Affinage

CD58

Lymphocyte function-associated antigen 3 · UniProt P19256

Length
250 aa
Mass
28.1 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD58 (LFA-3) is a broadly distributed immunoglobulin-superfamily cell-surface adhesion and costimulatory molecule that serves as the principal high-specificity ligand for CD2 on T and NK cells, governing the formation and quality of the immunological synapse (PMID:2951597, PMID:3102675, PMID:7520278). The CD58 adhesion domain is a V-set Ig fold whose highly acidic AGFCC'C" beta-sheet face docks against the equivalent surface of CD2 in a charge-complementary "handshake"; the interaction is of very low affinity (Kd ~9-22 µM) with extremely fast dissociation kinetics, with electrostatic salt bridges driving specificity and the CD2 Tyr86-CD58 Lys34 contact acting as the dominant energetic hot spot (PMID:7520278, PMID:10200255, PMID:7525842, PMID:10357807, PMID:11575926). By engaging CD2, CD58 on antigen-presenting and target cells amplifies TCR-proximal signaling through lipid-raft aggregation and activation of AP-1, NF-AT, NF-κB and NF-IL-2 pathways, but this costimulation requires an intact CD3/TCR complex (PMID:11591762, PMID:2459194). CD58 functions on the target/APC side of cytolytic and adhesive interactions: it supports CTL killing, MHC-class-II-driven T cell costimulation and adhesion, IL-12 responsiveness, IgE class switching in B cells, and NK cell activation against virally infected targets, and it is the primary costimulatory pathway for CD28-negative CD8+ T cells (PMID:6345670, PMID:11591762, PMID:7515920, PMID:8757306, PMID:9725232, PMID:26041540, PMID:9691200). CD58 surface levels are set at multiple regulatory layers: PAX5 transcriptionally activates a CD58 enhancer, EZH2-mediated H3K27me3 silences the locus, ALKBH5-dependent m6A regulation destabilizes its mRNA, and CMTM6 stabilizes the CD58 protein by controlling its endosomal recycling versus lysosomal degradation in competition with PD-L1 (PMID:37327789, PMID:31962268, PMID:36516256, PMID:38589927). Loss of CD58 is a recurrent mechanism of tumor immune evasion: it produces suboptimal immunological synapses that impair CAR-T and endogenous T/NK effector function, stabilizes PD-L1, and activates IDO via the LYN/CD22/SHP1 axis, and CD58 status predicts response to immune checkpoint and immunotherapy (PMID:37327789, PMID:38635903, PMID:35728062, PMID:32589698).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1983 High

    Established that CD58 acts on the target-cell side of cytolytic interactions, reframing it from a generic surface antigen to a functional partner in immune effector recognition.

    Evidence Anti-LFA-3 monoclonal antibody blocking of CTL-mediated cytolysis in 51Cr-release assays, mapping function to target cells

    PMID:6345670

    Open questions at the time
    • Molecular binding partner of CD58 not yet identified
    • Mechanism of how CD58 promotes killing not defined
  2. 1987 High

    Identified CD2 as the direct binding partner of CD58, defining the receptor-ligand axis underlying T cell adhesion to lymphoid and target cells.

    Evidence Purified-protein ligand binding, rosette inhibition, and erythrocyte absorption experiments

    PMID:2951597 PMID:3102675

    Open questions at the time
    • Binding affinity and kinetics not quantified
    • Structural basis of recognition unknown
  3. 1988 High

    Showed that CD58-CD2 engagement requires the antigen-receptor machinery to deliver activation signals, linking the adhesion axis to TCR-dependent T cell activation rather than independent signaling.

    Evidence Genetic reconstitution of CD3-negative Jurkat mutants with TCR-beta and CD2 epitope-loss mutants, with calcium flux and PI hydrolysis readouts

    PMID:2448792 PMID:2459194

    Open questions at the time
    • Downstream signaling intermediates not mapped
    • Quantitative contribution of CD58 versus TCR signal not separated
  4. 1994 High

    Quantified the CD2-CD58 interaction as very-low-affinity and fast-dissociating and established CD58 as the high-specificity ligand over CD48/CD59, explaining the kinetics that permit rapid, transient adhesion.

    Evidence Surface plasmon resonance with soluble recombinant ectodomains

    PMID:7520278

    Open questions at the time
    • Structural interface not resolved
    • How fast kinetics support stable synapse adhesion unresolved
  5. 1994 High

    Defined the molecular interface as the charged AGFCC'C" beta-sheet faces of both partners, providing a structural rationale for electrostatically driven specificity.

    Evidence Reciprocal site-directed mutagenesis of CD2 and CD58 charged residues with rosetting and adhesion assays

    PMID:7525842 PMID:7688025

    Open questions at the time
    • Energetic hierarchy of individual contacts not yet established
    • No high-resolution structure of the complex interface
  6. 1999 High

    Resolved the CD58 adhesion domain structure, confirming a V-set Ig fold sharing topology with CD2 and an acidic ligand-binding face with poor shape complementarity, supporting an electrostatically driven recognition model.

    Evidence 1.8-Å X-ray crystallography and NMR solution structure with mutagenesis and titration validation

    PMID:10200255 PMID:10357807

    Open questions at the time
    • Full co-complex thermodynamics not yet measured
    • Role of glycosylation in vivo not addressed
  7. 2001 High

    Pinpointed CD2 Tyr86-CD58 Lys34 as the dominant energetic hot spot, refining the binding model from uniformly distributed electrostatics to a defined hydrophobic anchor amid salt bridges.

