Affinage

Showing CD80 — B7-1 is a alias.

CD80

T-lymphocyte activation antigen CD80 · UniProt P33681

Length
288 aa
Mass
33.0 kDa
Annotated
2026-06-09
100 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD80 (B7-1) is a cell-surface immunoglobulin-superfamily glycoprotein on antigen-presenting cells that controls T cell activation by engaging the costimulatory receptor CD28 and the inhibitory receptor CTLA-4 (PMID:9053440, PMID:9653097). Its extracellular region comprises two Ig-like domains and assembles into 2-fold symmetric homodimers that persist both in crystals and in solution, and live-cell FRET confirms that B7-1 exists predominantly as dimers at the cell surface—distinct from the monomeric B7-2 (PMID:10661405, PMID:16221763). CD80 binds CTLA-4 (Kd ~0.42 µM) more avidly than CD28 (Kd ~4 µM), with very fast dissociation kinetics, and bivalent CTLA-4 dimers bridge bivalent B7-1 dimers into a zipper-like oligomeric lattice that provides a structural basis for stable inhibitory signaling complexes (PMID:11279502, PMID:9053440). CD80 and CD86 engage CTLA-4 through similar but distinct determinants, and the CD80 inter-domain linker specifically contributes to CTLA-4 binding (PMID:7534620, PMID:8557978, PMID:8609386). CTLA-4 ligation of B7-1 inhibits T cell responses even in the complete absence of CD28, establishing an intrinsic inhibitory function independent of CD28 competition (PMID:9653097). Beyond these receptors, CD80 binds PD-L1 with intermediate affinity exclusively in cis on the same cell surface, through an interface mapping to the B7-1 dimer surface that overlaps the CTLA-4/PD-1 contacts; this cis interaction bidirectionally inhibits T cell activation and is required in vivo for PD-L1-mediated suppression of effector and alloreactive T cells (PMID:17629517, PMID:29871885, PMID:32497097, PMID:21697456, PMID:21697455). CD80 transcription is driven by NF-κB binding to a cell-type-specific enhancer ~3 kb upstream of the start site and is directly repressed in germinal-center B cells by BCL6 binding the promoter (PMID:8642282, PMID:12860928). CD80 also functions outside the immune synapse: it is induced in kidney podocytes via TLR4 signaling, where its activation reorganizes the actin cytoskeleton and disrupts slit-diaphragm proteins to produce proteinuria (PMID:15146236).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Establishing how CD80 transcription is controlled defined the cell-type-specific, signal-inducible logic of costimulator expression.

    Evidence DNase I hypersensitivity mapping, reporter assays, and EMSA identifying an upstream NF-κB-dependent enhancer in B7.1-positive B cells

    PMID:8642282

    Open questions at the time
    • Does not identify which NF-κB subunits drive the response in vivo
    • Upstream receptor signals feeding the enhancer not fully resolved
  2. 1994 Low

    Computational modeling first predicted CD80's two-Ig-domain architecture before any experimental structure existed.

    Evidence Inverse-folding prediction and conservation mapping onto β2-microglobulin

    PMID:7535614

    Open questions at the time
    • Prediction only; superseded by later crystal structures
    • No experimental validation of domain folds at the time
  3. 1994 High

    Comparing CD80 and CD86 binding to CD28/CTLA-4 showed the two ligands have distinct binding determinants and kinetics despite similar overall avidity, implying non-redundant roles.

    Evidence Cell-binding, competitive inhibition, and dissociation-kinetics assays with the CTLA-4 Y100A mutant

    PMID:7534620

    Open questions at the time
    • Structural basis of the differential determinants not resolved here
    • Functional consequence of slower CD80 dissociation in vivo unclear
  4. 1995 Medium

    Antibody blockade tested whether CD80 and CD86 differentially shape effector T cell fate, linking costimulator choice to Th1/Th2 polarization.

    Evidence In vivo EAE model with anti-B7-1/anti-B7-2 blockade, cytokine profiling, and anti-IL-4 co-treatment

    PMID:7534215

    Open questions at the time
    • Later contested by other groups
    • Mechanism by which B7-1 vs B7-2 biases cytokine output not defined
  5. 1996 Medium

    Mutagenesis dissected which CTLA-4 and CD80 residues control binding, mapping the differential recognition between the two B7 ligands.

