Affinage

CD244

Natural killer cell receptor 2B4 · UniProt Q9BZW8

Length
370 aa
Mass
41.6 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD244 (2B4) is a SLAM-family immunoreceptor that binds CD48 and functions as a context-dependent activating or inhibitory receptor across NK cells, T cells, eosinophils, mast cells, dendritic cells, and macrophages, governing cytotoxicity, cytokine production, phagocytosis, and immune self-tolerance. When the adaptor SAP is present, CD244 engagement recruits FynT via cytoplasmic TxYxxV/I motifs, triggering phosphorylation of Vav-1, SHIP-1/c-Cbl, and Ras/MAPK (ERK, p38) and PLC-γ1 cascades that drive NK cell killing and IFN-γ secretion; when SAP is absent—as in X-linked lymphoproliferative disease (XLP1)—or when CD244 expression is high, the receptor instead recruits SH2-containing phosphatases, competes with CD2 for CD48 binding, and blocks actin-dependent lipid raft recruitment, converting it to an inhibitory receptor (PMID:15169881, PMID:18523281, PMID:12515815, PMID:19586919, PMID:28386908). Beyond classical lymphocyte regulation, CD244 on macrophages acts as a "don't eat me" signal that suppresses LRP1/mTOR/Syk-mediated phagocytosis independently of CD47, and inhibits anti-tumorigenic macrophage differentiation by suppressing autophagy pathways (PMID:35061505, PMID:38424542). CD244 also epigenetically represses IFN-γ and TNF-α in CD8+ T cells during tuberculosis infection by inducing lncRNA-CD244, which recruits EZH2 to install H3K27me3 at cytokine promoters (PMID:26150504).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1998 High

    Identifying CD48 as the counter-receptor for 2B4 established the receptor-ligand pair that anchors all subsequent signaling studies of the CD244 axis.

    Evidence CD48-IgG1 fusion protein binding to 2B4-expressing cells detected by immunofluorescence and immunoprecipitation

    PMID:9834056

    Open questions at the time
    • Binding affinity and stoichiometry not quantified
    • Whether 2B4 binds any other ligands was untested
  2. 1999 High

    Functional cross-linking demonstrated that 2B4 engagement triggers NK cytotoxicity, establishing CD244 as an activating receptor and defining its broad expression on NK cells, CD8+ T cells, monocytes, and basophils.

    Evidence Redirected killing assays and antibody cross-linking on primary human NK cells

    PMID:10359122

    Open questions at the time
    • Intracellular signaling pathway unknown
    • Mechanism of activation versus co-stimulation not resolved
  3. 2000 High

    Demonstration that 2B4 requires co-engagement with NKp46 to trigger killing, and that SAP-deficient XLP patients lack 2B4-mediated cytotoxicity, reframed CD244 as a co-stimulatory receptor and placed SAP as an essential signaling adaptor.

    Evidence Redirected killing with NKp46 modulation; NK cytotoxicity assays on XLP patient cells

    PMID:10741393 PMID:11093147

    Open questions at the time
    • How SAP couples to 2B4 biochemically was undefined
    • Whether 2B4 can ever function as a primary activating receptor remained debatable
  4. 2001 Medium

    Characterization of the cytoplasmic TxYxxV/I motifs as SAP-binding sites and identification of downstream Ras/MAPK (ERK, p38) signaling with constitutive LAT association defined the proximal signaling architecture of activating 2B4.

    Evidence Sequence/domain analysis, co-immunoprecipitation of LAT, pharmacological MAPK inhibitors, AP-1 DNA-binding assays

    PMID:11513145 PMID:11714782

    Open questions at the time
    • Direct kinase responsible for 2B4 phosphorylation not identified
    • LAT association not confirmed by reciprocal IP or mutagenesis
  5. 2003 High

    Discovering that phosphorylated 2B4 localizes exclusively to lipid rafts in an actin-dependent manner, and that inhibitory receptors block this relocalization, revealed a spatial gating mechanism controlling 2B4 activation.

