Affinage

CD80

T-lymphocyte activation antigen CD80 · UniProt P33681

Round 2 corrected
Length
288 aa
Mass
33.0 kDa
Annotated
2026-04-28
130 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD80 (B7-1) is a homodimeric type I transmembrane glycoprotein of the immunoglobulin superfamily expressed on activated antigen-presenting cells that functions as a central costimulatory and coinhibitory ligand governing T cell activation, tolerance, and immune checkpoint signaling. CD80 binds CD28 (Kd ~4 μM) to deliver T cell costimulatory signals promoting proliferation and IL-2 production, and binds CTLA-4 (Kd ~0.42 μM) with ~10-fold higher affinity and very fast kinetics to form zipper-like oligomeric lattices that favor stable inhibitory signaling; CTLA-4 additionally depletes CD80 from APCs by trans-endocytosis, reducing costimulatory capacity (PMID:9053440, PMID:11279502, PMID:21474713). On the same cell surface, CD80 interacts with PD-L1 exclusively in cis, sequestering PD-L1 from engaging PD-1 on T cells and thereby restricting PD-1-mediated coinhibition while preserving CD28-dependent costimulation (PMID:29871885, PMID:31000591). Beyond its canonical immune role, CD80 is induced on podocytes upon injury and signals through an Hsp90ab1–LRP5–β-catenin pathway to reorganize the actin cytoskeleton and promote glomerulosclerosis, while in B cells, B7-1/B7-2 engagement directly enhances IgG secretion through XBP-1-dependent mechanisms (PMID:15146236, PMID:35710882, PMID:19933871).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    The molecular identity of the T cell costimulatory ligand on activated B cells was unknown; cloning of CD80 (B7) established it as a type I transmembrane IgSF glycoprotein with V-like and C-like extracellular domains, providing the molecular basis for costimulation research.

    Evidence cDNA cloning from activated B cells with expression in COS cells, immunoprecipitation, and Northern blot

    PMID:2794510

    Open questions at the time
    • Counterreceptor on T cells not yet identified
    • Signaling mechanism downstream of CD80 engagement unknown
  2. 1991 High

    The identity of the T cell receptor for CD80 was resolved when CD28 was shown to be the direct binding partner mediating costimulatory proliferation and IL-2 production, with cross-species conservation confirmed by murine CD80 cloning.

    Evidence Fusion protein binding assay (Kd ~200 nM), CD28-transfected CHO costimulation assay, and murine B7 cloning with cross-species functional validation

    PMID:1714935 PMID:1847722

    Open questions at the time
    • CTLA-4 as second receptor not yet recognized
    • Distinction between CD80 and CD86 not yet established
  3. 1995 High

    The discovery that both CD80 and CD86 serve as shared ligands for CD28 and CTLA-4, yet differentially bias Th1/Th2 responses and EAE outcomes, established that the two B7 family members are functionally non-redundant despite binding the same counterreceptors.

    Evidence Anti-B7 blocking antibodies in EAE models, T cell differentiation assays, cytokine profiling, and stable transfectant costimulation assays

    PMID:7519245 PMID:7527824 PMID:7534215

    Open questions at the time
    • Molecular basis for differential Th1/Th2 skewing by CD80 vs CD86 unresolved
    • Relative binding affinities for CD28 vs CTLA-4 not yet quantified
  4. 1996 High

    CD80 was shown to trigger NK cell cytotoxicity through a receptor distinct from both CD28 and CTLA-4, revealing a non-canonical immune function, while CD40 signaling through specific cytoplasmic threonine residues was identified as a transcriptional inducer of CD80 expression.

    Evidence NK cytotoxicity assays with CD28-KO NK cells and blocking antibodies; CD40 mutant transfection with flow cytometry for CD80 induction

    PMID:8816387 PMID:8885864

    Open questions at the time
    • Identity of the NK cell receptor for CD80 remains unknown
    • Full CD40-to-CD80 transcriptional pathway not mapped
  5. 1997 High

    Quantitative biophysical measurement resolved the binding hierarchy: CD80 binds CTLA-4 with ~10-fold higher affinity than CD28, with extremely fast kinetics at physiological temperature, establishing the thermodynamic basis for preferential CTLA-4 engagement.

    Evidence Surface plasmon resonance (BIAcore) at 37°C with soluble recombinant proteins

    PMID:9053440

    Open questions at the time
    • How fast kinetics translate to signaling dynamics at the immunological synapse not determined
  6. 2000 High

    The crystal structure of CD80 revealed a novel IgV/IgC domain combination that forms rotationally symmetric homodimers, explaining how bivalent CD80 dimers can engage bivalent CTLA-4 dimers to build ordered signaling lattices; subsequent structures of CTLA-4/CD80 and CTLA-4/CD86 complexes defined the zipper-like oligomeric network architecture.

    Evidence X-ray crystallography (3.0 Å) of CD80 alone and in complex with CTLA-4, analytical ultracentrifugation confirming solution dimerization

    PMID:10661405 PMID:11279501 PMID:11279502

    Open questions at the time
    • Structure of CD80/CD28 complex not solved
    • How lattice organization relates to signaling output in live cells unresolved
  7. 2002 High

    Comprehensive biophysical comparison established that CD80 homodimerization (absent in monomeric CD86) and preferential CTLA-4 binding bias CD80 toward inhibitory signaling, while CD86 is relatively less biased toward CTLA-4 over CD28, explaining their distinct functional outputs despite shared receptors.