    Evidence Isothermal titration calorimetry with alanine-scanning mutagenesis and crystal structure analysis

    PMID:11575926

    Open questions at the time
    • Hot spot contribution to physiological adhesion strength not directly tested at the cell level here
  8. 2001 Medium

    Linked CD58-CD2 engagement to defined transcriptional programs and membrane reorganization, establishing CD58 as a costimulus that amplifies TCR signaling via lipid raft aggregation.

    Evidence Luciferase reporters for AP-1/NF-AT/NF-κB/NF-IL-2 and lipid raft aggregation assays with CD2 blocking antibodies in endothelial co-cultures

    PMID:11591762

    Open questions at the time
    • Single-lab functional pathway analysis
    • Direct molecular link between CD2 engagement and raft coalescence not defined
  9. 2006 Medium

    Connected molecular binding properties to physical adhesion mechanics, showing salt bridges set the tensile strength of the bond and that activation tunes CD2 2D affinity and mobility to strengthen contact.

    Evidence Steered molecular dynamics, surface force apparatus, SPR, and FRAP on supported bilayers with CD2 charge mutants

    PMID:12668431 PMID:17168569 PMID:17172599

    Open questions at the time
    • Computational and biophysical models from single labs
    • In vivo relevance of force-dependent rupture not tested
  10. 1994 High

    Demonstrated that CD58 signals beyond adhesion, driving IL-4-dependent IgE class switching and IL-12 responsiveness, broadening its role into B cell and T cell effector programming.

    Evidence Anti-CD58/CD2 ligation of B cells with epsilon transcript and IgE readouts; CD58-transfected CHO reconstitution of IL-12 responsiveness with CD48 negative control

    PMID:7515920 PMID:8757306

    Open questions at the time
    • Signaling intermediates downstream of CD58 ligation not mapped
    • Whether B cell CD58 signals cell-autonomously versus via CD2 partner cell unresolved
  11. 1998 High

    Established CD58 as a determinant of NK-mediated immunity against viral infection, with a quantitative surface-density threshold governing target susceptibility.

    Evidence NK cytotoxicity assays across CMV strains with flow cytometry quantification of LFA-3 density

    PMID:7682988 PMID:9725232

    Open questions at the time
    • Mechanism by which CMV upregulates CD58 not defined
    • Receptor on NK cells (CD2) contribution not formally isolated in this study
  12. 2020 High

    Identified transcriptional and epigenetic control of CD58 expression, showing PAX5 activates and EZH2-mediated H3K27me3 silences the locus, defining mechanisms that set CD58 surface abundance.

    Evidence Epigenetic inhibitor screen with ChIP for H3K27me3 and IFN-γ rescue; genome-wide and transcription-factor CRISPR screens with PAX5 P80R editing and ATAC/ChIP enhancer mapping

    PMID:31962268 PMID:36516256

    Open questions at the time
    • Interplay between PAX5 and EZH2 control not integrated
    • Tissue specificity of these regulatory mechanisms not defined
  13. 2023 High

    Revealed post-translational control of CD58 by CMTM6, coupling CD58 protein stability to PD-L1 stability through competitive endosomal recycling and providing a mechanistic link between CD58 loss and checkpoint resistance.

    Evidence CRISPR screens, proteomics, co-IP, patient-derived co-cultures, and humanized mouse models

    PMID:37327789

    Open questions at the time
    • Structural basis of CMTM6 competition between CD58 and PD-L1 not resolved
    • Whether other CMTM family members participate not addressed
  14. 2024 Medium

    Extended CD58 loss to active immune evasion signaling, showing it represses JAK2/STAT1 via the LYN/CD22/SHP1 axis to elevate PD-L1 and IDO, and that m6A regulation destabilizes CD58 mRNA in cancer.

    Evidence Co-IP for LYN/CD22/SHP1 and HSPA4/ALKBH5, meRIP, RNA-seq/WES/scRNA-seq, and CAR-T/cytotoxicity combination assays

    PMID:38589927 PMID:38635903

    Open questions at the time
    • Single-lab mechanistic chains awaiting orthogonal confirmation
    • How CD58 surface engagement transduces into intracellular JAK2/STAT1 suppression not fully defined
  15. 2022 High

    Established CD58 loss as a clinically relevant mechanism of immunotherapy resistance, with deficient cells forming suboptimal synapses that cripple CAR-T and endogenous effector function.

    Evidence Genome-wide CRISPR screens with knockout validation, in vitro/in vivo CAR-T functional assays, rosetting and proximity ligation assays in primary lymphoma tissue

    PMID:32589698 PMID:35728062

    Open questions at the time
    • Quantitative synapse defect not mechanistically linked to specific signaling deficits
    • Strategies to restore CD58 in vivo not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple layers of CD58 regulation (PAX5/EZH2 transcription, ALKBH5 m6A, CMTM6 protein stability, soluble CD58 shedding) are integrated to set functional surface density across tissues and tumor contexts remains unresolved.
  • No unified model linking transcriptional, epigenetic, m6A, and protein-stability control
  • Physiological role of soluble homotrimeric CD58 in modulating adhesion in vivo not established
  • Intracellular signaling consequences of CD58 ligation in non-canonical pathways (Wnt/DKK3, JAK2/STAT1) not mechanistically connected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0005198 structural molecule activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-1500931 Cell-Cell communication 2
Partners
CD2CMTM6DKK3