    Evidence Detergent-resistant membrane fractionation, actin depolymerization drugs, inhibitory receptor co-engagement on NK cells

    PMID:12515815

    Open questions at the time
    • Identity of the inhibitory receptor-associated phosphatase that prevents raft recruitment unknown
    • Whether raft exclusion is the sole inhibitory mechanism was unclear
  6. 2004 High

    Structure–function mutagenesis showed that SAP recruits FynT to 2B4 via SAP Arg78, and that this complex phosphorylates Vav-1, SHIP-1, and c-Cbl, completing the proximal activating signaling cascade.

    Evidence Mutagenesis of cytoplasmic tyrosines and SAP Arg78, co-immunoprecipitation of FynT, phosphorylation assays in NK cells

    PMID:15169881

    Open questions at the time
    • Relative contribution of each tyrosine motif to different downstream effectors unresolved
    • Whether additional kinases substitute for FynT unknown
  7. 2005 High

    Genetic knockout studies revealed a dual role for CD244: homotypic 2B4/CD48 interactions among NK cells are required for IL-2-driven expansion and effector function, yet 2B4 also maintains NK self-tolerance by inhibiting lysis of syngeneic targets through a non-MHC-I mechanism.

    Evidence 2B4-deficient and β2m-deficient mice, in vivo bone marrow rejection, GFP-tagged 2B4 live imaging at NK-NK conjugates, calcium flux assays

    PMID:15870174 PMID:15905190

    Open questions at the time
    • How the same receptor switches between activating and inhibitory modes in vivo was unexplained
    • Whether SAP expression levels differ between activating and tolerogenic contexts untested
  8. 2007 High

    Establishing that 2B4/CD48 signaling prevents perforin-dependent NK cell fratricide demonstrated a critical survival function for CD244 in maintaining the NK cell compartment.

    Evidence 2B4-deficient, CD48-deficient, and perforin-deficient mice with in vivo fratricide assays

    PMID:17537992

    Open questions at the time
    • Whether fratricide prevention requires SAP or is SAP-independent was not tested
    • Relevance to human NK homeostasis not demonstrated
  9. 2008 High

    Systematic variation of 2B4 expression level, cross-linking intensity, and SAP availability resolved the activating-versus-inhibitory paradox: high 2B4 expression with SAP paucity produces inhibition, while moderate expression with SAP sufficiency produces activation.

    Evidence Controlled expression systems with titrated cross-linking and SAP knockdown/overexpression, cytotoxicity assays

    PMID:18523281

    Open questions at the time
    • Quantitative threshold of SAP:2B4 ratio governing the switch undefined
    • In vivo validation of the dose-response model lacking
  10. 2009 High

    Discovery that mouse CD244 inhibitory function involves competition with CD2 for CD48 and that EAT-2 recruits PLC-γ1 via its phosphotyrosine revealed a SAP-independent inhibitory signaling arm through which CD244 modulates co-receptor access.

    Evidence Mutagenesis of proline-rich and tyrosine motifs in EAT-2, T cell hybridoma assays, biochemical PLC-γ1 recruitment analysis

    PMID:19586919

    Open questions at the time
    • Whether EAT-2/PLC-γ1 pathway operates in human cells not shown
    • Relative contribution of CD2 competition versus phosphatase recruitment to net inhibition unknown
  11. 2010 High

    In vivo LCMV infection showed that 2B4 on NK cells provides tolerance to activated CD8+ T cells, preventing their perforin-dependent lysis and enabling effective antiviral T cell responses.

    Evidence 2B4-deficient mice infected with LCMV, bone marrow chimeras, perforin-dependent killing measurements

    PMID:20440077

    Open questions at the time
    • Whether this tolerance mechanism extends to other viral infections untested
    • Signaling pathway mediating tolerance in this context not dissected
  12. 2011 High

    CD244 deficiency on a non-autoimmune B6 background caused spontaneous T/B cell activation, increased T follicular helper cells, and autoantibody production—an NK-independent phenotype—revealing CD244 as a negative regulator of adaptive immune autoreactivity.