    Evidence Surface plasmon resonance and analytical ultracentrifugation comparing CD80/CD86 oligomerization and receptor affinities

    PMID:12196291

    Open questions at the time
    • Whether CD80 dimerization is regulated in vivo is unknown
    • Monovalent CD28 binding geometry implications not fully explored
  8. 2003 High

    BCL6 was identified as a direct transcriptional repressor of CD80, binding its promoter to suppress NF-κB-mediated induction downstream of CD40, establishing the transcriptional logic of CD80 regulation in germinal center B cells.

    Evidence ChIP demonstrating BCL6 binding to CD80 promoter, reporter assays, BCL6-KO mouse B cell analysis

    PMID:12860928

    Open questions at the time
    • Other transcription factors cooperating with or antagonizing BCL6 at the CD80 locus not characterized
  9. 2004 High

    Two unexpected non-canonical functions were discovered: CD80 on podocytes regulates actin cytoskeleton and glomerular permselectivity (with B7-1 KO mice protected from nephrotic syndrome), and reverse signaling through B7-1/B7-2 on dendritic cells triggers IDO enzymatic activation, establishing CD80 as a bidirectional signaling molecule.

    Evidence B7-1 KO mouse LPS-induced nephrotic syndrome model with podocyte cytoskeleton analysis; IDO activity assays with B7-1/B7-2 crosslinking and T cell subset depletion

    PMID:15034022 PMID:15146236

    Open questions at the time
    • Signaling intermediates between CD80 and actin reorganization in podocytes not yet mapped
    • Whether IDO activation by B7 requires CTLA-4 or CD28 or both remains debated
  10. 2009 High

    B cell-intrinsic B7-1/B7-2 signaling was shown to enhance IgG secretion through XBP-1 splicing induction, demonstrating that CD80/CD86 are not merely passive ligands but deliver direct signals in B cells affecting antibody production.

    Evidence Mixed bone marrow chimeras with B7-deficient B cells, in vitro B7-2 crosslinking, XBP-1 splicing RT-PCR, and antibody ELISA

    PMID:19933871

    Open questions at the time
    • Whether B7-1 and B7-2 activate identical or distinct B cell-intrinsic signaling cascades not resolved
    • Downstream pathway linking B7 engagement to XBP-1 splicing not identified
  11. 2011 High

    The mechanism by which CTLA-4 depletes costimulatory ligands was resolved: CTLA-4 physically captures CD80 and CD86 from APCs by trans-endocytosis and routes them for intracellular degradation, establishing ligand depletion as a cell-extrinsic suppressive mechanism complementing intrinsic signaling.

    Evidence Co-culture assays tracking fluorescently labeled ligand transfer, intracellular degradation assays, in vivo confirmation

    PMID:21474713

    Open questions at the time
    • Relative contribution of trans-endocytosis versus signaling-based suppression in vivo not quantified
    • Whether CD80 and CD86 are endocytosed with equal efficiency under physiological conditions unclear
  12. 2018 High

    The discovery that PD-L1 binds CD80 exclusively in cis on the same cell surface—competing with both PD-1 and CD28 binding—revealed a previously unknown checkpoint crosstalk mechanism whereby CD80 on APCs restricts PD-1-mediated coinhibition.

    Evidence NanoBiT proximity assay, cell-to-cell binding assays, competitive ELISA with purified proteins

    PMID:29871885

    Open questions at the time
    • Stoichiometry and dynamics of cis complex formation on myeloid cells in tumors not resolved
  13. 2019 High

    Genetic validation using knock-in mice in which the cis PD-L1/CD80 interaction was abolished confirmed that this interaction is essential for limiting PD-1 coinhibition during tumor immunity and autoimmunity, establishing it as a physiologically critical regulatory axis.

    Evidence Knock-in mouse model deficient in cis interaction, tumor immunity assays, autoimmune response measurements

    PMID:31000591

    Open questions at the time
    • Whether therapeutic anti-PD-L1 antibodies disrupt the cis interaction differently than anti-PD-1 antibodies needs characterization
    • Role of cis interaction in human cancers not directly validated genetically
  14. 2020 High

    Structural mapping revealed that PD-L1 binds CD80 at its dimer interface surface, distal from the CTLA-4/CD28 binding face, clarifying that CTLA-4 and CD28 do not directly compete with PD-L1 but can disrupt the cis complex by reorganizing CD80 on the cell surface.

    Evidence High-throughput FACS-based mutagenesis screen, site-directed mutagenesis of PD-L1 and B7-1, two independent cis interaction assays

    PMID:32497097

    Open questions at the time
    • Atomic-resolution structure of the PD-L1/CD80 cis complex not yet solved
  15. 2022 Medium

    The podocyte injury signaling pathway downstream of CD80 was molecularly defined: CD80 engages Hsp90ab1 at residue K69, which activates LRP5/β-catenin signaling to promote cytoskeletal reorganization and glomerulosclerosis, with β-catenin feeding back to sustain CD80 expression.