    Evidence CTLA-4 MYPPPY point mutants and CD80/CD86 domain-swap/insertion constructs assayed by SPR and cell binding

    PMID:8557978 PMID:8609386

    Open questions at the time
    • Interface positions inferred from binding loss without co-structure
    • Quantitative kinetic effects of individual residues incomplete
  6. 1997 High

    Quantifying CD80 affinity and kinetics for both receptors showed low-affinity, fast-off interactions suited to dynamic T cell–APC contacts.

    Evidence Surface plasmon resonance at 37°C measuring Kd and koff for CTLA-4 and CD28

    PMID:9053440

    Open questions at the time
    • Does not address avidity effects of surface dimerization
    • Kinetics measured with soluble monomeric proteins
  7. 1998 High

    Genetic CD28 deletion plus antibody rescue established that CTLA-4 ligation by B7-1 inhibits T cells intrinsically, not merely by outcompeting CD28.

    Evidence TCR-transgenic/RAG2-deficient/CD28-knockout T cells stimulated with B7-1+ cells, reversed by anti-B7-1/anti-CTLA-4

    PMID:9653097

    Open questions at the time
    • Downstream CTLA-4 signaling effectors not defined
    • Physiological setting where CD28-independent inhibition dominates unclear
  8. 2000 High

    Solving the B7-1 ectodomain structure revealed it forms symmetric homodimers in crystal and solution, providing a physical basis for avidity-enhanced CTLA-4 engagement.

    Evidence X-ray crystallography at 3 Å and analytical ultracentrifugation

    PMID:10661405

    Open questions at the time
    • Dimer relevance on intact cell surface not yet shown
    • Stoichiometry of receptor complexes inferred, not directly observed
  9. 2001 High

    The CTLA-4/B7-1 co-crystal showed bivalent dimers bridging into a zipper-like lattice, explaining how stable inhibitory signaling complexes assemble.

    Evidence X-ray crystallography of the human CTLA-4/B7-1 complex at 3.0 Å

    PMID:11279502

    Open questions at the time
    • Lattice oligomerization not confirmed at native synapse density
    • Does not address CD28 complex geometry
  10. 2001 Medium

    Tracking CD80 protein transfer revealed that T cells acquire CD80 from APCs via a CD28-dependent route, conferring an immunoregulatory APC-like and pro-apoptotic phenotype.

    Evidence KO APC donors, cycloheximide, RT-PCR, CD28-KO controls, confocal imaging, and apoptosis assays

    PMID:11160311

    Open questions at the time
    • Molecular mechanism of trogocytosis not defined
    • In vivo prevalence and consequence of CD80 acquisition unclear
  11. 2003 High

    ChIP and KO mice identified BCL6 as a direct repressor of CD80 in germinal-center B cells, defining how NF-κB-driven CD80 induction is silenced during the GC reaction.

    Evidence ChIP of BCL6 at the CD80 promoter, reporter assays, and BCL6-deficient mice

    PMID:12860928

    Open questions at the time
    • Co-repressor machinery recruited by BCL6 not specified
    • Reversal of repression upon GC exit not mapped
  12. 2003 Medium

    Genetic dissection placed B7-1/B7-2 in thymic negative selection, showing CD28 and an additional co-receptor mediate B7-dependent clonal deletion.

    Evidence B7-1/B7-2 and CD28/CTLA-4 KO mice in an endogenous superantigen deletion model

    PMID:12759417

    Open questions at the time
    • Identity of the additional B7-binding co-receptor unknown
    • Quantitative contribution of B7-1 vs B7-2 not separated
  13. 2004 Medium

    Functional assays showed B7-1/B7-2 ligation by T cell CTLA-4/CD28 is obligatory to activate constitutively expressed IDO in DCs, revealing reverse signaling that drives tolerance.

    Evidence IDO enzymatic assays with anti-B7 blocking and cross-linking antibodies in human DCs

    PMID:15034022

    Open questions at the time
    • Intracellular signaling pathway from B7 to IDO not defined
    • Single lab, in vitro human DC system
  14. 2004 Medium

    KO mice and podocyte cultures uncovered a non-immune, cell-intrinsic CD80 function in the kidney, where TLR4-driven induction disrupts the slit diaphragm and causes proteinuria.

    Evidence B7-1-knockout LPS nephrosis model, SCID mice, and cultured podocyte actin/slit-diaphragm assays

    PMID:15146236

    Open questions at the time
    • Some findings contested by later studies
    • Downstream effector linking B7-1 to cytoskeletal reorganization unclear
  15. 2005 High

    Live-cell FRET validated the crystallographic dimer interface, confirming B7-1 is dimeric (and B7-2 monomeric) on intact cells, with implications for synapse geometry.