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 CD2 (LFA-2/T11) directly binds LFA-3 (CD58) on cell surfaces, mediating T cell adhesion to lymphoid cells; purified CD2 inhibits T-cell rosetting with human erythrocytes and is absorbed by sheep erythrocytes expressing LFA-3, establishing CD58 as the natural ligand for CD2. Ligand binding with purified protein, rosette inhibition assay, absorption experiments Nature High 2951597 3102675
1983 LFA-3 (CD58) is widely distributed on hematopoietic and non-hematopoietic tissues; anti-LFA-3 monoclonal antibodies block CTL-mediated cytolysis by binding to target cells (not effector cells), indicating CD58 functions on target cells in CTL interactions. Monoclonal antibody generation and 51Cr-release cytotoxicity blocking assay Journal of immunology High 6345670
1994 Human CD2 binds CD58 with very low affinity (Kd 9–22 µM) and an extremely fast dissociation rate (koff ≥ 4 s⁻¹); CD2 does not detectably bind CD48 or CD59 under the same conditions, establishing CD58 as the primary high-specificity ligand for human CD2. Surface plasmon resonance (BIAcore) with soluble recombinant ectodomains Biochemistry High 7520278
1999 Crystal structure of the CD2-binding domain of CD58 at 1.8-Å resolution reveals an Ig superfamily V-set topology shared with CD2; the ligand-binding surface of CD58 is the highly acidic AGFCC'C" beta-sheet face; mutations that disrupt CD2 binding map to this surface, and the interface lacks strong shape complementarity, suggesting electrostatic complementarity drives specificity. X-ray crystallography at 1.8 Å with functional mutagenesis validation Proceedings of the National Academy of Sciences of the United States of America High 10200255
1993 The CD58-binding site on CD2 maps to the major AGFCC'C" beta-sheet face of domain 1; substitution of residues K34, E36 (strand C), R48, K49 (strand C'), and K91, N92 (FG loop) abrogates rosetting with human and sheep erythrocytes, demonstrating that these charged residues are critical for CD2–CD58 interaction. Site-directed mutagenesis of CD2 combined with rosetting assay The Journal of experimental medicine High 7688025
1994 The CD58 binding surface on CD2 involves residues on the C, C', and CC' loop strands; mutating charged residues E25, K29, K30 (C strand), E37 (C' strand), K32, D33, K34 (CC' loop), and K87 (G strand) of CD58 reduces CD2 binding, establishing that CD2–CD58 interaction involves the major beta-sheet surface of each adhesion domain in a 'handshake' orientation. Site-directed mutagenesis of CD58 combined with cell adhesion and rosetting assays The Journal of experimental medicine High 7525842
1999 NMR solution structure of a glycan-free CD58 adhesion domain confirms binding to CD2 involves the GFCC'C" faces of both molecules; chemical shift perturbations in NMR titration localize the binding site to C, C', and C" strands and loops of CD58. NMR spectroscopy with titration experiments using recombinant CD58 adhesion domain The EMBO journal High 10357807
2001 The functional hot spot of the CD2–CD58 interface is defined by CD2 Tyr86 and CD58 Lys34; alanine scanning of salt-bridge residues shows D31A, D32A, K34A, K43A, R48A reduce affinity 47–127-fold, while Y86A reduces affinity ~1000-fold; crystal structure analysis shows CD2 Y86 makes hydrophobic contact with the aliphatic chain of CD58 K34. Isothermal titration calorimetry with alanine-scanning mutagenesis; crystal structure analysis Journal of molecular biology High 11575926
2001 CD58 engagement of CD2 on T cells activates AP-1, NF-AT, NF-κB, and NF-IL-2 transcriptional pathways and promotes lipid raft aggregation on T cells, amplifying TCR signaling; anti-CD2 antibodies block all these effects and EC-induced raft aggregation. Luciferase reporter assays for transcription factors, lipid raft aggregation assay with CD2 blocking antibodies in CD58-expressing endothelial cell co-cultures Journal of immunology Medium 11591762
1988 LFA-3 activates T cells via CD2 under appropriate conditions, but this activation requires both cell surface expression of CD3/TCR complex and a functional antigen receptor pathway; a CD3-negative CD2+ Jurkat mutant fails to respond to LFA-3 plus anti-CD2, and TCR-β chain transfection restores responsiveness. Genetic reconstitution in Jurkat mutants; calcium flux and phosphatidylinositol hydrolysis assays Journal of immunology High 2459194
1991 GPI-anchored LFA-3 (CD58) diffuses laterally in membranes with a coefficient approaching phospholipids, whereas transmembrane LFA-3 is immobile; GPI-anchored LFA-3 supports faster and more efficient adhesion strengthening with CD2+ T cells at low site densities due to receptor accumulation in the contact zone. Reconstituted planar lipid bilayers with two LFA-3 isoforms; static and laminar flow adhesion assays; fluorescence recovery measurements The Journal of cell biology High 1717480
1998 Both the GPI-anchored and transmembrane forms of CD58 associate with protein kinase(s); crosslinking either isoform with immobilized anti-CD58 antibodies induces extensive tyrosine phosphorylation and TNF-alpha secretion in B cells, establishing CD58's role in signal transduction independent of anchor type. Immunoprecipitation kinase assay; comparison of JY variant cells expressing only one isoform; anti-CD58 crosslinking with tyrosine phosphorylation readout Journal of immunology Medium 9574540
1994 Ligation of B cell CD58 by CD2 or by anti-CD58 monoclonal antibody provides an IL-4-dependent signal that drives IgE class switch recombination (inducing productive ε transcripts and IgE protein production) distinct from the CD40 pathway; direct CD2 involvement was confirmed by co-culture with CD2-transfected T hybridoma cells. Purified B cells co-stimulated with IL-4 and anti-CD58 mAb; RT-PCR for ε transcripts; ELISA for IgE; CD40-Fc fusion protein competition; CD2-transfected hybridoma co-culture Journal of immunology High 7515920