    Evidence LC-MS/MS proteomics, K69 site-directed mutagenesis of Hsp90ab1, B7-1 transgenic and adriamycin nephropathy mouse models, co-immunoprecipitation

    PMID:35710882

    Open questions at the time
    • Single-lab finding; independent replication of the Hsp90ab1–K69 interaction needed
    • Whether this pathway operates in human podocyte disease not confirmed
    • Structural basis for CD80–Hsp90ab1 interaction not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the NK cell receptor that recognizes CD80 independently of CD28/CTLA-4, the atomic structure of the PD-L1/CD80 cis complex, the mechanism by which CD80 versus CD86 differentially skew Th1/Th2 responses, and whether B cell-intrinsic CD80 signaling proceeds through distinct pathways from B cell-intrinsic CD86 signaling.
  • NK receptor for CD80 not identified
  • PD-L1/CD80 cis complex structure not solved
  • Mechanism of Th1/Th2 differential skewing by CD80 vs CD86 unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098631 cell adhesion mediator activity 3
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-168256 Immune System 8 R-HSA-1500931 Cell-Cell communication 4 R-HSA-162582 Signal Transduction 4
Partners
BCL6CD274CD28CD86CTLA4HSP90AB1LRP5
Complex memberships
CD80 homodimerCD80/CTLA-4 zipper-like latticecis CD80/PD-L1 complex