    Evidence Photobleaching-based FRET plus dimer-interface mutagenesis on intact cells

    PMID:16221763

    Open questions at the time
    • Functional consequence of distinct B7-1/B7-2 geometry in synapse not directly tested
    • Dimer dynamics during receptor engagement not measured
  16. 2006 Medium

    Identifying MCMV m138 as a B7-1-degrading viral protein demonstrated that pathogens target CD80 to subvert CD8 T cell priming.

    Evidence Mutant MCMV gene identification, biochemical fractionation, imaging of lysosomal rerouting, and CD8 T cell activation assays

    PMID:17142739

    Open questions at the time
    • Direct m138–B7-1 binding interface not mapped
    • Single lab; in vivo immune-evasion contribution not quantified
  17. 2007 High

    Discovery of the PD-L1:B7-1 interaction added a third receptor axis, with genetic epistasis showing this pair bidirectionally inhibits T cells.

    Evidence Binding affinity measurements and functional assays with PD-1/B7-1 and CD28/CTLA-4 multi-KO T cells

    PMID:17629517

    Open questions at the time
    • Cis vs trans orientation not resolved at this stage
    • Structural interface not directly determined
  18. 2009 Medium

    B cell chimeras and in vitro engagement showed B7-1/B7-2 reverse signaling enhances IgG secretion via XBP-1 activation, a B-cell-intrinsic role independent of GC formation.

    Evidence Mixed bone marrow chimeras, in vitro B7-2 engagement, IgG/IgM ELISA, and XBP-1 splicing assay

    PMID:19933871

    Open questions at the time
    • Signaling cascade from B7 cytoplasmic tail to XBP-1 not defined
    • Relative roles of B7-1 vs B7-2 not separated
  19. 2011 High

    In vivo blockade with selective anti-PD-L1 antibodies and B7-1-deficient recipients established that the PD-L1:B7-1 axis is required for PD-L1-mediated suppression of effector and alloreactive T cells.

    Evidence NOD diabetes and bm12→B6 heart transplant models with selective vs dual anti-PD-L1 mAbs and B7.1-/B7.2-KO recipients

    PMID:21697455 PMID:21697456

    Open questions at the time
    • Directionality (DC vs T cell) mechanism not fully resolved
    • Did not yet establish whether the interaction was cis or trans
  20. 2018 High

    Multiple orthogonal binding assays established that PD-L1 binds B7-1 only in cis on the same cell, redefining the geometry of the interaction and explaining how cis PD-L1 sequesters B7-1 from CD28.

    Evidence Cell-to-cell binding, ELISA, flow cytometry, and NanoBiT proximity assays

    PMID:29871885

    Open questions at the time
    • Precise interface residues not mapped in this study
    • Quantitative impact on synaptic CD28 engagement not measured
  21. 2020 High

    Interface mapping localized the PD-L1 binding site to the B7-1 dimer surface, distal from CTLA-4/CD28 sites, and showed CTLA-4/CD28 can disrupt cis PD-L1:B7-1 by reorganizing B7-1.

    Evidence Cell-microarray FACS binding screen and site-directed mutagenesis of PD-L1 and B7-1 with two independent cis-binding assays

    PMID:32497097

    Open questions at the time
    • Co-structure of the cis complex not determined
    • Dynamics of B7-1 reorganization at the synapse not directly imaged

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple CD80 receptor axes (CD28, CTLA-4, cis PD-L1) are spatially partitioned and dynamically balanced within a single immunological synapse, and what intracellular reverse-signaling effectors couple CD80 ligation to outcomes in DCs and B cells, remain unresolved.
  • No integrated structural/imaging model of competing CD80 complexes at the native synapse
  • Cytoplasmic signaling machinery for B7-1 reverse signaling unidentified
  • Effector linking podocyte B7-1 to cytoskeletal disruption undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
BCL6CD274CD28CTLA4