    Evidence CD244-deficient mice with NK depletion, lupus transfer model, autoantibody detection

    PMID:21622868

    Open questions at the time
    • Mechanism by which CD244 restrains T follicular helper cells unknown
    • Whether intrinsic T or B cell CD244 expression is responsible not resolved
  13. 2015 High

    CD244 signaling was linked to epigenetic repression in CD8+ T cells during TB: it drives expression of lncRNA-CD244, which recruits EZH2 to IFN-γ and TNF-α promoters to install H3K27me3, establishing a chromatin-based mechanism for CD244-mediated immune suppression.

    Evidence ChIP for H3K27me3 and EZH2, lncRNA knockdown, adoptive transfer into MTB-infected mice

    PMID:26150504

    Open questions at the time
    • How CD244 signaling induces lncRNA-CD244 transcription mechanistically undefined
    • Whether this epigenetic pathway operates outside the TB context unknown
  14. 2017 High

    Demonstration that gut bacterial products induce SLAMF4 expression on intestinal immune cells and that SLAMF4-deficient mice are more susceptible to oral pathogens extended CD244 function to mucosal immunity.

    Evidence Gnotobiotic mice, GFP bone marrow chimeras, oral infection models

    PMID:28341747

    Open questions at the time
    • Specific bacterial products or PRR pathways inducing CD244 not identified
    • Whether CD244 acts on epithelial versus immune cells in the gut unclear
  15. 2022 High

    CD244 was identified as a phagocytic checkpoint ('don't eat me' signal) on macrophages that suppresses LRP1/mTOR/Syk eat-me signaling through SH2-containing phosphatases, operating independently of the CD47-SIRPα axis.

    Evidence SLAMF3/4-deficient mice, bone marrow transplant rejection assays, LRP1/mTOR/Syk pathway analysis, HLH patient samples

    PMID:35061505

    Open questions at the time
    • Whether therapeutic CD244 blockade synergizes with anti-CD47 in vivo not tested
    • Specific SH2-phosphatase identity (SHP-1 vs SHP-2) not resolved
  16. 2024 High

    Monocyte-specific CD244 deletion revealed that CD244 inhibits anti-tumorigenic macrophage differentiation, phagocytosis, and MHC-I antigen presentation by suppressing autophagy, and that ER stress upregulates CD244 on monocytes, linking tumor microenvironment stress to myeloid immune evasion.

    Evidence CD244fl/fl LysMcre conditional KO mice, scRNA-seq, autophagy pathway analysis, tumor models with anti-PD-L1 combination

    PMID:38424542

    Open questions at the time
    • Molecular link between CD244 signaling and autophagy suppression not fully delineated
    • Whether ER stress-induced CD244 upregulation is transcriptional or post-transcriptional unclear
    • Human relevance of monocyte-specific findings not validated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for CD244's dual activating/inhibitory signaling, the quantitative SAP:2B4 threshold governing signal polarity, and whether combined targeting of CD244 and CD47 on macrophages achieves synergistic anti-tumor phagocytosis.
  • No crystal structure of CD244 cytoplasmic domain with SAP/EAT-2 available
  • In vivo quantitation of SAP:2B4 ratios across cell types lacking
  • Therapeutic antibody or genetic studies combining CD244 and CD47 blockade not reported

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 6
Pathway
R-HSA-168256 Immune System 7 R-HSA-5357801 Programmed Cell Death 2 R-HSA-9612973 Autophagy 1
Partners
CD48EAT2FYNLATPLCG1SH2D1AVAV1