1996 CD2–CD58 interaction between T cells and monocytes specifically regulates T cell responsiveness to IL-12; CHO cells expressing CD58 at monocyte-equivalent levels restore IL-12 responsiveness to APC-depleted T cells, whereas CD48-expressing CHO cells (low avidity CD2 ligand) do not, demonstrating that high-avidity CD58–CD2 ligation is required for IL-12 co-signaling. APC-depletion experiments; CD58-transfected CHO cell reconstitution; proliferation assays; anti-CD2/CD58 blocking antibodies Journal of immunology High 8757306
1993 TCR stimulation rapidly upregulates CD2 avidity for CD58; this regulation requires both protein tyrosine kinase activity and protein kinase C activity, and requires the carboxyl-terminal asparagine of the CD2 cytoplasmic domain; cAMP elevation also upregulates CD2 avidity through the same structural element. CD2 avidity assay (cell binding to purified CD58 and SRBC rosetting); kinase inhibitors; CD2 cytoplasmic domain single amino acid substitution mutants in Jurkat hybridomas Journal of immunology High 7681075
2006 T cell activation increases CD2 surface expression 1.5-fold and the 2D affinity of CD2 for CD58 2.5-fold; combined T cell activation and CD2 ligation to CD58 decreases the laterally mobile fraction of CD2, consistent with cytoskeletal immobilization at the contact site to strengthen T cell–APC adhesion. Fluorescence recovery after photobleaching (FRAP); quantitative surface receptor measurements; 2D affinity measurements on supported lipid bilayers ACS chemical biology Medium 17168569
2003 Steered molecular dynamics simulations show that at slow loading rates CD2 and CD58 separate before unfolding; salt bridges primarily determine tensile strength of the CD2–CD58 bond, and the order of salt bridge rupture correlates with their position relative to the force vector; simulation results correlate with cell aggregation and equilibrium binding data from site-directed mutagenesis. Steered molecular dynamics simulations; correlation with published mutagenesis data Biophysical journal Medium 12668431
2006 Quantitative surface force apparatus measurements confirm that single charge mutations at CD2 D31, K41, K51, K91 alter both solution-phase binding kinetics (SPR) and cell adhesion strength for the CD2–CD58 interaction, validating the role of specific salt bridges in adhesion. Surface plasmon resonance; surface force apparatus adhesion measurements with CD2 charge mutants The Journal of biological chemistry Medium 17172599
1989 Anti-LFA-3 monoclonal antibody crosslinks LFA-3 and induces lateral immobilization of class I and class II MHC proteins in the plasma membrane of B cells, suggesting that CD2 binding to LFA-3 on target cells may immobilize and concentrate MHC molecules at the T cell–target cell interface. Fluorescence photobleaching recovery (FPR) on JY B cells; bivalent vs. monovalent fluorescent antibody comparison European journal of immunology Medium 2471647
1998 NK cell lysis of CMV-infected fibroblasts correlates with upregulation of LFA-3 (CD58) on infected cells, not with MHC class I downregulation; viral strains that upregulate LFA-3 render cells susceptible to NK killing, while strains that downregulate LFA-3 make cells resistant; a minimum of 29,000–71,000 LFA-3 molecules per target are required for NK susceptibility. NK cytotoxicity assay with multiple CMV strains; flow cytometry for LFA-3 and MHC I; quantitative threshold analysis Journal of immunology High 9725232
2003 Coexpression of CD58 (or CD48) with ICAM-1 on target cells enhances adhesion of resting NK cells beyond that mediated by ICAM-1 alone, in the absence of cytokine priming; receptors for LFA-3 on resting NK cells strengthen LFA-1–mediated adhesion. Drosophila cells expressing defined combinations of human ligands; NK cell adhesion assays with kinase inhibitors Journal of immunology Medium 12496412
2023 CMTM6 is required for CD58 protein stability; loss of CD58 leads to increased PD-L1 protein stabilization because CD58 and PD-L1 compete for CMTM6 binding, which determines their rate of endosomal recycling versus lysosomal degradation; intact cancer cell CD58 expression and ligation of CD2 is required for anti-tumor immunity and predicts checkpoint blockade response. CRISPR-Cas9 screens; proteomics; patient-derived co-cultures; humanized mouse models; single-cell RNA-seq of patient biopsies; co-immunoprecipitation for CMTM6 interactions Cancer cell High 37327789
2020 EZH2 epigenetically silences CD58 expression in B-cell lymphoma cells through H3K27 trimethylation at the CD58 promoter; EZH2 inhibitors (EPZ6438, GSK126) restore CD58 expression by demethylating H3K27me3 at the CD58 locus and enhance T/NK cell IFN-γ production against lymphoma cells. Epigenetic inhibitor library screen; ChIP for H3K27me3 at CD58 promoter; flow cytometry; IFN-γ functional assay Molecular immunology Medium 31962268
2022 PAX5 is the key transcriptional activator of CD58 in B-ALL; PAX5 P80R mutation disrupts a PAX5-driven enhancer at the CD58 locus, reducing CD58 expression; loss of CD58 confers resistance to blinatumomab by abolishing blinatumomab-induced T cell activation; identified by genome-wide CRISPR screen followed by transcription factor screen of 1639 genes. Genome-wide CRISPR screen; transcription factor CRISPR screen; genome editing to introduce/correct PAX5 P80R; ChIP/ATAC-seq for enhancer; co-culture cytotoxicity assay Science advances High 36516256
2024 CD58 inhibits JAK2/STAT1 pathway activity by activating the LYN/CD22/SHP1 axis; loss of CD58 in DLBCL leads to elevated PDL1 and IDO expression through this pathway, contributing to immune evasion; direct CD58–CD2 costimulation combined with anti-PDL1 or IDO inhibitor sensitizes CD58-deficient DLBCL to CAR-T therapy. Targeted NGS, RNA-seq, WES, scRNA-seq; co-IP for pathway components; pharmacological inhibitor combinations; CAR-T cytotoxicity assays Cancer research Medium 38635903