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Crystal structure of the human CTLA-4/B7-1 complex resolved at 3.0 Å. CTLA-4 forms homodimers through a conserved interface, and B7-1 also forms homodimers; in the crystal lattice, bivalent CTLA-4 homodimers bridge bivalent B7-1 homodimers in a zipper-like oligomeric arrangement, providing structural basis for unusually stable inhibitory signaling complexes. The CTLA-4/B7-1 binding interface shows high shape complementarity. X-ray crystallography (3.0 Å resolution) Nature High 11279502
2000 Crystal structure of the extracellular region of B7-1 (sB7-1) solved at 3 Å resolution reveals a novel combination of two Ig-like domains (one adhesion-type, one antigen-receptor-type). sB7-1 forms parallel, 2-fold rotationally symmetric homodimers in the crystal lattice and also dimerizes in solution (confirmed by analytical ultracentrifugation), suggesting avidity-enhanced binding to CTLA-4 homodimers favors formation of stable inhibitory signaling complexes. X-ray crystallography (3 Å) and analytical ultracentrifugation Immunity High 10661405
1997 Surface plasmon resonance at 37°C showed CD80 binds CTLA-4 with Kd ~0.42 µM and CD28 with Kd ~4 µM, both with very fast dissociation rate constants (koff ≥0.43 s⁻¹ for CTLA-4 and ≥1.6 s⁻¹ for CD28). These low affinities result from rapid kinetics, analogous to T cell adhesion molecules, potentially accommodating dynamic T cell–APC contacts. Surface plasmon resonance (Biacore) binding kinetics The Journal of experimental medicine High 9053440
1994 CD80 (B7-1) and CD86 (B7-2) bind CD28 and CTLA-4 with similar overall avidity (~2–3-fold difference), but CD80 binds the CTLA-4 mutant Y100A >200-fold better than CD86, CD80-CTLA4Ig complexes dissociate 5–8-fold more slowly, and inhibition of CD80-mediated responses requires ~100-fold lower CTLA4Ig concentrations, demonstrating distinct binding determinants and kinetics for CD80 vs. CD86. Cell binding assays, competitive inhibition assays, CTLA4Ig mutant Y100A binding, dissociation kinetics Immunity High 7534620
2005 Using photobleaching-based FRET (pbFRET) on live cells, B7-1 exists predominantly as dimers on the cell surface, whereas B7-2 exists as monomers. Mutations in B7-1 at the crystallographic dimer interface convert it to a predominantly monomeric species on the cell surface, validating the crystallographic dimer interface and suggesting B7-1 and B7-2 adopt different geometric organizations in the immunological synapse. Photobleaching-based FRET (pbFRET) on intact cells; site-directed mutagenesis of dimer interface Proceedings of the National Academy of Sciences of the United States of America High 16221763
2007 B7-1 (CD80) and PD-L1 interact with affinity intermediate between B7-1:CD28 and B7-1:CTLA-4 interactions. The PD-L1:B7-1 interface overlaps with the B7-1:CTLA-4 and PD-L1:PD-1 interfaces. This interaction inhibits T cell activation and cytokine production. Genetic evidence using PD-1-deficient vs. PD-1,B7-1 double-deficient T cells and CD28,CTLA-4 double-deficient vs. triple-deficient T cells demonstrated that PD-L1 and B7-1 interact specifically to bidirectionally inhibit T cell activation. Binding affinity measurements, genetic double/triple-KO T cell functional assays, cytokine production assays Immunity High 17629517
2018 PD-L1 binds B7-1 only in cis (on the same cell surface), not in trans between two cells. Cell-to-cell binding assays showed PD-L1-transfected cells did not bind B7-1-transfected cells. By ELISA and flow cytometry, PD-L1 and B7-1 interact strongly only when PD-L1 is flexible. NanoBiT proximity assays directly demonstrated cis binding on the same cell surface. Soluble PD-1 and B7-1 competed for binding to PD-L1, and cis PD-L1:B7-1 interaction can block B7-1 binding to CD28. Cell-to-cell binding assay, ELISA with purified proteins, flow cytometry, NanoBiT proximity ligation assay Cancer immunology research High 29871885
2020 Mutagenesis mapping showed that the PD-L1 binding site on mB7-1 maps to the dimer interface surface of B7-1, distal from the CTLA-4/CD28 recognition surface. Although CTLA-4 and CD28 do not directly compete with PD-L1 for binding to B7-1, they can disrupt the cis PD-L1:B7-1 complex by reorganizing B7-1 on the cell surface. mPD-L1 and mB7-1 were confirmed to bind in cis using two independent approaches. Cell microarray and high-throughput FACS binding screen; site-directed mutagenesis of PD-L1 and B7-1; two independent cis-binding assays PloS one High 32497097