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 2B4 (CD244) was identified as a counter-receptor (ligand) for CD48 using a chimeric CD48-IgG1 fusion protein in immunofluorescence and immunoprecipitation experiments. Immunofluorescence and immunoprecipitation with CD48-IgG1 fusion protein Journal of immunology High 9834056
1999 Human 2B4 is expressed on NK cells, CD8+ T cells, monocytes, and basophils; engagement of 2B4 with anti-2B4 antibody or CD48 triggers NK cell-mediated cytotoxicity, establishing 2B4 as an activating receptor on NK cells. Redirected killing assay, monoclonal antibody cross-linking, cell surface biochemistry European journal of immunology High 10359122
2000 2B4 functions as a co-receptor in human NK cell activation; its activating function requires co-engagement of the triggering receptor NKp46, demonstrating that 2B4 acts as a co-stimulatory rather than primary activating receptor. Redirected killing assay with NK cell clones, antibody-mediated modulation of NKp46 European journal of immunology High 10741393
2000 XLPD patients lacking SAP have a specific defect in 2B4-mediated NK cell cytotoxicity, placing SAP as an essential adaptor for 2B4 signaling and linking 2B4 dysfunction to XLP pathogenesis. NK cell cytotoxicity assays in XLP patient cells European journal of immunology High 11093147
2000 Ligation of 2B4 on human NK cell line YT induces cytotoxicity, IFN-γ production, and upregulates matrix metalloproteinase-2 expression, while also downregulating surface 2B4 expression. NK cell line stimulation with anti-2B4 mAb, IFN-γ ELISA, cytotoxicity assays, MMP-2 expression analysis Immunology Medium 10929061
2001 The cytoplasmic domain of 2B4 contains unique TxYxxV/I tyrosine motifs that associate with the SH2 domain of SAP, the protein mutated in X-linked lymphoproliferative disease, linking 2B4 intracellular signaling to SAP. Sequence analysis, biochemical association studies Immunological reviews Medium 11513145
2001 2B4/CD48 interaction regulates CD8+ T cell proliferation; blocking 2B4 with antibody inhibited CD8+ T cell proliferation, and 2B4/CD48 interactions can occur directly between T cells without APCs. Antibody blocking of 2B4, proliferation assays with mixed T cell populations Journal of immunology Medium 11739483
2001 2B4-mediated activation of NK cell cytotoxicity involves Ras/Raf-dependent MAPK signaling (ERK1/2 and p38), while IFN-γ release specifically requires p38 and transcription, and 2B4 constitutively associates with the adaptor LAT. Pharmacological inhibitors, AP-1 DNA binding assays, co-immunoprecipitation of LAT Journal of immunology Medium 11714782
2003 Inhibitory NK receptors block 2B4 phosphorylation by preventing its actin cytoskeleton-dependent recruitment into lipid rafts; phosphorylated 2B4 localizes exclusively to detergent-resistant membrane fractions, and both raft integrity and actin polymerization are required for 2B4 activating function. Detergent-resistant membrane fractionation, actin depolymerization, inhibitory receptor co-engagement assays The Journal of experimental medicine High 12515815
2004 2B4 engagement triggers tyrosine phosphorylation of 2B4 itself, Vav-1, and SHIP-1/c-Cbl through cytoplasmic tyrosine-based motifs; this signaling is absolutely dependent on SAP, which recruits FynT; mutation of SAP Arg78 (critical for SAP-FynT binding) eliminates 2B4-mediated phosphorylation. Structure-function mutagenesis of cytoplasmic tyrosines, co-immunoprecipitation of FynT, SAP Arg78 mutation, phosphorylation assays in NK cells Molecular and cellular biology High 15169881
2004 NK cells stimulate T cell and NK cell proliferation through 2B4 (on NK cells)/CD48 (on T or NK cells) interactions; homotypic NK-NK 2B4/CD48 interactions enhance IL-2-driven NK proliferation. Blocking antibody studies, co-culture proliferation assays with defined receptor-expressing cells Journal of immunology Medium 15210772
2005 2B4 inhibits NK cell lysis of syngeneic targets through a non-MHC class I mechanism; 2B4 and MHC class I inhibitory receptors act non-redundantly to maintain NK self-tolerance, demonstrated in beta2m-deficient mice and in vivo bone marrow rejection. 2B4-deficient mice, beta2m-deficient mice, in vivo bone marrow rejection assay Blood High 15870174
