNA knockdown in eosinophils, flow cytometry, in vivo murine asthma model, degranulation assays Nature communications Medium 24056518
2014 CD48 on human and murine eosinophils serves as a receptor mediating Staphylococcus aureus and its exotoxins (SEB, protein A, peptidoglycan) activation: SA/exotoxins physically bind to CD48, cause eosinophil degranulation, cytokine release, and signal transduction; these effects are significantly reduced by CD48 blocking or in CD48⁻/⁻ bone marrow eosinophils. In vivo, CD48⁻/⁻ mice show reduced eosinophil recruitment in SEB-induced peritonitis. Confocal microscopy of SA binding to CD48, adhesion and degranulation assays, cytokine ELISA, CD48⁻/⁻ mouse peritonitis model Clinical and experimental allergy High 25255823
2014 Engagement of SLAMF2/CD48 on dendritic cells (DCs) by SLAMF4 recombinant protein or anti-SLAMF2 Ab activates immature DCs and prolongs survival of DNA-activated DCs by inhibiting IFN-β production and IFN-β-induced apoptosis, and by promoting production of the granzyme B inhibitor protease inhibitor-9. Anti-SLAMF2 mAb and recombinant SLAMF4 protein engagement of DCs, IFN-β ELISA, apoptosis assays, granzyme B inhibitor measurement Journal of immunology (Baltimore, Md. : 1950) Medium 24670806
2016 2B4 on NK cells interacts with CD48 both in trans (on neighbouring cells) and in cis (on the same NK cell surface), using the same binding site. Cis interaction induces basal 2B4 phosphorylation but reduces trans-binding to CD48-positive target cells; interfering with cis interaction enhanced lysis of CD48-expressing tumour cells. Proximity ligation assay, FRET, anti-2B4 blocking to perturb cis interaction, cytotoxicity assays Open biology Medium 27249817
2019 A cytomegalovirus-encoded soluble CD48 homologue (A43, encoded by owl monkey CMV) is secreted after proteolytic processing and binds human 2B4 with high affinity and slow dissociation rate (SPR). A43 abrogates host CD48:2B4 interactions, reduces NK–target conjugate formation and immunological synapse establishment, and impairs 2B4-mediated cytotoxicity and IFN-γ production by NK cells. Surface plasmon resonance, NK cell cytotoxicity assays, conjugate formation assays, immunological synapse imaging, IFN-γ ELISA PLoS pathogens High 30947296
2020 CD48 expression in AML cells is epigenetically regulated by DNA methylation; treatment with a hypomethylating agent increases CD48 expression on AML cells and enhances NK cell killing of AML cells in vitro. Restoration of CD48 expression reverses AML immune evasion and activates NK cell function in vivo. Methylation analysis, hypomethylating agent treatment, NK cytotoxicity assays in vitro and in vivo mouse model Clinical science (London, England : 1979) Medium 31922199
2020 Human innate lymphoid cell precursors (ILCPs) express CD48, and the interaction of 2B4 (on NKPs) with CD48 (on ILCPs) promotes differentiation of ILC2s; 2B4–CD48 signaling modulates ILC lineage commitment. Flow cytometry of precursor subsets, in vitro differentiation assays, in vivo humanized mouse model Science immunology Medium 33219153
2021 GDF15 binds CD48 as a previously unrecognized receptor on T cells, thereby downregulating STUB1 (an E3 ubiquitin ligase that mediates FOXP3 degradation), which promotes generation of peripheral iTreg cells and enhances suppressive function of nTreg cells; GDF15 neutralizing antibody eradicates HCC in mouse models. Co-immunoprecipitation, mass spectrometry, RNA sequencing, ChIP, flow cytometry (CyTOF), GDF15-knockout HCC mouse model, hybridoma-generated neutralizing mAb Journal for immunotherapy of cancer Medium 34489334
2022 Genome-wide CRISPR screens in ATLL cell lines identified CD48 as the top gene whose knockout confers resistance to NK-cell-mediated cytotoxicity; CD48-knockout ATLL cells evade NK-cell effector function (reduced IFN-γ induction and degranulation by primary human NK cells). Primary ATLL cells show reduced CD48 expression with disease progression. Genome-wide CRISPR knockout screen, flow cytometry, NK cytotoxicity assays with primary human NK cells Blood High 35921533
2024 KDM6A loss leads to increased H3K27me3 on the CD48 promoter, causing CD48 downregulation in multiple myeloma cells. EZH2 inhibitor treatment restores CD48 (and CD38) expression and reverses resistance to Daratumumab-mediated ADCC, establishing KDM6A/EZH2/H3K27me3 as an epigenetic axis regulating CD48 expression. Genome-wide CRISPR screens, ChIP for H3K27me3 on CD48 promoter, EZH2 inhibitor treatment, CD38/CD48 re-expression, ADCC assays Nature communications High 38355622

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 53770 9254694
2009 BLAST+: architecture and applications. BMC bioinformatics 15253 20003500
2002 BLAT--the BLAST-like alignment tool. Genome research 6510 11932250
2012 Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Science translational medicine 765 22593173