1996 CTLA-4 substitutions in the MYPPPY domain differentially affect CD80 vs. CD86 binding: five single amino acid substitutions in the MYPPPY region had modest effects on CD80 binding but completely abrogated CD86 binding. CD80 and CD86 also showed different association/dissociation kinetics to CTLA-4 by surface plasmon resonance, demonstrating they bind similar but distinct sites on CTLA-4. Surface plasmon resonance; CTLA-4 point mutants tested by cell binding; competitive binding assays Journal of immunology High 8557978
1996 A cell-type-specific enhancer approximately 3 kb upstream of the human B7.1 transcription start site was identified. This 183-bp region is both cell-type specific and inducible by LPS and dibutyryl cAMP. Site-directed mutagenesis revealed an NF-κB consensus sequence as a functionally critical cis-element; NF-κB family members in B7.1-positive B cells bind this element in vivo, linking NF-κB signaling to B7.1 transcriptional induction. DNase I hypersensitivity mapping, luciferase reporter assays, deletional and site-directed mutagenesis, EMSA/gel shift for NF-κB binding The Journal of experimental medicine High 8642282
2003 BCL6 directly represses CD80 (B7-1) expression in germinal center B cells. CD40 signaling induces CD80 transcription via NF-κB, and BCL6 prevents this by binding the CD80 promoter region in vivo and suppressing NF-κB-mediated transcriptional activation. BCL6-deficient mice show increased CD80 expression in B cells, and CD80 and BCL6 expression are mutually exclusive in B cells. ChIP (BCL6 binding to CD80 promoter in vivo), luciferase reporter assays, BCL6 knockout mice, flow cytometry The Journal of experimental medicine High 12860928
2004 Ligation of B7-1/B7-2 on dendritic cells by CTLA-4/CD28 on T cells is obligately required to trigger functional IDO activity. IDO protein is constitutively expressed but remains inactive unless B7-1/B7-2 are engaged; disruption of this interaction keeps IDO inactive and prevents DC-mediated T cell suppression. Direct antibody-mediated cross-linking of B7-1/B7-2 fully restores IDO activation. Only CD4+ T cells (not CD8+) can trigger IDO induction. IDO enzymatic activity assay in DCs; T cell proliferation inhibition assay; anti-B7 blocking antibodies; B7 cross-linking antibodies Journal of immunology Medium 15034022
2004 B7-1 (CD80) is induced in podocytes by LPS (via TLR4 signaling) and in multiple experimental and genetic kidney disease models. In vivo, LPS rapidly upregulates podocyte B7-1 causing nephrotic-range proteinuria in WT and SCID mice. B7-1-knockout mice are protected from LPS-induced nephrotic syndrome. In cultured podocytes, B7-1 activation reorganizes actin cytoskeleton and disrupts slit diaphragm proteins, revealing a non-immune cell-intrinsic function of B7-1 in modifying glomerular permselectivity. B7-1 knockout mice (in vivo LPS model); cultured podocyte B7-1 activation (in vitro actin/slit diaphragm assays); LPS challenge in SCID mice The Journal of clinical investigation Medium 15146236
2006 MCMV protein m138 (fcr-1) targets B7-1 in the secretory pathway and reroutes it to LAMP-1+ lysosomal compartments, causing rapid disappearance of B7-1 from the DC cell surface. m138-expressing DCs have impaired ability to activate CD8+ T cells, identifying m138 as the first viral protein that specifically targets B7-1 for degradation. Viral gene identification by mutant MCMV; biochemical fractionation; immunocytochemistry; CD8+ T cell activation assay Journal of immunology Medium 17142739
2001 Naive CD4+ T cells acquire CD80 (B7-1) protein from syngeneic APCs after activation via a CD28-dependent mechanism (not endogenous synthesis, as confirmed by cycloheximide treatment and absence of CD80 mRNA in acquiring T cells). T cells that acquire CD80 can themselves act as APCs. Memory T cells that acquire CD80 undergo apoptosis when given increased TCR signal 1, revealing an immunoregulatory function. CD80/CD86 knockout APC donors; cycloheximide treatment; RT-PCR for CD80 mRNA; CD28-KO mice (negative control); confocal microscopy; functional APC assay; apoptosis assay Journal of immunology Medium 11160311
1998 B7-1 engagement of CTLA-4 inhibits T cell activation in the absence of CD28, demonstrating that CTLA-4 can antagonize TCR-mediated signaling independently of competing with CD28. TCR-transgenic/RAG2-deficient/CD28-knockout T cells responded to B7-1-expressing stimulator cells with inhibition rather than costimulation; this inhibition was reversed by anti-B7-1 or anti-CTLA-4 mAb. TCR transgenic/RAG2-deficient/CD28-knockout mice; tumor stimulator cells with/without B7-1; anti-B7-1 and anti-CTLA-4 blocking antibodies; cytokine and proliferation assays The Journal of experimental medicine High 9653097