2005 Homotypic 2B4/CD48 interactions among NK cells are essential for IL-2-driven NK expansion, cytotoxicity, and IFN-γ secretion; GFP-tagged 2B4 localizes to NK-NK conjugation sites; impaired activation is accompanied by defective calcium signaling. 2B4-deficient mice, blocking antibodies, GFP-tagged 2B4 live imaging, calcium flux assays, tumor clearance in vivo Blood High 15905190
2005 2B4 expressed on human eosinophils is functional; cross-linking 2B4 on eosinophils triggers eosinophil peroxidase release, IFN-γ and IL-4 secretion, cytotoxicity against tumor cell lines, and ERK/tyrosine phosphorylation; eosinophils also express SAP. Flow cytometry, antibody cross-linking, cytotoxicity assays, ELISA, western blot for ERK phosphorylation Journal of immunology Medium 15611233
2006 2B4 can function as an activating NK cell ligand: 2B4-expressing target cells stimulate NK cytotoxicity and IFN-γ production through NK cell-expressed CD48; 2B4 does not bind other SLAM-related receptors, exclusively interacting with CD48. Soluble receptor fusion proteins, SRR-transfected cells, redirected lysis, blocking antibodies Journal of immunology High 16585556
2007 2B4/CD48 interaction inhibits NK cell fratricide; in the absence of 2B4-CD48 signaling, activated murine NK cells kill each other in a perforin-dependent manner both in vitro and in vivo. 2B4-deficient, CD48-deficient mice, perforin-deficient mice, blocking antibodies, in vivo fratricide assays Blood High 17537992
2008 The level of 2B4 expression and degree of 2B4 cross-linking determine whether 2B4 activates or inhibits NK cells: high expression and heavy cross-linking with paucity of SAP promote inhibitory function; both human and murine 2B4 can activate or inhibit NK cells depending on these parameters. Controlled expression systems, titrated cross-linking, SAP knockdown/overexpression, cytotoxicity assays Journal of immunology High 18523281
2009 CD244 inhibitory/activating functions depend on both CD2 and phospholipase C-γ1 (PLC-γ1); mouse CD244 inhibitory effects are mediated by competition with CD2 for CD48 at the cell surface; EAT-2 phosphorylated tyrosine motif recruits PLC-γ1 as a novel signaling mechanism; FYN kinase provides an intracellular link between CD2 and CD244. Mutagenesis of proline-rich and tyrosine motifs, T cell hybridoma activation assays, biochemical signaling analysis The Journal of biological chemistry High 19586919
2009 2B4 signaling domain acts as a co-stimulatory domain in human T cells when used in chimeric receptors; 2B4 alone fails to induce T cell effector functions but significantly augments TCRζ-mediated antigen-specific proliferation and activation. Retroviral chimeric receptor gene transfer, co-culture cytotoxicity and proliferation assays Cancer immunology, immunotherapy Medium 19360406
2010 TGF-β1 down-regulates 2B4 expression on NK cells along with its intracellular adaptor SAP, impairing NK cell cytotoxicity and IFN-γ production; anti-TGF-β1 antibodies restore 2B4 and NKG2D expression in vitro. In vitro TGF-β1 treatment, blocking antibodies, flow cytometry, functional assays in HBV patient samples PLoS pathogens Medium 22438812
2010 2B4 on NK cells provides self-tolerance to activated CD8+ T cells (CD44hi); in 2B4-deficient mice, NK cells lysed activated CD8+ T cells via perforin, leading to diminished LCMV-specific T cell responses and prolonged viral persistence. 2B4-deficient mice, LCMV infection model, bone marrow chimeras, perforin-dependent killing assays The Journal of clinical investigation High 20440077
2011 CD244 (Slamf4) deficiency in non-autoimmune-prone B6 mice leads to spontaneous development of activated T and B cells, increased T follicular helper cells, and autoantibody production; enhanced humoral autoimmunity in a lupus transfer model is NK cell-independent, establishing a negative regulatory role for CD244 in T and B cell-mediated autoimmunity. CD244-deficient mice, NK cell depletion, B6.C-H-2bm12 lupus transfer model, flow cytometry, autoantibody detection Journal of immunology High 21622868
2013 CD244 signaling in CD4+ T cells from active TB patients inhibits IFN-γ production; cross-linking CD244 significantly decreased IFN-γ production while blockade increased it, demonstrating an inhibitory role for CD244 signaling in antigen-specific CD4+ T cells. Anti-CD244 cross-linking, blocking antibody experiments, intracellular cytokine staining in patient T cells PloS one Medium 23638187