2012 Domain enhanced lookup time accelerated BLAST. Biology direct 628 22510480
2004 The biology of CML blast crisis. Blood 423 14982876
1981 A nuclear antigen associated with cell proliferation and blast transformation. The Journal of experimental medicine 350 6172535
1998 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48. The Journal of experimental medicine 328 9841922
2006 A B-lectin receptor kinase gene conferring rice blast resistance. The Plant journal : for cell and molecular biology 294 16709195
1992 CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. The Journal of experimental medicine 247 1383383
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 137 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 125 32367535
2022 Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood 123 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
1993 Affinity and kinetic analysis of the interaction of the cell adhesion molecules rat CD2 and CD48. The EMBO journal 114 7903240
2019 RRM Transcription Factors Interact with NLRs and Regulate Broad-Spectrum Blast Resistance in Rice. Molecular cell 106 30975460
2007 Susceptibility of rice to the blast fungus, Magnaporthe grisea. Journal of plant physiology 105 17905473
1990 Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3. The Journal of experimental medicine 103 1693656
2016 Immunity to Rice Blast Disease by Suppression of Effector-Triggered Necrosis. Current biology : CB 99 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
1991 Expression of the Blast-1 activation/adhesion molecule and its identification as CD48. Journal of immunology (Baltimore, Md. : 1950) 91 1848579
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 86 31513573
2000 Using BLAST for identifying gene and protein names in journal articles. Gene 86 11163982
2014 EC-BLAST: a tool to automatically search and compare enzyme reactions. Nature methods 85 24412978
2023 UniProt Tools: BLAST, Align, Peptide Search, and ID Mapping. Current protocols 84 36943033
1999 Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48. European journal of immunology 81 10556801
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
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
2016 Management of CML-blast crisis. Best practice & research. Clinical haematology 58 27839570
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
2007 PSI-BLAST tutorial. Methods in molecular biology (Clifton, N.J.) 50 17993673
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
1996 NMR analysis of interacting soluble forms of the cell-cell recognition molecules CD2 and CD48. Biochemistry 46 8634239
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 43 36952381
2018 Osmotic stabilization prevents cochlear synaptopathy after blast trauma. Proceedings of the National Academy of Sciences of the United States of America 42 29735658
2014 Hippocampal vulnerability and subacute response following varied blast magnitudes. Neuroscience letters 40 24726403
2011 CD48 as a novel molecular target for antibody therapy in multiple myeloma. British journal of haematology 40 22098460
2009 Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome. Journal of immunology (Baltimore, Md. : 1950) 40 19494291
2007 CD48 is critically involved in allergic eosinophilic airway inflammation. American journal of respiratory and critical care medicine 40 17290046
2018 Blast-induced "PTSD": Evidence from an animal model. Neuropharmacology 37 30227150
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
2015 OsGF14b Positively Regulates Panicle Blast Resistance but Negatively Regulates Leaf Blast Resistance in Rice. Molecular plant-microbe interactions : MPMI 35 26467468
2014 The CD48 receptor mediates Staphylococcus aureus human and murine eosinophil activation. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 35 25255823
2021 Tangeretin inhibits fungal ferroptosis to suppress rice blast. Journal of integrative plant biology 34 34570416
2005 2B4/CD48-mediated regulation of lymphocyte activation and function. Journal of immunology (Baltimore, Md. : 1950) 34 16081768
2005 Pathobiology of lymphoid and myeloid blast crisis and management issues. Hematology. American Society of Hematology. Education Program 34 16304379
1995 Physical and genetic linkage of the genes encoding Ly-9 and CD48 on mouse and human chromosomes 1. Immunogenetics 34 7797269
2015 Confirmation of Pig-a mutation in flow cytometry-identified CD48-deficient T-lymphocytes from F344 rats. Mutagenesis 32 25820172
2022 Perspectives on Primary Blast Injury of the Brain: Translational Insights Into Non-inertial Low-Intensity Blast Injury. Frontiers in neurology 29 35095749
2022 Genome-wide CRISPR screens identify CD48 defining susceptibility to NK cytotoxicity in peripheral T-cell lymphomas. Blood 29 35921533