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CD80 (B7) was identified as a type I transmembrane glycoprotein of the immunoglobulin superfamily, with two extracellular Ig-like domains (one V-like, one C-like), expressed on activated B cells and B cell malignancies, functioning as a costimulatory ligand for T cells. cDNA cloning, expression in COS cells, immunoprecipitation, Northern blot Journal of immunology High 2794510
1991 CD80 (B7) delivers a costimulatory signal to T cells through direct binding to CD28, stimulating T cell proliferation and IL-2 mRNA accumulation; CD28-Ig fusion protein bound CD80 with Kd ~200 nM, and B7-transfected CHO cells costimulated T cell activation. Fusion protein binding assay (125I-labeled B7-Ig), CD28-transfected CHO cell binding, T cell proliferation assay, IL-2 mRNA measurement The Journal of experimental medicine High 1847722
1991 Murine CD80 (B7) was cloned; the predicted protein shares 44% amino acid identity with human B7 with conserved Ig-V and Ig-C domains; murine B7-transfected cells provided costimulatory signal to human CD28+ T lymphocytes, demonstrating conservation of the ligand attachment site. cDNA cloning, sequence analysis, transfection into CHO cells, T cell costimulation assay The Journal of experimental medicine High 1714935
1994 CD80 (B7-1) and CD86 (B7-2) are both ligands for CD28 and CTLA-4; both molecules are expressed on multiple APC types (B cells, T cells, macrophages, dendritic cells); their expression can be independently regulated by the same stimulus; blocking CD86 (B7-2) costimulatory activity inhibits TCR-dependent T cell proliferation and cytokine production without affecting early TCR signals (CD69, IL-2Rα induction). Flow cytometry, blocking antibody experiments, T cell proliferation and cytokine production assays The Journal of experimental medicine High 7519245
1994 The extracellular V-like domains of CD80 (B7-1) and CD86 (B7-2) share sequence similarities with MHC-encoded Ig superfamily members (butyrophilin, myelin/oligodendrocyte glycoprotein, chicken B-G), suggesting an evolutionary link between B7 molecules and MHC-encoded costimulatory molecules. Sequence analysis, structural comparison Protein science Low 7527261
1994 The C-like domain of CD80 is structurally compatible with IgSF C-set structures (best recognized by β2-microglobulin of MHC Class I), while the N-terminal V-like domain is not compatible with known IgSF V-set structures; 11 of 17 conserved residues in the C-like domain of B7-1/B7-2 are not standard IgSF C-1 set consensus residues and cluster on the surface, suggesting they mediate protein-protein interactions. Inverse folding methodology, sequence comparison mapped onto β2-microglobulin structure Protein science Low 7535614
1994 Ligation of CD28 by monoclonal antibody (but not by its physiological ligand B7-1/CD80) stimulates p21ras and downstream Ras-dependent events (ERK2 activation, Raf-1 hyperphosphorylation); both anti-CD28 mAb and B7-1 activate cellular PTKs and induce Vav tyrosine phosphorylation, but only anti-CD28 mAb induces tyrosine phosphorylation of the Grb2-associated p36 protein, which correlates with p21ras activation. In vitro kinase assays, anti-phosphotyrosine immunoblotting, Ras activation assay, co-immunoprecipitation The Journal of experimental medicine Medium 7520466
1994 BCL6 directly represses CD80 transcription: BCL6 binds the CD80 promoter in vivo and suppresses NF-κB-mediated transcriptional activation induced by CD40 signaling; BCL6-deficient mice show increased CD80 expression on B cells, and BCL6 and CD80 expression are mutually exclusive in normal B cells. Chromatin immunoprecipitation (ChIP), reporter assays, B cell expression analysis in BCL6-knockout mice, Western blot The Journal of experimental medicine High 12860928
1995 CD80 (B7-1) and CD86 (B7-2) differentially activate the Th1/Th2 developmental pathways: blockade of B7-1 reduced EAE incidence and favored Th2 clone generation (mediating IL-4-dependent disease amelioration), while blockade of B7-2 increased EAE severity; thus, shared counterreceptors CD28 and CTLA-4 yield very different outcomes depending on which B7 ligand is engaged. In vitro T cell differentiation assays, in vivo EAE model with anti-B7 antibody treatment, cytokine profiling, adoptive transfer Cell High 7534215
1995 CD80 and CD86 provide similar costimulatory signals for T cell proliferation, cytokine production (IL-2, IFN-γ), and CTL generation; CTLA-4-Ig binds both ligands with higher affinity than CD28-Ig; blocking both ligands simultaneously is required to optimally inhibit CD28-dependent proliferation in allogeneic MLR. Stable transfectants, anti-CD3 proliferation assay, cytokine ELISA, CTL generation, CD28-Ig/CTLA-4-Ig binding assay Journal of immunology High 7527824
1996 CD80 (B7-1) functions as a triggering signal for NK cell-mediated cytotoxicity that overrides MHC class I protection; this NK cell triggering by B7-1 occurs even in the absence of CD28 and cannot be blocked by anti-CD28 or anti-CTLA-4 antibodies, indicating NK cells use receptors other than CD28/CTLA-4 to interact with B7-1. NK cell cytotoxicity assays with purified populations, blocking antibody experiments, CD28-knockout mouse NK cells Immunity High 8885864
1996 CD40 signaling induces CD80 expression through a pathway involving specific threonine residues (T227 and T234) in the CD40 cytoplasmic tail; cAMP synergizes with CD40 signaling to induce high-level CD80 expression; a distinct CD40 domain (with only six cytoplasmic amino acids) retains growth-inhibitory function but loses CD80 induction capacity, demonstrating at least two distinct CD40 signaling domains. Transfection of wild-type and mutant CD40 constructs into M12 B lymphoma, flow cytometry for CD80 expression, cAMP treatment Journal of immunology Medium 8816387