2013 CD244 undergoes rapid internalization to an acidic intracellular compartment upon simultaneous TCR and CD244 signaling; this two-signal mechanism for CD244 downmodulation requires TCR-proximal signaling and is not induced by PMA-ionomycin or inhibited by PI3K inhibition. pH-sensitive fluorophore-conjugated avidin-Ab tetramers, pharmacological inhibitors, flow cytometry on CD8 T cell clones Journal of immunology High 23913963
2014 2B4/CD244 up-regulation on antigen-specific CD8+ T cells induced by selective CD28 blockade (not CTLA-4-Ig) functionally contributes to inhibition of allograft-specific CD8+ T cell responses; 2B4 deficiency diminished the inhibitory impact of CD28 blockade. CD244-deficient mice, selective CD28 blockade, antigen-specific CD8+ T cell tracking in transplant model The Journal of experimental medicine High 24493803
2014 2B4 has complex inhibitory and stimulatory roles in mast cells and eosinophils: 2B4 inhibits mast cell degranulation but stimulates eosinophil migration; 2B4-deficient mice show overdegranulated MCs and reduced eosinophil infiltration in atopic dermatitis and peritonitis models. Bone marrow-derived MC cultures, 2B4-deficient mice, peritonitis and atopic dermatitis models, degranulation and migration assays The Journal of investigative dermatology High 24999594
2015 CD244 signaling drives expression of lncRNA-CD244 by maintaining permissive chromatin at its locus; lncRNA-CD244 then recruits EZH2 to IFN-γ and TNF-α promoters, inducing H3K27 trimethylation and repressive chromatin states, thereby inhibiting IFN-γ/TNF-α expression in CD8+ T cells during TB infection. ChIP for H3K27me3, EZH2 recruitment assays, lncRNA knockdown, adoptive transfer into MTB-infected mice PNAS High 26150504
2015 CD244 is expressed on all murine dendritic cell subsets and negatively regulates DC function; CD244-deficient DCs produce higher levels of pro-inflammatory cytokines upon TLR stimulation and elicit increased NK cell activation in vitro. CD244-deficient mice, TLR stimulation, cytokine measurement (Luminex), NK activation co-culture Immunology and cell biology Medium 25643613
2017 SLAMF4 (CD244) expression on intestinal immune cells is induced by gut bacterial products (particularly gut anaerobes) through gut-resident APCs directly in the intestinal mucosa; SLAMF4-deficient mice show increased susceptibility to oral pathogens, establishing a role in intestinal immune protection. GFP bone marrow chimeras, gnotobiotic mice, LTα and TNLG8A-deficient mice, oral infection models Gut High 28341747
2017 In XLP1 patients lacking SAP, 2B4 functions as an inhibitory receptor; the inhibitory 2B4/CD48 pathway prevents killing of CD48+ EBV-transformed B cells and M1 macrophages; this pathway also plays a role in NK cell education during maturation. XLP1 patient NK cells, KIR/KIR-L genotyping, cytotoxicity assays against CD48+ and CD48- targets European journal of immunology High 28386908
2020 The 2B4-expressing ILC precursor/progenitor compartment in humans: CD48 expressed on ILC precursors engages 2B4 on neighboring cells and modulates ILC differentiation; the interaction of 2B4 with CD48 specifically induced differentiation of ILC2s. In vitro differentiation assays from sorted progenitor populations, blocking of 2B4/CD48 interaction Science immunology Medium 33219153
2022 SLAMF4 (CD244) functions as a 'don't eat me' receptor on macrophages inhibiting phagocytosis of hematopoietic cells; SLAMF4 suppresses eat-me signals (LRP1-mediated mTOR and Syk activation) through SH2 domain-containing phosphatases; SLAMF4 acts independently of CD47 to restrict macrophage phagocytosis. SLAMF3/4-deficient mice, bone marrow transplant rejection assays, mechanistic analysis of LRP1/mTOR/Syk signaling, hemophagocytic lymphohistiocytosis patient samples Science immunology High 35061505
2024 CD244 on monocytes/macrophages impedes anti-tumorigenic macrophage (Ly6Clow) differentiation, phagocytosis, and MHC-I antigen presentation by suppressing autophagy pathways; ER stress increases CD244 expression on monocytes; monocyte-specific CD244 deletion (LysMcre) reduces tumor volume and enhances antigen-specific CD8 T cell responses. Monocyte-specific conditional KO (CD244fl/fl LysMcre), flow cytometry, scRNA-seq, autophagy pathway analysis, adoptive transfer with anti-PD-L1 combination Molecular cancer High 38424542