2024 HSPA4 upregulation increases ALKBH5 protein stability; ALKBH5 (m6A demethylase) decreases CD58 mRNA in gastric cancer cells through m6A methylation regulation, reducing CD8+ T cell cytotoxicity and activating PD1/PDL1 axis. Co-immunoprecipitation; meRIP (m6A RNA immunoprecipitation); co-culture cytotoxicity assay; HSPA4 overexpression/knockdown Journal of experimental & clinical cancer research Medium 38589927
1988 CD2 expression on a murine T cell hybridoma greatly enhances T cell responsiveness to antigen in an LFA-3-dependent manner; a CD2 mutant lacking the mAb 9.6 epitope loses both enhanced antigen responsiveness and LFA-3-driven activation but retains activation by anti-CD2 antibody pairs, indicating the CD2–LFA-3 interaction requires an intact CD2 extracellular epitope. cDNA expression of wild-type and mutant CD2 in murine T cell hybridoma; IL-2 production assays; anti-CD2 and anti-LFA-3 blocking antibodies Proceedings of the National Academy of Sciences of the United States of America High 2448792
2022 Genome-wide CRISPR/Cas9 screen identifies CD58 loss as a mechanism of tumor resistance to CAR T cell therapy; CD58-deficient tumor cells form suboptimal immunological synapses with CAR T cells, impairing CAR T cell expansion, degranulation, cytokine secretion, and cytotoxicity in vitro and in vivo. Genome-wide CRISPR/Cas9 screen; CD58 knockout validation; in vitro CAR T functional assays; in vivo xenograft model; immunological synapse analysis Blood advances High 35728062
2015 CD58/CD2 axis is the primary costimulatory pathway in CD28-negative CD8+ T cells; CD58 on APCs (including dendritic cells) engages CD2 on CD28⁻CD8⁺ T cells to costimulate proliferation, cytokine production, and effector function; CD2 engagement amplifies TCR signals in this subset. Blocking anti-CD58 mAb in allogeneic DC assays; viral antigen recall responses; T cell proliferation and cytokine assays Journal of immunology Medium 26041540
2009 The protective rs2300747(G) allele of CD58 is associated with dose-dependent increases in CD58 mRNA expression in lymphoblastic cell lines and PBMCs; increased CD58 expression upregulates FoxP3 expression through engagement of CD2, enhancing function of CD4+CD25high regulatory T cells. Fine mapping and resequencing; dose-dependent mRNA expression analysis; functional CD58–CD2 engagement assay measuring FoxP3 induction Proceedings of the National Academy of Sciences of the United States of America Medium 19237575
1999 CD58 is expressed constitutively on the basolateral surface of polarized intestinal epithelial cells (but not CD80 or CD86); this basolateral CD58 acts as the costimulatory molecule mediating HLA class II antigen presentation to CD4+ T cells, as anti-CD58 antibodies block IEC-stimulated T cell proliferation while anti-CD80/CD86 do not. Flow cytometry; confocal microscopy; vectorial biotinylation to determine polarized localization; antibody blocking of T cell proliferation Gastroenterology Medium 10220497
1993 CMV infection directly upregulates LFA-3 and ICAM-1 cell-surface expression on fibroblasts; this is a direct viral effect (not cytokine-mediated) requiring infectious virus; LFA-3 accumulates in perinuclear granules in infected cells vs. diffuse cytoplasmic distribution in uninfected cells. Flow cytometry; neutralizing antibody experiments against candidate cytokines; UV-inactivated virus controls; confocal scanning laser microscopy; immunofluorescence Immunology Medium 7682988
2016 CD2–CD58 binding is required for activation and effector functions of adaptive (NKG2C+CD57+) NK cells in response to HCMV-infected cells; antibody blockade of CD2 or CD58 largely blocks upregulation of activation markers (CD69, CD25, HLA-DR) and production of IFN-γ and TNF-α specifically in adaptive NK cells. Co-culture of human PBMCs with HCMV-infected fibroblasts; CD2/CD58 blocking antibodies; flow cytometry for activation markers and intracellular cytokines European journal of immunology Medium 27469079
2020 CD58 expression on Hodgkin lymphoma Reed-Sternberg cells determines extent of T cell rosette formation and T cell activation; CD58 knockout or CD2 blockade reduces both rosetting and T cell activation; proximity ligation assays in primary HL tissue confirm CD2–CD58 interactions at the immunological synapse. CD58 knockout by CRISPR (CIITA KO for HLA-II comparison); rosetting co-culture model; proximity ligation assay on primary tissue; flow cytometry for T cell activation Blood High 32589698
2014 CD58 promotes self-renewal of colorectal tumor-initiating cells by upregulating the Wnt/β-catenin pathway through degradation of Dickkopf 3 (DKK3); CD58 knockdown impairs sphere formation and tumor growth; CD58–DKK3 interaction identified by co-immunoprecipitation and western blotting. cDNA GeneChip; flow cytometry; sphere formation assay; xenograft in vivo; co-immunoprecipitation and western blot for DKK3 degradation; lentiviral CD58 knockdown Oncogene Medium 24727892
1998 MHC class II ligation induces homotypic T cell adhesion that is almost completely inhibited by anti-CD58 antibody and partly by anti-CD2 antibody, establishing that CD58–CD2 interaction is required for class-II-induced T cell aggregation; demonstrated in β2-integrin-deficient T cells confirming β2-integrin independence. Cell aggregation assay with blocking monoclonal antibodies in β2-integrin-negative (LAD patient) T cell lines Experimental and clinical immunogenetics Medium 9691200
1993 Soluble CD58 (sCD58) is present as a natural protein in human serum, urine, and cell culture supernatants; it forms noncovalent homotrimers (~118–166 kDa by gel filtration) and at high concentrations binds to CD2+ T cells and inhibits rosette formation, suggesting sCD58 can suppress CD2–CD58-mediated adhesion in vivo. ELISA; SDS-PAGE and Western blotting; gel filtration; T cell rosette inhibition assay European journal of immunology Medium 7693485