1996 The V domain of CD86 (but not CD80) is sufficient for CTLA-4 binding; insertion of two residues between the two Ig domains of CD80 decreased affinity for CTLA-4, while the same insertion in CD86 had no effect, demonstrating a fundamental structural difference between CD80 and CD86 in receptor recognition. Domain-swapping constructs, binding assays with CTLA-4 and CD28 Journal of immunology Medium 8609386
1997 CD80 binds both CD28 and CTLA-4 with low affinity and very fast kinetics: at 37°C, soluble CD80 binds CTLA-4 with Kd ~0.42 μM and CD28 with Kd ~4 μM, with very fast dissociation rate constants (koff ≥ 0.43 s⁻¹ for CTLA-4 and ≥ 1.6 s⁻¹ for CD28), as measured by surface plasmon resonance. Surface plasmon resonance (BIAcore) with soluble recombinant proteins at physiological temperature The Journal of experimental medicine High 9053440
1998 CTLA-4 can potently inhibit T cell activation in the absence of CD28 through B7-1 engagement: CD28-deficient T cells primed with antigen-expressing tumor cells showed strong inhibition of cytokine production and proliferation when B7-1 was present on stimulators, and this inhibition was reversed by anti-B7-1 or anti-CTLA-4 antibodies, indicating CTLA-4 antagonizes TCR-mediated signals independent of CD28. TCR transgenic/RAG2-deficient/CD28 knockout mouse model, antigen-specific stimulation assays, antibody blocking The Journal of experimental medicine High 9653097
2000 The crystal structure of soluble B7-1 (sB7-1) at 3 Å resolution reveals a novel combination of two Ig-like domains: an IgV-like domain (characteristic of adhesion molecules) and an IgC-like domain (previously seen only in antigen receptors); sB7-1 forms parallel, 2-fold rotationally symmetric homodimers in the crystal lattice and also dimerizes in solution as demonstrated by analytical ultracentrifugation, suggesting avidity-enhanced binding to CTLA-4 homodimers favors stable inhibitory signaling complexes. X-ray crystallography (3 Å resolution), analytical ultracentrifugation Immunity High 10661405
2000 An alternatively spliced soluble form of porcine B7-1 (sB7-1) lacking both transmembrane and cytoplasmic domains was identified; porcine sB7-1-His interacted with both human CD28 and CTLA-4 and effectively blocked IL-2 production and T cell proliferation in response to porcine or human stimulator cells. cDNA cloning, Northern blot, His-tagged protein binding assay, T cell proliferation inhibition assay Journal of immunology Medium 10843688
2001 The crystal structure of the human CTLA-4/B7-1 complex at 3.0 Å resolution reveals: (1) an unusually high degree of shape complementarity at the binding interface; (2) CTLA-4 forms homodimers through a newly defined interface of highly conserved residues; (3) in the crystal lattice, bivalent CTLA-4 homodimers bridge bivalent B7-1 homodimers in a zipper-like oligomeric arrangement that provides the structural basis for unusually stable inhibitory signaling complexes. X-ray crystallography at 3.0 Å resolution Nature High 11279502
2001 The crystal structure of human CTLA-4/B7-2 complex at 3.2 Å shows that the unique dimerization properties of both CTLA-4 and B7-2 place ligand-binding sites distal to dimer interfaces, promoting alternating bivalent CTLA-4/B7-2 dimer networks throughout the crystal, providing a model for periodic organization within the immunological synapse. X-ray crystallography at 3.2 Å resolution Nature High 11279501
2001 Small molecules that inhibit CD80 binding to both CD28 and CTLA4 bind to the GFCC'C" face of the N-terminal V-set domain of human CD80; both classes of compounds appear to bind the same site, which is not present in homologous B7-2 or mouse B7-1, defining a species- and paralog-specific hot spot on CD80. Small molecule screening, competitive binding assay, domain mapping The Journal of biological chemistry Medium 11741888
2001 Naive CD4+ T cells acquire CD80 (B7-1) protein from syngeneic APCs after activation; this acquisition is CD28-dependent (absent in CD28-KO T cells), does not involve CD80 mRNA expression in T cells, is proportional to both signal 1 strength and APC CD80 level, and does not occur for other APC molecules (e.g., CD40); T cells that acquire CD80 can themselves act as APCs, while memory T cells that acquire CD80 undergo apoptosis in the presence of strong TCR signals. CD80/CD86 knockout mouse B cells as APC source, cyclohexamide treatment, confocal microscopy, CD28-KO T cells, RT-PCR for CD80 mRNA Journal of immunology High 11160311
2002 CD80 binds CTLA-4 and CD28 with higher affinity than CD86; relative to its CTLA-4 binding affinity, CD86 binds CD28 2-3 fold more effectively than CD80; unlike CD80, CD86 does not self-associate; CD28 homodimers are monovalent (not bivalent as previously assumed); CD80 markedly favors CTLA-4 over CD28 engagement, while CD86 exhibits much less bias, explaining their overlapping but distinct T cell response outcomes. Surface plasmon resonance, analytical ultracentrifugation, recombinant protein binding assays Immunity High 12196291
2003 B7-1 and B7-2 exist in different oligomeric states on the cell surface: B7-1 (CD80) is present as a dimer while B7-2 (CD86) exists as a monomer, as demonstrated by photobleaching-based FRET; B7-1 and B7-2 do not form hetero-oligomers on the cell surface. Fluorescence resonance energy transfer (FRET) via photobleaching on live cells Immunology letters Medium 16413062