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Activating interactions in human NK cell recognition: the role of 2B4-CD48. European journal of immunology 208 10359122
2000 2B4 functions as a co-receptor in human NK cell activation. European journal of immunology 185 10741393
2010 The immunoregulatory role of CD244 in chronic hepatitis B infection and its inhibitory potential on virus-specific CD8+ T-cell function. Hepatology (Baltimore, Md.) 181 21064032
2015 Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T-cell immune responses in tuberculosis infection. Proceedings of the National Academy of Sciences of the United States of America 170 26150504
2012 TGF-β1 down-regulation of NKG2D/DAP10 and 2B4/SAP expression on human NK cells contributes to HBV persistence. PLoS pathogens 167 22438812
2009 Enthesitis: an autoinflammatory lesion linking nail and joint involvement in psoriatic disease. Journal of the European Academy of Dermatology and Venereology : JEADV 150 19686380
2000 Patients with X-linked lymphoproliferative disease have a defect in 2B4 receptor-mediated NK cell cytotoxicity. European journal of immunology 142 11093147
1998 Identification of the 2B4 molecule as a counter-receptor for CD48. Journal of immunology (Baltimore, Md. : 1950) 130 9834056
2008 Molecular basis of the dual functions of 2B4 (CD244). Journal of immunology (Baltimore, Md. : 1950) 122 18523281
2010 Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. The Journal of clinical investigation 120 20440077
2018 The Emerging Role of CD244 Signaling in Immune Cells of the Tumor Microenvironment. Frontiers in immunology 112 30546369
2001 2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes. Immunological reviews 109 11513145
2002 Nail-patella syndrome. Overview on clinical and molecular findings. Pediatric nephrology (Berlin, Germany) 101 12215822
2003 Natural killer cell inhibitory receptors block actin cytoskeleton-dependent recruitment of 2B4 (CD244) to lipid rafts. The Journal of experimental medicine 99 12515815
2008 Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population. Nature genetics 93 18794858
2005 2B4 (CD244) is a non-MHC binding receptor with multiple functions on natural killer cells and CD8+ T cells. Molecular immunology 89 15607804
2005 2B4 (CD244) is expressed and functional on human eosinophils. Journal of immunology (Baltimore, Md. : 1950) 87 15611233
2004 Molecular dissection of 2B4 signaling: implications for signal transduction by SLAM-related receptors. Molecular and cellular biology 86 15169881
2004 NK cells stimulate proliferation of T and NK cells through 2B4/CD48 interactions. Journal of immunology (Baltimore, Md. : 1950) 83 15210772
1999 Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4. Tissue antigens 80 10458320
1997 Cosegregation of open-angle glaucoma and the nail-patella syndrome. American journal of ophthalmology 79 9323941
2001 2B4 (CD244)-mediated activation of cytotoxicity and IFN-gamma release in human NK cells involves distinct pathways. Journal of immunology (Baltimore, Md. : 1950) 78 11714782
2000 LMX1B transactivation and expression in nail-patella syndrome. Human molecular genetics 78 10767331
2005 Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood 75 15905190
2021 Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases. Frontiers in immunology 68 33841431
1992 Mohs micrographic surgery of the nail unit. The Journal of dermatologic surgery and oncology 67 1644945
2008 Kidney disease in nail-patella syndrome. Pediatric nephrology (Berlin, Germany) 66 18535845
2012 Nail psoriasis: a review. American journal of clinical dermatology 62 22784035
2020 Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer. Cancers 61 32630303
2014 2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses. The Journal of experimental medicine 60 24493803
2010 Pigmented lesions of the nail unit: clinical and histopathologic features. Seminars in cutaneous medicine and surgery 60 21051008
2001 Metastatic tumors to the nail unit: subungual metastases. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.] 58 11277898