2011 The PD-L1:B7-1 interaction inhibits diabetogenic effector T cell responses in vivo. Anti-PD-L1 mAb 10F.2H11, which selectively blocks only PD-L1:B7-1 (not PD-L1:PD-1), accelerated diabetes in older NOD mice and in adoptive transfer with effector (but not prediabetic) T cells. Dual-blocker anti-PD-L1 mAb was effective in all settings. PDL1 blockade failed to accelerate rejection in B7.1-deficient recipients, confirming that PDL1 inhibition depends on its interaction with B7-1 in vivo. NOD mouse diabetes model; selective blocking anti-PD-L1 mAbs; B7.1-deficient recipients; adoptive T cell transfer; diabetes incidence readout Journal of immunology High 21697456
2011 In a heart transplant model, PDL1 blockade accelerated allograft rejection in B7.2-deficient but not B7.1-deficient recipients, demonstrating that PDL1:B7-1 interaction is required for PDL1-mediated inhibition of alloimmune responses in vivo. In vitro, blockade of PDL1 on dendritic cells (interacting with T cell B7-1) increased alloreactive CD4+ T cell IFN-γ production, while blocking DC B7-1 interaction with T cell PDL1 did not, indicating a directional dominance of PDL1(DC):B7-1(T cell) interaction. bm12→B6 heart transplant model; B7.1-KO and B7.2-KO recipients; anti-PD-L1 mAbs with distinct blocking specificities; in vitro blocking assay with DCs and T cells; IFN-γ ELISA Journal of immunology High 21697455
2003 B7-1 and B7-2 participate in negative selection (clonal deletion) of thymocytes. Following endogenous superantigen-driven deletion in B7-1- and/or B7-2-deficient mice, deletion was impaired. Either CD28 or an additional undefined co-receptor can mediate B7-dependent deletion signals. CTLA-4 delivers inhibitory signals opposing CD28 during thymic selection. B7-1/B7-2 single and double KO mice; CD28-KO and CD28/CTLA-4 double-KO mice; endogenous superantigen deletion model (thymocyte flow cytometry) Journal of immunology Medium 12759417
2009 Direct signaling through B7-1/B7-2 on B cells (reverse signaling) enhances IgG secretion. Mixed bone marrow chimeric mice lacking B7-1/2 only on B cells had reduced local IgG responses after influenza infection without affecting germinal center formation or CD4+ T cell activation. In vitro, B7-2 engagement on class-switched B cells dramatically enhanced IgG (but not IgM) secretion and induced XBP-1/spliced XBP-1 expression, indicating increased protein synthesis/secretory pathway activation. Mixed bone marrow irradiation chimeras (B7-1/2-deficient B cells); in vitro B7-2 engagement on class-switched B cells; IgG/IgM ELISA; XBP-1 mRNA splicing assay; influenza infection model Journal of immunology Medium 19933871
1995 B7-1 and B7-2 costimulatory molecules differentially activate Th1 and Th2 developmental pathways. Anti-B7-1 treatment in EAE reduced disease incidence and shifted T cells toward Th2 (anti-IL-4 reversed this protection), while anti-B7-2 increased disease severity. Neither antibody affected overall T cell induction but altered cytokine profiles. In vivo EAE model; anti-B7-1 and anti-B7-2 antibody blockade; Th1/Th2 cytokine profiling; adoptive transfer; anti-IL-4 co-treatment Cell Medium 7534215
1994 A cell-type-specific enhancer in the human B7.1 gene is regulated by NF-κB. The 183-bp enhancer ~3 kb upstream of the transcription start site is active in B7.1-positive B cells, responsive to LPS and dibutyryl cAMP, and contains a functional NF-κB consensus element whose mutation abrogates activity. NF-κB family members bind this element in B7.1-positive B cells. DNase I hypersensitive site mapping; deletion and site-directed mutagenesis of reporter constructs; gel shift/EMSA assays The Journal of experimental medicine High 8642282
1994 The extracellular region of B7-1 contains two IgSF domains: an N-terminal V-like domain (whose fold is distinct from classical IgSF V-sets) and a C-like domain compatible with IgSF C-set structures and best recognized by β2-microglobulin. Conserved residues in B7 molecules cluster on the surface of the C-domain, potentially involved in interactions with the V-like domain or other molecules. Inverse folding methodology (computational structure prediction validated against known structures); sequence conservation analysis mapped onto β2m crystal structure Protein science Low 7535614
1996 Insertion of two residues between the two Ig domains of CD80 decreased affinity for CTLA-4, while a similar insertion in CD86 had no effect, demonstrating that the inter-domain linker of CD80 contributes to CTLA-4 binding. Additionally, the V-domain of CD86 (but not CD80) is sufficient for CTLA-4 binding, revealing a fundamental structural difference between the two ligands in their receptor recognition mechanism. CD80/CD86 mutant domain-swap and insertion constructs; cell-binding assays with CTLA-4 Journal of immunology Medium 8609386