2004 Ligation of B7-1/B7-2 on dendritic cells by CTLA4/CD28 expressed on CD4+ T cells is required to trigger functional IDO (indoleamine 2,3-dioxygenase) activity; IDO protein is constitutively expressed but requires this B7-1/B7-2 engagement signal to become functionally active; the ability to trigger IDO was strictly confined to CD4+ T cells, allowing them to dominantly inhibit CD8+ T cell proliferation via IDO-conditioned DCs. IDO activity assays, blocking antibody experiments (anti-B7-1/B7-2), direct B7-1/B7-2 crosslinking, T cell subset depletion experiments Journal of immunology High 15034022
2004 B7-1 (CD80) is expressed in podocytes upon injury and acts as an inducible modifier of glomerular permselectivity; LPS signaling through TLR-4 reorganizes the podocyte actin cytoskeleton in vitro; activation of B7-1 in cultured podocytes leads to reorganization of slit diaphragm proteins; mice lacking B7-1 are protected from LPS-induced nephrotic syndrome, establishing a non-immune cell role for CD80 in barrier function. B7-1 knockout mouse model, LPS treatment in vivo, in vitro podocyte culture with actin cytoskeleton analysis, immunofluorescence for slit diaphragm proteins The Journal of clinical investigation High 15146236
2009 Direct B7-1/2 signaling in B cells enhances IgG secretion: B7-2 engagement on already class-switched B cells dramatically induced IgG (but not IgM) secretion and induced XBP-1 splicing (a marker of increased protein synthesis); in vivo, B7-1/2 expression on B cells is crucial for maximal local IgG responses to influenza infection, demonstrated in mixed bone marrow chimeras lacking B7-1/2 only on B cells. Mixed bone marrow irradiation chimeric mice, in vitro B7-2 crosslinking, XBP-1 splicing assay (RT-PCR), antibody ELISA Journal of immunology High 19933871
2011 CTLA-4 removes CD80 and CD86 from opposing cells by trans-endocytosis: CTLA-4-expressing cells capture CD80/CD86 from antigen-presenting cells, and these costimulatory ligands are subsequently degraded inside the CTLA-4-expressing cells; CD86 acquisition is stimulated by TCR engagement and observed both in vitro and in vivo; this depletion of ligands impairs CD28 costimulation. Co-culture assays with CTLA-4-expressing cells, flow cytometry tracking ligand loss, intracellular degradation assays, in vivo confirmation Science High 21474713
2014 CD80 expression in CTCL cells is strictly dependent on STAT5a and STAT5b transcription factors: in IL-2-dependent CTCL cells, IL-2 induces CD80 in a Jak1/3- and STAT5a/b-dependent manner; CTLA-4 engagement on T cells (via CD80 on CTCL cells) inhibits normal T cell proliferation, revealing a CD80-CTLA-4 axis as an immune evasion mechanism. STAT5a/b knockdown (siRNA), Jak inhibitor treatment, CTLA-4 mRNA transfection in T cells, co-culture proliferation assays Journal of immunology Medium 24523507
2018 PD-L1 binds to B7-1 (CD80) only in cis on the same cell surface, not in trans between two different cells; this cis interaction was demonstrated by NanoBiT proximity assays and cell-to-cell binding assays; PD-L1 and B7-1 interact when PD-L1 is flexible (via its 11-amino-acid stalk) and bind at a site competitive with PD-L1/PD-1 and B7-1/CD28 interactions; coexpression of PD-L1 and B7-1 occurs on tumor-infiltrating myeloid cells. NanoBiT proximity assay, cell-to-cell binding assays, ELISA with purified proteins, flow cytometry, competitive binding assays Cancer immunology research High 29871885
2019 CD80 (B7-1) on antigen-presenting cells interacts with PD-L1 in cis to disrupt PD-L1/PD-1 binding, thereby restricting PD-1 coinhibitory signaling during T cell activation; in knock-in mice where cis-PD-L1/CD80 interaction cannot occur, tumor immunity and autoimmune responses were greatly attenuated by PD-1, confirming that CD80 on APCs limits PD-1 signaling while promoting CD28-mediated costimulation. Knock-in mouse model (cis-interaction deficient), tumor immunity assays, autoimmune response measurement, cis-interaction biochemical assays Science High 31000591
2020 The PD-L1 binding site on B7-1 (mB7-1) maps to the dimer interface surface of B7-1, distal from the CTLA-4/CD28 recognition surface; CTLA-4 and CD28 do not directly compete with PD-L1 for binding to B7-1, but can disrupt the cis PD-L1:B7-1 complex by reorganizing B7-1 on the cell surface; mPD-L1 mutants with selective binding for either mB7-1 or mPD-1 were generated. Cell microarray and high-throughput FACS binding screen, site-directed mutagenesis of PD-L1 and B7-1, cis interaction assays with two independent approaches PloS one High 32497097
2022 B7-1 mediates podocyte injury and glomerulosclerosis through a signaling pathway involving Hsp90ab1 and LRP5/β-catenin: LC-MS/MS identified Hsp90ab1 as an anchor transmitting signals from B7-1 to β-catenin; molecular docking and mutant analysis identified residue K69 in the N-terminal domain of Hsp90ab1 as the key binding site for B7-1 to activate LRP5/β-catenin; B7-1 is itself a downstream target of β-catenin, creating a positive feedback loop. LC-MS/MS proteomics, molecular docking, site-directed mutagenesis (K69 in Hsp90ab1), B7-1 transgenic mouse model, adriamycin nephropathy model, co-immunoprecipitation, transcriptomic analysis Cell death and differentiation Medium 35710882
2008 Human B7-1 (CD80) interacts with human PD-L1 with affinity greater than that of B7-1 with CD28, but less than B7-1 with CTLA-4 or PD-L1 with PD-1; anti-PD-L1 antibodies were identified that can selectively block PD-L1 interactions with B7-1, PD-1, or both; PD-L1 is induced to higher levels on CD28high versus CD28low CD8+ T cells upon activation. Surface plasmon resonance (Biacore), blocking antibody characterization, flow cytometry Molecular immunology Medium 18585785