2022 SLAMF3 and SLAMF4 are immune checkpoints that constrain macrophage phagocytosis of hematopoietic tumors. Science immunology 57 35061505
2010 The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation. The Journal of investigative dermatology 57 21191399
2001 Cutting edge: Regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions. Journal of immunology (Baltimore, Md. : 1950) 57 11739483
2001 Yellow nail syndrome: does protein leakage play a role? The European respiratory journal 56 11307745
2020 NAIL: an evolutionarily conserved lncRNA essential for licensing coordinated activation of p38 and NFκB in colitis. Gut 55 33239342
2006 CD48 stimulation by 2B4 (CD244)-expressing targets activates human NK cells. Journal of immunology (Baltimore, Md. : 1950) 51 16585556
2011 Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia. American journal of human genetics 50 21665003
2020 CD244 represents a new therapeutic target in head and neck squamous cell carcinoma. Journal for immunotherapy of cancer 49 32217758
2014 Characteristics of patients with yellow nail syndrome and pleural effusion. Respirology (Carlton, Vic.) 47 25123563
2006 2B4 (CD244), NTB-A and CRACC (CS1) stimulate cytotoxicity but no proliferation in human NK cells. International immunology 47 16410313
1993 Trichohyalin: a structural protein of hair, tongue, nail, and epidermis. The Journal of investigative dermatology 47 7686953
1993 A bacterially expressed single-chain Fv construct from the 2B4 T-cell receptor. Proceedings of the National Academy of Sciences of the United States of America 47 8387198
2013 Drug-related nail disease. Clinics in dermatology 45 24079591
2011 DNA from keratinous tissue. Part I: hair and nail. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 45 21530205
2007 Expression of follicular sheath keratins in the normal nail with special reference to the morphological analysis of the distal nail unit. The American Journal of dermatopathology 45 18032949
2000 2B4 stimulation of YT cells induces natural killer cell cytolytic function and invasiveness. Immunology 45 10929061
2019 KDM4B: A Nail for Every Hammer? Genes 44 30759871
2005 2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice. Blood 42 15870174
2013 Nail tumors. Clinics in dermatology 41 24079590
1997 Fine mapping of the nail-patella syndrome locus at 9q34. American journal of human genetics 41 8981956
2008 Regulation of NK cell activity by 2B4, NTB-A and CRACC. Frontiers in bioscience : a journal and virtual library 40 17981603
2013 Comparative anatomy of mouse and human nail units. Anatomical record (Hoboken, N.J. : 2007) 38 23408541
2003 In vivo expression of putative LMX1B targets in nail-patella syndrome kidneys. The American journal of pathology 38 12819019
2011 Onychomatricoma in the light of the microanatomy of the normal nail unit. The American Journal of dermatopathology 37 21358379
2009 2B4 (CD244) signaling via chimeric receptors costimulates tumor-antigen specific proliferation and in vitro expansion of human T cells. Cancer immunology, immunotherapy : CII 37 19360406
2017 Important malignant and new nail tumors. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 36 28378483
2013 Identification of CD244-expressing myeloid-derived suppressor cells in patients with active tuberculosis. Immunology letters 35 24333340
2014 Bifunctional ectodermal stem cells around the nail display dual fate homeostasis and adaptive wounding response toward nail regeneration. Proceedings of the National Academy of Sciences of the United States of America 34 25277970
2012 Evaluation of nail abnormalities. American family physician 34 22534387
2011 Cutting edge: an NK cell-independent role for Slamf4 in controlling humoral autoimmunity. Journal of immunology (Baltimore, Md. : 1950) 34 21622868
2005 2B4/CD48-mediated regulation of lymphocyte activation and function. Journal of immunology (Baltimore, Md. : 1950) 34 16081768
2018 Squamous cell carcinoma of the nail unit. Dermatology practical & conceptual 33 30116671
2011 Expansion of 2B4+ natural killer (NK) cells and decrease in NKp46+ NK cells in response to influenza. Immunology 31 21214542
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