2024 Epigenetic regulation of CD38/CD48 by KDM6A mediates NK cell response in multiple myeloma. Nature communications 28 38355622
2006 Crystal structure and binding properties of the CD2 and CD244 (2B4)-binding protein, CD48. The Journal of biological chemistry 28 16803907
2006 CD48 controls T-cell and antigen-presenting cell functions in experimental colitis. Gastroenterology 27 16472597
2020 Acute myeloid leukemia immune escape by epigenetic CD48 silencing. Clinical science (London, England : 1979) 25 31922199
2016 CD48 on blood leukocytes and in serum of asthma patients varies with severity. Allergy 25 27859399
2015 Blast induced neurotrauma causes overpressure dependent changes to the DNA methylation equilibrium. Neuroscience letters 25 26232681
2005 Distinctive lack of CD48 expression in subsets of human dendritic cells tunes NK cell activation. Journal of immunology (Baltimore, Md. : 1950) 25 16148114
2021 Blast and accelerated phase CML: room for improvement. Hematology. American Society of Hematology. Education Program 24 34889372
2019 Cellular Dynamics and Genomic Identity of Centromeres in Cereal Blast Fungus. mBio 24 31363034
2010 SHIP influences signals from CD48 and MHC class I ligands that regulate NK cell homeostasis, effector function, and repertoire formation. Journal of immunology (Baltimore, Md. : 1950) 24 20363967
2022 Review of blast noise and the auditory system. Hearing research 23 35181171
2019 Blast Preconditioning Protects Retinal Ganglion Cells and Reveals Targets for Prevention of Neurodegeneration Following Blast-Mediated Traumatic Brian Injury. Investigative ophthalmology & visual science 23 31598627
2014 HTLV-1 specific CD8+ T cell function augmented by blockade of 2B4/CD48 interaction in HTLV-1 infection. PloS one 22 24505299
2011 The SLAM family member CD48 (Slamf2) protects lupus-prone mice from autoimmune nephritis. Journal of autoimmunity 22 21561736
2005 Mutational analysis of the human 2B4 (CD244)/CD48 interaction: Lys68 and Glu70 in the V domain of 2B4 are critical for CD48 binding and functional activation of NK cells. Journal of immunology (Baltimore, Md. : 1950) 22 16002700
1997 Characterisation of the low affinity interaction between rat cell adhesion molecules CD2 and CD48 by analytical ultracentrifugation. European biophysics journal : EBJ 22 9188168
2024 Phytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice blast. Nature communications 21 38653755
2021 NK1 antagonists attenuate tau phosphorylation after blast and repeated concussive injury. Scientific reports 21 33893374
2018 Vestibular Injury After Low-Intensity Blast Exposure. Frontiers in neurology 21 29867715
2011 Auto-antibody production and glomerulonephritis in congenic Slamf1-/- and Slamf2-/- [B6.129] but not in Slamf1-/- and Slamf2-/- [BALB/c.129] mice. International immunology 21 21278219
1996 CD48 delivers an accessory signal for CD40-mediated activation of human B cells. Cellular immunology 21 8929458
1991 Further evidence for a gamma/delta T cell receptor-mediated TCT.1/CD48 recognition. Journal of immunology (Baltimore, Md. : 1950) 21 1655899
2002 Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48. Biochemistry 20 12356317
1998 Enhanced murine CD4+ T cell responses induced by the CD2 ligand CD48. European journal of immunology 20 9862369
2021 SMI-BLAST: a novel supervised search framework based on PSI-BLAST for protein remote homology detection. Bioinformatics (Oxford, England) 19 32898222
2020 Human innate lymphoid cell precursors express CD48 that modulates ILC differentiation through 2B4 signaling. Science immunology 19 33219153
2017 The Effects of Blast Exposure on Protein Deimination in the Brain. Oxidative medicine and cellular longevity 19 28626499
2016 Modulation of natural killer cell functions by interactions between 2B4 and CD48 in cis and in trans. Open biology 19 27249817
2013 Toward a "structural BLAST": using structural relationships to infer function. Protein science : a publication of the Protein Society 19 23349097
1997 Both human alpha/beta and gamma interferons upregulate the expression of CD48 cell surface molecules. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 19 9041467
2023 Is Protein BLAST a thing of the past? Nature communications 17 38081865
2021 Axonopathy precedes cell death in ocular damage mediated by blast exposure. Scientific reports 17 34083587
2019 Subversion of natural killer cell responses by a cytomegalovirus-encoded soluble CD48 decoy receptor. PLoS pathogens 17 30947296
2014 Engagement of SLAMF2/CD48 prolongs the time frame of effective T cell activation by supporting mature dendritic cell survival. Journal of immunology (Baltimore, Md. : 1950) 17 24670806
2005 Clinical implications of blast immunophenotypes in myelodysplastic syndromes. Leukemia & lymphoma 17 16109603

Missed literature

Know a paper Affinage missed for CD48? Flag it for the maintainers and the community.

No submissions yet.