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of experimental medicine 4219 11015443
2013 Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature reviews. Immunology 2399 23470321
1995 B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1499 7534215
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2011 Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science (New York, N.Y.) 1407 21474713
1991 Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. The Journal of experimental medicine 1219 1847722
2010 Multiple common variants for celiac disease influencing immune gene expression. Nature genetics 801 20190752
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1994 Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. The Journal of experimental medicine 616 7519245
1989 B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. Journal of immunology (Baltimore, Md. : 1950) 526 2794510
2002 The interaction properties of costimulatory molecules revisited. Immunity 524 12196291
2004 Induction of B7-1 in podocytes is associated with nephrotic syndrome. The Journal of clinical investigation 471 15146236
2000 Local control of the immune response in the liver. Immunological reviews 460 10807504
1995 CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. Journal of immunology (Baltimore, Md. : 1950) 443 7527824
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1997 CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. The Journal of experimental medicine 435 9053440
2003 The role of PI3K in immune cells. Nature immunology 391 12660731
2011 Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nature genetics 387 21399635
2004 Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 378 15034022
2001 Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses. Nature 369 11279502
1991 Structure, expression, and T cell costimulatory activity of the murine homologue of the human B lymphocyte activation antigen B7. The Journal of experimental medicine 368 1714935
2019 Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses. Science (New York, N.Y.) 317 31000591
1993 Tyrosine kinase-stimulated guanine nucleotide exchange activity of Vav in T cell activation. Science (New York, N.Y.) 297 8484124
2013 Abatacept in B7-1-positive proteinuric kidney disease. The New England journal of medicine 294 24206430
2001 Structural basis for co-stimulation by the human CTLA-4/B7-2 complex. Nature 269 11279501
2013 Structure and interactions of the human programmed cell death 1 receptor. The Journal of biological chemistry 268 23417675
1997 Lck regulates Vav activation of members of the Rho family of GTPases. Molecular and cellular biology 264 9032261
1995 Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity 263 8777719
2012 Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nature genetics 257 22561518
2007 T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nature medicine 241 18026115
2004 CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 224 14978077
2007 Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. The Journal of infectious diseases 223 17703412
2012 Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population. American journal of human genetics 213 23000144
2000 Structure and dimerization of a soluble form of B7-1. Immunity 195 10661405
1996 Triggering of natural killer cells by the costimulatory molecule CD80 (B7-1). Immunity 195 8885864
2010 PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1. International immunology 192 20587542
2008 Interaction of human PD-L1 and B7-1. Molecular immunology 191 18585785
2001 Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. The Journal of biological chemistry 180 11726649
2012 Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians. American journal of human genetics 173 23273568
1995 A reassessment of the role of B7-1 expression in tumor rejection. The Journal of experimental medicine 173 7595212
2018 PD-L1 Binds to B7-1 Only In Cis on the Same Cell Surface. Cancer immunology research 157 29871885
1994 The role of p21ras in CD28 signal transduction: triggering of CD28 with antibodies, but not the ligand B7-1, activates p21ras. The Journal of experimental medicine 155 7520466
2001 The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 147 11350882
2001 Effects of survivin antagonists on growth of established tumors and B7-1 immunogene therapy. Journal of the National Cancer Institute 145 11604477
1998 B7-1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28. The Journal of experimental medicine 135 9653097
1997 Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression. Proceedings of the National Academy of Sciences of the United States of America 135 9380730
1995 Role of B7-1 in mediating an immune response to myeloid leukemia cells. Blood 119 7537118
2006 Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma. Cancer research 116 16489051
1996 IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: enhancement by simultaneous B7-1 expression. Journal of immunology (Baltimore, Md. : 1950) 112 8617961
2014 Role of podocyte B7-1 in diabetic nephropathy. Journal of the American Society of Nephrology : JASN 110 24676639
1996 Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes. Immunology 110 9014827
1995 Costimulation with B7-1, IL-6, and IL-12 is sufficient for primary generation of murine antitumor cytolytic T lymphocytes in vitro. Journal of immunology (Baltimore, Md. : 1950) 108 7538528
2006 Enhanced antitumor effect of oncolytic adenovirus expressing interleukin-12 and B7-1 in an immunocompetent murine model. Clinical cancer research : an official journal of the American Association for Cancer Research 107 17020994
1996 B7-1 but not B7-2 efficiently costimulates CD8+ T lymphocytes in the P815 tumor system in vitro. Journal of immunology (Baltimore, Md. : 1950) 107 8543795
2010 Clinical significance of B7-H1 and B7-1 expressions in pancreatic carcinoma. World journal of surgery 106 20145927
2005 Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. The Journal of clinical investigation 104 15937544
2001 Anti-B7-1 blocks mononuclear cell adherence in vasa recta after ischemia. Kidney international 102 11576355
2005 B7-1 and B7-2: similar costimulatory ligands with different biochemical, oligomeric and signaling properties. Immunology letters 94 16413062
1996 Irradiated B7-1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML. Blood 91 8639914
2003 Muscle fibres and cultured muscle cells express the B7.1/2-related inducible co-stimulatory molecule, ICOSL: implications for the pathogenesis of inflammatory myopathies. Brain : a journal of neurology 90 12690043
2009 B7-1/2 (CD80/CD86) direct signaling to B cells enhances IgG secretion. Journal of immunology (Baltimore, Md. : 1950) 87 19933871
2006 Concurrent delivery of GM-CSF and B7-1 using an oncolytic adenovirus elicits potent antitumor effect. Gene therapy 85 16525479
1998 Presentation of proteolipid protein epitopes and B7-1-dependent activation of encephalitogenic T cells by IFN-gamma-activated SJL/J astrocytes. Journal of immunology (Baltimore, Md. : 1950) 84 9574529
2008 Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 82 18676757
1997 Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. Hepatology (Baltimore, Md.) 82 9141426
2001 Acquisition of CD80 (B7-1) by T cells. Journal of immunology (Baltimore, Md. : 1950) 81 11160311
2003 BCL6 controls the expression of the B7-1/CD80 costimulatory receptor in germinal center B cells. The Journal of experimental medicine 78 12860928
1996 Costimulation by CD48 and B7-1 induces immunity against poorly immunogenic tumors. The Journal of experimental medicine 78 8627175
2001 In situ expression of soluble B7-1 in the context of oncolytic herpes simplex virus induces potent antitumor immunity. Cancer research 76 11196154
1994 A negative regulatory function of B7 revealed in B7-1 transgenic mice. Immunity 74 7533646
1995 Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse. Diabetes 68 7533734
1994 Extending the B7 (CD80) gene family. Protein science : a publication of the Protein Society 66 7527261