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1988 Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. Journal of immunology (Baltimore, Md. : 1950) 1021 2894392
1983 The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions. Journal of immunology (Baltimore, Md. : 1950) 695 6345670
1987 The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3. Nature 520 2951597
2011 Combined genetic inactivation of β2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer cell 374 22137796
1988 Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. The Journal of experimental medicine 324 2898508
1993 Expression patterns of leukocyte adhesion ligand molecules on human liver endothelia. Lack of ELAM-1 and CD62 inducibility on sinusoidal endothelia and distinct distribution of VCAM-1, ICAM-1, ICAM-2, and LFA-3. The American journal of pathology 194 8434643
1994 Human cell-adhesion molecule CD2 binds CD58 (LFA-3) with a very low affinity and an extremely fast dissociation rate but does not bind CD48 or CD59. Biochemistry 192 7520278
1992 Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science (New York, N.Y.) 179 1377404
1991 Influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2. The Journal of cell biology 174 1717480
2009 The role of the CD58 locus in multiple sclerosis. Proceedings of the National Academy of Sciences of the United States of America 149 19237575
1987 Rosetting of activated human T lymphocytes with autologous erythrocytes. Definition of the receptor and ligand molecules as CD2 and lymphocyte function-associated antigen 3 (LFA-3). The Journal of experimental medicine 148 3102675
1988 The CD2 ligand LFA-3 activates T cells but depends on the expression and function of the antigen receptor. Journal of immunology (Baltimore, Md. : 1950) 147 2459194
1995 T cell activation pathways: B7, LFA-3, and ICAM-1 shape unique T cell profiles. Critical reviews in immunology 129 8834450
1993 Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells. Cancer research 122 7686816
1988 Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation. Proceedings of the National Academy of Sciences of the United States of America 112 2448792
1992 Expression and regulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human intestinal epithelial cell lines. Scandinavian journal of immunology 110 1376489
2008 Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes and immunity 106 18650830
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
1993 Up-regulation of LFA-3 and ICAM-1 on the surface of fibroblasts infected with cytomegalovirus. Immunology 89 7682988
2015 CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28-CD8+ T Cells. Journal of immunology (Baltimore, Md. : 1950) 85 26041540
1992 CD58 and CD59 molecules exhibit potentializing effects in T cell adhesion and activation. Journal of immunology (Baltimore, Md. : 1950) 83 1370512
1992 Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells. British journal of haematology 75 1382543
2003 Coexpression of CD58 or CD48 with intercellular adhesion molecule 1 on target cells enhances adhesion of resting NK cells. Journal of immunology (Baltimore, Md. : 1950) 72 12496412
2023 The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity. Cancer cell 71 37327789
1996 Molecular interaction between CD58 and CD2 counter-receptors mediates the ability of monocytes to augment T cell activation by IL-12. Journal of immunology (Baltimore, Md. : 1950) 71 8757306
1996 Cytomegalovirus induced up-regulation of LFA-3 (CD58) and ICAM-1 (CD54) is a direct viral effect that is not prevented by ganciclovir or foscarnet treatment. Transplantation 70 8900310
1998 Natural killer cell lysis of cytomegalovirus (CMV)-infected cells correlates with virally induced changes in cell surface lymphocyte function-associated antigen-3 (LFA-3) expression and not with the CMV-induced down-regulation of cell surface class I HLA. Journal of immunology (Baltimore, Md. : 1950) 69 9725232
1989 IL-4 induces LFA-1 and LFA-3 expression on Burkitt's lymphoma cell lines. Requirement of additional activation by phorbol myristate acetate for induction of homotypic cell adhesions. Journal of immunology (Baltimore, Md. : 1950) 68 2547869
2021 CD58 Immunobiology at a Glance. Frontiers in immunology 65 34168659
1991 New monoclonal antibodies in CD44 and CD58: their use to quantify CD44 and CD58 on normal human erythrocytes and to compare the distribution of CD44 and CD58 in human tissues. Immunology 65 1721039
2003 Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia. Haematologica 63 14607753
1995 Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines. International journal of cancer 62 7530239
2016 CD2-CD58 interactions are pivotal for the activation and function of adaptive natural killer cells in human cytomegalovirus infection. European journal of immunology 60 27469079
2022 CD58 loss in tumor cells confers functional impairment of CAR T cells. Blood advances 56 35728062
1990 Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus. Blood 55 1691936
1993 Immune modulation of adhesion molecules ICAM-1 (CD54) and LFA-3 (CD58) in human hepatocytic cell lines. Journal of hepatology 54 7686194