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1500 7534215
2007 Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 1416 17629517
1994 Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 808 7534620
1994 Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. The Journal of experimental medicine 616 7519245
2004 Induction of B7-1 in podocytes is associated with nephrotic syndrome. The Journal of clinical investigation 471 15146236
1997 CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. The Journal of experimental medicine 438 9053440
1995 Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. The Journal of experimental medicine 385 7500044
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 371 11279502
1994 Regulation of immunostimulatory function and costimulatory molecule (B7-1 and B7-2) expression on murine dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 347 7514631
2013 Abatacept in B7-1-positive proteinuric kidney disease. The New England journal of medicine 294 24206430
1994 Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen. Journal of immunology (Baltimore, Md. : 1950) 240 7519638
2000 Structure and dimerization of a soluble form of B7-1. Immunity 195 10661405
1995 Distinct roles for B7-1 (CD-80) and B7-2 (CD-86) in the initiation of experimental allergic encephalomyelitis. The Journal of clinical investigation 174 7593605
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 160 29871885
2011 The programmed death-1 ligand 1:B7-1 pathway restrains diabetogenic effector T cells in vivo. Journal of immunology (Baltimore, Md. : 1950) 158 21697456
1995 CD28 ligands CD80 (B7-1) and CD86 (B7-2) induce long-term autocrine growth of CD4+ T cells and induce similar patterns of cytokine secretion in vitro. International immunology 146 7577797
1996 Does B7-1 expression confer antigen-presenting cell capacity to tumors in vivo? The Journal of experimental medicine 142 8642281
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
1996 Interleukin-12 and B7.1 co-stimulation cooperate in the induction of effective antitumor immunity and therapy of established tumors. European journal of immunology 135 8647214
1995 Coexpression of B7-1 and viral ("self") transgenes in pancreatic beta cells can break peripheral ignorance and lead to spontaneous autoimmune diabetes. Immunity 134 8777718
2003 Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. The Journal of experimental medicine 131 12847135
1995 Co-expression of B7-1 and ICAM-1 on tumors is required for rejection and the establishment of a memory response. European journal of immunology 131 7539748
1995 B7-1 and interleukin 12 synergistically induce effective antitumor immunity. Cancer research 128 7585539
2006 Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma. Cancer research 117 16489051
2011 The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. Journal of immunology (Baltimore, Md. : 1950) 114 21697455
1995 T-cell costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are expressed in human microglia but not in astrocytes in culture. Brain research 112 8750966
1996 Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes. Immunology 111 9014827
2014 Role of podocyte B7-1 in diabetic nephropathy. Journal of the American Society of Nephrology : JASN 110 24676639
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
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
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
2005 Different cell surface oligomeric states of B7-1 and B7-2: implications for signaling. Proceedings of the National Academy of Sciences of the United States of America 84 16221763
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
1995 Expression of B7-1 by highly metastatic mouse T lymphomas induces optimal natural killer cell-mediated cytotoxicity. Cancer research 78 7540948
1996 Costimulation of IL-4 production by murine B7-1 and B7-2 molecules. Journal of immunology (Baltimore, Md. : 1950) 75 8609397
1994 B7-1/CD80-transduced tumor cells elicit better systemic immunity than wild-type tumor cells admixed with Corynebacterium parvum. Cancer research 75 7522958
1994 A negative regulatory function of B7 revealed in B7-1 transgenic mice. Immunity 74 7533646
1998 Role of CD80 (B7.1) and CD86 (B7.2) in the immune response to an intracellular pathogen. Journal of immunology (Baltimore, Md. : 1950) 73 9469444
1995 Reciprocal expression of co-stimulatory molecules, B7-1 and B7-2, on murine T cells following activation. European journal of immunology 72 7531145
1997 Costimulatory signals through B7.1/CD28 prevent T cell apoptosis during target cell lysis. Journal of immunology (Baltimore, Md. : 1950) 70 9378968
1996 Expression and function of B7-1 (CD80) and B7-2 (CD86) on human epidermal Langerhans cells. European journal of immunology 70 8617317
1996 A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB. The Journal of experimental medicine 70 8642282