2003 A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection. Journal of immunology (Baltimore, Md. : 1950) 60 12759417
1997 Effects of blocking B7-1 and B7-2 interactions during a type 2 in vivo immune response. Journal of immunology (Baltimore, Md. : 1950) 60 9126967
1999 Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells. Cancer gene therapy 59 10078962
1998 Absence of B7.1-CD28/CTLA-4-mediated co-stimulation in human NK cells. European journal of immunology 59 9541571
1998 Upregulation of B7.2, but not B7.1, on B cells from patients with allergic asthma. The Journal of allergy and clinical immunology 58 9449507
2001 Large nontransplanted hepatocellular carcinoma in woodchucks: treatment with adenovirus-mediated delivery of interleukin 12/B7.1 genes. Journal of the National Cancer Institute 56 11259473
2000 Costimulation by B7-1 and B7-2 is required for autoimmune disease in MRL-Faslpr mice. Journal of immunology (Baltimore, Md. : 1950) 56 10820290
2019 Targeting B7-1 in immunotherapy. Medicinal research reviews 55 31448437
1994 T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28. Blood 55 7513205
1997 The role of B7-1 and LFA-3 in costimulation of CD8+ T cells. Journal of immunology (Baltimore, Md. : 1950) 54 8992978
1996 Interactions of CD80 and CD86 with CD28 and CTLA4. Journal of immunology (Baltimore, Md. : 1950) 53 8609386
2011 IL-10-conditioned dendritic cells prevent autoimmune diabetes in NOD and humanized HLA-DQ8/RIP-B7.1 mice. Clinical immunology (Orlando, Fla.) 52 21458378
2000 gamma-ray irradiation induces B7.1 expression in myeloid leukaemic cells. British journal of haematology 52 10792289
1997 Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1. Gene therapy 50 9282170
1998 B7.1 is a quantitatively stronger costimulus than B7.2 in the activation of naive CD8+ TCR-transgenic T cells. Journal of immunology (Baltimore, Md. : 1950) 47 9820499
1994 Keratinocyte expression of B7-1 in transgenic mice amplifies the primary immune response to cutaneous antigens. Proceedings of the National Academy of Sciences of the United States of America 46 7528926
2015 Any value of podocyte B7-1 as a biomarker in human MCD and FSGS? American journal of physiology. Renal physiology 44 26697986
1998 Tissue-specific up-regulation of B7-1 expression and function during the course of murine relapsing experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md. : 1950) 44 9647224
2011 Host APCs augment in vivo expansion of donor natural regulatory T cells via B7H1/B7.1 in allogeneic recipients. Journal of immunology (Baltimore, Md. : 1950) 41 21263067
2014 Abatacept in B7-1-positive proteinuric kidney disease. The New England journal of medicine 40 24670178
1999 The modulation of B7.2 and B7.1 on B cells by immunosuppressive agents. Clinical and experimental immunology 40 10540152
2000 Primary structure and functional characterization of a soluble, alternatively spliced form of B7-1. Journal of immunology (Baltimore, Md. : 1950) 39 10843688
2001 Small molecule ligands define a binding site on the immune regulatory protein B7.1. The Journal of biological chemistry 38 11741888
2020 PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies. Trends in molecular medicine 37 33199209
1998 Effects of in vivo administration of anti-B7-1/B7-2 monoclonal antibodies on murine acute myocarditis caused by coxsackievirus B3. Circulation research 36 9529166
1998 The threshold for autoimmune T cell killing is influenced by B7-1. European journal of immunology 36 9541590
1996 Differential expression of the costimulatory molecules B7.1 (CD80) and B7.2 (CD86) in rheumatoid synovial tissue. British journal of rheumatology 36 8624620
1997 Treatment with intact anti-B7-1 mAb during disease remission enhances epitope spreading and exacerbates relapses in R-EAE. Journal of neuroimmunology 35 9394783
1996 Identification of distinct domains in CD40 involved in B7-1 induction or growth inhibition. Journal of immunology (Baltimore, Md. : 1950) 34 8816387
1994 Exaggerated and persistent cutaneous delayed-type hypersensitivity in transgenic mice whose epidermal keratinocytes constitutively express B7-1 antigen. The Journal of clinical investigation 34 7518845
1997 Irradiated NC adenocarcinoma cells transduced with both B7.1 and interleukin-2 induce CD4+-mediated rejection of established tumors. Human gene therapy 33 9054522
2012 Cancer immunotherapy using a membrane-bound interleukin-12 with B7-1 transmembrane and cytoplasmic domains. Molecular therapy : the journal of the American Society of Gene Therapy 32 22334018
1994 Immunoglobulin fold characteristics of B7-1 (CD80) and B7-2 (CD86). Protein science : a publication of the Protein Society 32 7535614
2015 B7-1 Is Not Induced in Podocytes of Human and Experimental Diabetic Nephropathy. Journal of the American Society of Nephrology : JASN 31 26319246
1998 Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in multiple sclerosis. Journal of neuroimmunology 31 9628461
2009 Preferential use of B7.2 and not B7.1 in priming of vaccinia virus-specific CD8 T cells. Journal of immunology (Baltimore, Md. : 1950) 30 19234186
2003 Recovery from EAE is associated with decreased survival of encephalitogenic T cells in the CNS of B7-1/B7-2-deficient mice. European journal of immunology 30 12884869
2000 Interleukin-7/B7.1-encoding adenoviruses induce rejection of transplanted but not nontransplanted tumors. Cancer research 30 10676654
1998 Gamma-ray irradiation induces B7.1 costimulatory molecule neoexpression in various murine tumor cells. Cancer immunology, immunotherapy : CII 29 9690456
1997 Antigen-specific regression of established tumors induced by active immunization with irradiated IL-12- but not B7-1-transfected tumor cells. International immunology 29 9310829
1996 Coexpression of B7-1 and antigen blocks tolerance induction to antigen presented by resting B cells. Journal of immunology (Baltimore, Md. : 1950) 29 8757319
1999 Enhancement of B7-1 (CD80) expression on B-lymphoma cells by irradiation. Immunology 28 10233753
2020 Mechanistic dissection of the PD-L1:B7-1 co-inhibitory immune complex. PloS one 27 32497097
1997 Immune responsiveness to a murine mammary carcinoma modified to express B7-1, interleukin-12, or GM-CSF. Cancer gene therapy 27 9171934
1997 Gene therapy with B7.1 and GM-CSF vaccines in a murine AML model. Journal of pediatric hematology/oncology 27 9407942
1996 Induction of autologous tumor-specific cytotoxic T-lymphocyte activity against a human renal carcinoma cell line by B7-1 (CD8O) costimulation. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy 27 9147700
2022 B7-1 mediates podocyte injury and glomerulosclerosis through communication with Hsp90ab1-LRP5-β-catenin pathway. Cell death and differentiation 26 35710882
2001 Angiostatin enhances B7.1-mediated cancer immunotherapy independently of effects on vascular endothelial growth factor expression. Cancer gene therapy 26 11687895
1997 B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease. British journal of cancer 26 9365164
1995 B7-1 expression by a non-antigen presenting cell-derived tumor. Cancer research 26 7538898
2008 B7-1 and B7-2 differentially control peripheral homeostasis of CD4(+)CD25(+)Foxp3(+) regulatory T cells. Transplant immunology 25 18848987
1998 Potential role of B7-1 and CD28 molecules in immunosuppression in leprosy. Clinical and experimental immunology 25 9472661
2015 CTLA4-Ig in B7-1-positive diabetic and non-diabetic kidney disease. Diabetologia 24 26409459
2014 Cutaneous T cell lymphoma expresses immunosuppressive CD80 (B7-1) cell surface protein in a STAT5-dependent manner. Journal of immunology (Baltimore, Md. : 1950) 24 24523507
1999 Protein transfer of glycosyl-phosphatidylinositol (GPI)-modified murine B7-1 and B7-2 costimulators. Journal of immunotherapy (Hagerstown, Md. : 1997) 24 10546154
1997 Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model. Journal of immunology (Baltimore, Md. : 1950) 24 9379015
2021 Peptide Blocking CTLA-4 and B7-1 Interaction. Molecules (Basel, Switzerland) 23 33419027