1999 Crystal structure of the CD2-binding domain of CD58 (lymphocyte function-associated antigen 3) at 1.8-A resolution. Proceedings of the National Academy of Sciences of the United States of America 52 10200255
2022 Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses. The Journal of clinical investigation 50 35881486
1994 CD58 (LFA-3) stimulation provides a signal for human isotype switching and IgE production distinct from CD40. Journal of immunology (Baltimore, Md. : 1950) 50 7515920
2001 CD58/LFA-3 and IL-12 provided by activated monocytes are critical in the in vitro expansion of CD56+ T cells. Cancer immunology, immunotherapy : CII 48 11258789
1993 Mutational analysis of the CD2/CD58 interaction: the binding site for CD58 lies on one face of the first domain of human CD2. The Journal of experimental medicine 47 7688025
2003 Forced detachment of the CD2-CD58 complex. Biophysical journal 45 12668431
2020 Rosetting T cells in Hodgkin lymphoma are activated by immunological synapse components HLA class II and CD58. Blood 44 32589698
1991 Adhesion molecules in human islet beta-cells. De novo induction of ICAM-1 but not LFA-3. Diabetes 44 1718801
1994 Interaction between human CD2 and CD58 involves the major beta sheet surface of each of their respective adhesion domains. The Journal of experimental medicine 43 7525842
1993 Signal transduction pathways involved in T cell receptor-induced regulation of CD2 avidity for CD58. Journal of immunology (Baltimore, Md. : 1950) 43 7681075
1990 Selective and non-selective loss of immunoregulatory molecules (HLA-A,B,C antigens and LFA-3) in transitional cell carcinoma. British journal of cancer 43 1699592
2014 CD58, a novel surface marker, promotes self-renewal of tumor-initiating cells in colorectal cancer. Oncogene 41 24727892
1995 Human luteal cells express leukocyte functional antigen (LFA)-3. The Journal of clinical endocrinology and metabolism 41 7530258
1993 Differential expression and release of LFA-3 and ICAM-1 in human melanoma cell lines. International journal of cancer 41 7685328
1991 Dual function of recombinant human CD58: inhibition of T cell adhesion and activation via the CD2 pathway. International immunology 41 1723296
2016 CD58 mutations are common in Hodgkin lymphoma cell lines and loss of CD58 expression in tumor cells occurs in Hodgkin lymphoma patients who relapse. Genes and immunity 40 27467287
2006 Mechanisms of Cellular Avidity Regulation in CD2-CD58-Mediated T Cell Adhesion. ACS chemical biology 39 17168569
2001 Molecular dissection of the CD2-CD58 counter-receptor interface identifies CD2 Tyr86 and CD58 Lys34 residues as the functional "hot spot". Journal of molecular biology 39 11575926
2001 Endothelial cell costimulation of T cell activation through CD58-CD2 interactions involves lipid raft aggregation. Journal of immunology (Baltimore, Md. : 1950) 39 11591762
1996 Histamine selectively enhances human immunoglobulin E (IgE) and IgG4 production induced by anti-CD58 monoclonal antibody. The Journal of experimental medicine 39 8760789
1992 Structural and functional epitopes of the human adhesion receptor CD58 (LFA-3). European journal of immunology 39 1385151
1992 Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in Epstein-Barr-virus-positive nasopharyngeal carcinoma cells. International journal of cancer 37 1372880
1991 Frequency of abnormal expression of HLA-A,B,C and HLA-DR molecules, invariant chain, and LFA-3 (CD58) in colorectal carcinoma and its impact on tumor recurrence. International journal of cancer. Supplement = Journal international du cancer. Supplement 37 1712347
1999 Functional glycan-free adhesion domain of human cell surface receptor CD58: design, production and NMR studies. The EMBO journal 36 10357807
1993 A soluble form of the adhesion receptor CD58 (LFA-3) is present in human body fluids. European journal of immunology 36 7693485
1988 Role of the LFA3-CD2 interaction in human specific B cell differentiation. Journal of immunology (Baltimore, Md. : 1950) 36 2459195
2015 Alterations of the CD58 gene in classical Hodgkin lymphoma. Genes, chromosomes & cancer 35 26194173
1986 Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions. Journal of immunology (Baltimore, Md. : 1950) 35 3514752
2020 EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas. Molecular immunology 33 31962268
2016 Constrained Cyclic Peptides as Immunomodulatory Inhibitors of the CD2:CD58 Protein-Protein Interaction. ACS chemical biology 33 27337048
1994 CD59 costimulation of T cell activation. CD58 dependence and requirement for glycosylation. Journal of immunology (Baltimore, Md. : 1950) 33 7521361
1999 Polarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells. Gastroenterology 32 10220497
1992 The expression and role in T cell adhesion of LFA-3 and ICAM-2 on human thyroid cells. Clinical immunology and immunopathology 32 1376653
2022 Cancer cell-intrinsic resistance to BiTE therapy is mediated by loss of CD58 costimulation and modulation of the extrinsic apoptotic pathway. Journal for immunotherapy of cancer 30 35296559
2019 Decreased erythrocyte CD44 and CD58 expression link e-waste Pb toxicity to changes in erythrocyte immunity in preschool children. The Science of the total environment 30 30763849