1995 Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse. Diabetes 68 7533734
1997 B7-1-dependent co-stimulation results in qualitatively and quantitatively different responses by CD4+ and CD8+ T cells. European journal of immunology 67 9079798
1994 Extending the B7 (CD80) gene family. Protein science : a publication of the Protein Society 66 7527261
1997 Expression of costimulatory molecules B7-1 and B7-2 by macrophages along invasive margin of colon cancer: a possible antitumor immunity? Laboratory investigation; a journal of technical methods and pathology 65 9314947
1996 Differential effects of CTLA-4 substitutions on the binding of human CD80 (B7-1) and CD86 (B7-2). Journal of immunology (Baltimore, Md. : 1950) 63 8557978
2003 A role for the B7-1/B7-2:CD28/CTLA-4 pathway during negative selection. Journal of immunology (Baltimore, Md. : 1950) 60 12759417
1999 Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. Cancer research 60 10344754
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
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
1998 The role of B7-1 and B7-2 costimulation for the generation of CTL responses in vivo. Journal of immunology (Baltimore, Md. : 1950) 58 9743331
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
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
2000 gamma-ray irradiation induces B7.1 expression in myeloid leukaemic cells. British journal of haematology 52 10792289
2006 Viral interference with B7-1 costimulation: a new role for murine cytomegalovirus fc receptor-1. Journal of immunology (Baltimore, Md. : 1950) 51 17142739
1995 B7-1 enhances natural killer cell-mediated cytotoxicity and inhibits tumor growth of a poorly immunogenic murine carcinoma. Cellular immunology 51 7553886
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
1995 A B7-1-transfected human melanoma line stimulates proliferation and cytotoxicity of autologous and allogeneic lymphocytes. European journal of immunology 47 7589065
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
1999 Expression and contribution of B7-1 (CD80) and B7-2 (CD86) in the early immune response to Leishmania major infection. Journal of immunology (Baltimore, Md. : 1950) 45 10352289
1997 The role of donor and recipient B7-1 (CD80) in allograft rejection. Journal of immunology (Baltimore, Md. : 1950) 45 9233610
1995 Lipopolysaccharide effectively up-regulates B7-1 (CD80) expression and costimulatory function of human monocytes. Scandinavian journal of immunology 45 8552995
2015 Any value of podocyte B7-1 as a biomarker in human MCD and FSGS? American journal of physiology. Renal physiology 44 26697986
2001 Targeting of a B7-1 (CD80) immunoglobulin G fusion protein to acute myeloid leukemia blasts increases their costimulatory activity for autologous remission T cells. Blood 44 11342441
2001 Building novel binding ligands to B7.1 and B7.2 based on human antibody single variable light chain domains. Journal of molecular biology 44 11439026
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
1998 Cryptococcus neoformans differently regulates B7-1 (CD80) and B7-2 (CD86) expression on human monocytes. European journal of immunology 40 9485191
1998 Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma. Journal of cancer research and clinical oncology 38 9719501
1996 Expression and function of B7-1 and B7-2 in hapten-induced contact sensitivity. European journal of immunology 38 8625983
2020 PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies. Trends in molecular medicine 37 33199209
2002 Perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells. The Journal of experimental medicine 37 11956287
2000 Autoantibody responses and pathology regulated by B7-1 and B7-2 costimulation in MRL/lpr lupus. Journal of immunology (Baltimore, Md. : 1950) 36 10975864
2000 Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse. Gene therapy 36 11175312
1999 B7.2 (CD86) but not B7.1 (CD80) costimulation is required for the induction of low dose oral tolerance. Journal of immunology (Baltimore, Md. : 1950) 33 10438973
1998 Immune stimulatory potential of B7.1 and B7.2 retrovirally transduced melanoma cells: suppression by interleukin 10. British journal of cancer 32 9652756
1997 Anomalous expression of costimulatory molecules B7-1, B7-2 and CD28 in primary biliary cirrhosis. Journal of hepatology 32 9148019
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
2002 B7-1 (CD80) and B7-2 (CD 86) expression in human tubular epithelial cells in vivo and in vitro. Nephron 31 12372936
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
1996 Lack of B7-1/BB1 and B7-2/B70 expression on thyrocytes of patients with Graves' disease. Delivery of costimulatory signals from bystander professional antigen-presenting cells. The Journal of clinical endocrinology and metabolism 30 8923872
2020 Mechanistic dissection of the PD-L1:B7-1 co-inhibitory immune complex. PloS one 29 32497097

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