2018 Costimulatory Function of Cd58/Cd2 Interaction in Adaptive Humoral Immunity in a Zebrafish Model. Frontiers in immunology 30 29904386
2011 Conformationally constrained peptides from CD2 to modulate protein-protein interactions between CD2 and CD58. Journal of medicinal chemistry 29 21755948
2022 PAX5 epigenetically orchestrates CD58 transcription and modulates blinatumomab response in acute lymphoblastic leukemia. Science advances 27 36516256
1994 Polyclonal B cell activation induced by herpesvirus saimiri-transformed human CD4+ T cell clones. Role for membrane TNF-alpha/TNF-alpha receptors and CD2/CD58 interactions. Journal of immunology (Baltimore, Md. : 1950) 27 7525717
2014 CD58 polymorphisms associated with the risk of neuromyelitis optica in a Korean population. BMC neurology 26 24655566
2005 CD58 expression decreases as nonmalignant B cells mature in bone marrow and is frequently overexpressed in adult and pediatric precursor B-cell acute lymphoblastic leukemia. American journal of clinical pathology 26 15762287
2004 Immunotherapeutic effects of T11TS/S-LFA3 against nitrosocompound mediated neural genotoxicity. Toxicology letters 25 15110076
1998 MHC class II ligation induces CD58 (LFA-3)-mediated adhesion in human T cells. Experimental and clinical immunogenetics 25 9691200
1994 Expression of adhesion molecules CD11/CD18 (Leu-CAMs, beta 2-integrins), CD54 (ICAM-1) and CD58 (LFA-3) in B-chronic lymphocytic leukemia. Leukemia & lymphoma 25 7519509
2003 Red blood cells promote survival and cell cycle progression of human peripheral blood T cells independently of CD58/LFA-3 and heme compounds. Cellular immunology 24 14572797
1999 Differential expression of adhesion molecules (CD44, ICAM-1 and LFA-3) in cancer cells grown in monolayer or as multicellular spheroids. Anticancer research 24 10470114
1991 Cell surface expression of ICAM-1 (CD54) and LFA-3 (CD58), two adhesion molecules, is up-regulated on bone marrow leukemic blasts after in vivo administration of high-dose recombinant interleukin-2. Journal of immunotherapy : official journal of the Society for Biological Therapy 24 1722705
2024 HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer. Journal of experimental & clinical cancer research : CR 23 38589927
2024 CD58 Alterations Govern Antitumor Immune Responses by Inducing PDL1 and IDO in Diffuse Large B-Cell Lymphoma. Cancer research 23 38635903
2001 Effects of co-stimulation by CD58 on human T cell cytokine production: a selective cytokine pattern with induction of high IL-10 production. International immunology 23 11157851
1996 Expression of glycosyl-phosphatidylinositol-linked glycoproteins in blood cells from paroxysmal nocturnal haemoglobinuria patients: a flow cytometry study using CD55, CD58 and CD59 monoclonal antibodies. Leukemia & lymphoma 23 8907282
2017 T Cell Activation Pathways: B7, LFA-3, and ICAM-1 Shape Unique T Cell Profiles. Critical reviews in immunology 22 29773030
1995 Expression of leukocyte cell adhesion molecules on gastric carcinomas: possible involvement of LFA-3 expression in the development of distant metastases. International journal of cancer 22 8550244
1994 The effects of an immunomodulatory LFA3-IgG1 fusion protein on nonhuman primates. Therapeutic immunology 22 7584496
1989 A monoclonal antibody to LFA-3, the CD2 ligand, specifically immobilizes major histocompatibility complex proteins. European journal of immunology 22 2471647
2006 Impact of salt bridges on the equilibrium binding and adhesion of human CD2 and CD58. The Journal of biological chemistry 21 17172599
2003 A recombinant vector expressing transgenes for four T-cell costimulatory molecules (OX40L, B7-1, ICAM-1, LFA-3) induces sustained CD4+ and CD8+ T-cell activation, protection from apoptosis, and enhanced cytokine production. Cellular immunology 20 12798307
1996 CD2-CD58 interaction and the control of T-cell interleukin-12 responsiveness. Adhesion molecules link innate and acquired immunity. Annals of the New York Academy of Sciences 20 8958918
2014 Immunoregulatory T cells, LFA-3 and HLA-DR in autoimmune thyroid diseases. Indian journal of endocrinology and metabolism 19 25143920
2013 Immunosuppression by co-stimulatory molecules: inhibition of CD2-CD48/CD58 interaction by peptides from CD2 to suppress progression of collagen-induced arthritis in mice. Chemical biology & drug design 19 23530775
1993 Enhanced expression of LFA-3 on human T-cell lines and leukemic cells carrying human T-cell-leukemia virus type 1. International journal of cancer 19 7503960
2004 A novel, rapid and sensitive heterotypic cell adhesion assay for CD2-CD58 interaction, and its application for testing inhibitory peptides. Journal of immunological methods 18 15345303
2002 Preclinical Changes in Immunoreactivity and Cellular Architecture during the Progressive Development of Intracranial Neoplasms and an Immunotherapeutic Schedule with a Novel Biological Response Modifier, the T11TS / S-LFA3. Asian Pacific journal of cancer prevention : APJCP 18 12716291
1998 The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 associate with protein kinases. Journal of immunology (Baltimore, Md. : 1950) 18 9574540

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