Affinage

CD86

T-lymphocyte activation antigen CD86 · UniProt P42081

Length
329 aa
Mass
37.7 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD86 (B7-2) is a monomeric IgV-type cell-surface costimulatory ligand on antigen-presenting cells that, together with the related CD80, engages CD28 and CTLA-4 on T cells to deliver the second signal required for productive T cell activation, IL-2 production, and proliferation (PMID:7694363, PMID:7504059, PMID:7519245). Unlike CD80, its mRNA is constitutively expressed and rapidly induced on B cells following BCR engagement, allowing CD28-dependent costimulation independently of CD80 (PMID:7694363, PMID:7504059, PMID:7519638). CD86 binds CD28 and CTLA-4 with avidity comparable to CD80 but with markedly faster dissociation kinetics and through distinct, only partially overlapping binding determinants — it is uniquely sensitive to CTLA-4 MYPPPY-domain substitutions and to the CTLA4Ig Y100A mutation, and its V domain alone suffices for CTLA-4 binding (PMID:7534620, PMID:8557978, PMID:8609386). Structurally CD86 is monomeric in solution and on the cell surface, in contrast to dimeric CD80, a difference that underlies their non-overlapping oligomeric behavior and differential signaling (PMID:12606712, PMID:16221763). Functionally CD80 and CD86 are not redundant: CD86 preferentially costimulates early IL-4 production and Th2-skewed differentiation, and engagement of CD28 by CD86 fails to induce the CD28 tyrosine phosphorylation and PI3K recruitment elicited by CD80 (PMID:7538442, PMID:7534215, PMID:9915850). In vivo, CD86 and CD80 have overlapping CD28-dependent roles, since either ligand alone supports the lymphoproliferative phenotype of CTLA-4-deficient mice while loss of both abolishes it (PMID:9892625). CD86 is selectively targeted by CTLA-4 transendocytosis, but in a fate distinct from CD80: CTLA-4 detaches from CD86 in a pH-dependent manner and recycles to the surface, and clinically relevant autoimmune CTLA-4 mutations selectively disrupt this CD86 transendocytosis (PMID:35999394). Beyond its forward costimulatory ligand role, CD86 transmits reverse signals into B cells through prohibitin-1/2 transmembrane adaptors and its cytoplasmic PKC phosphorylation sites, driving IκBα phosphorylation, NF-κB activation, Oct-2 and XBP-1 induction, and IgG secretion by class-switched B cells (PMID:19933871, PMID:23241883). CD86 expression is tightly controlled: it is repressed on self-reactive B cells through Tet2/Tet3-dependent recruitment of HDAC1/2 to the Cd86 locus to enforce peripheral tolerance, and its failed repression causes autoantibody production and lupus-like disease (PMID:9705947, PMID:32572241). Pathogens manipulate CD86 — Toxoplasma gondii upregulates it on macrophages via a JNK-dependent pathway, KSHV K5 selectively drives its dynamin-dependent endocytosis to impair T cell activation, and bacterial superantigens bridge CD86 and CD28 at their dimer interfaces to potentiate cytokine storm (PMID:21911468, PMID:11413168, PMID:27708164).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Establishing CD86 as a distinct CD28/CTLA-4 counter-receptor answered whether B cells possess a constitutive costimulatory ligand separate from CD80.

    Evidence Molecular cloning with cDNA transfection and functional T cell proliferation/IL-2 assays in human and murine systems

    PMID:7504059 PMID:7694363

    Open questions at the time
    • Did not resolve why constitutive vs inducible expression matters functionally
    • No structural or kinetic distinction from CD80 yet
  2. 1994 High

    Kinetic and mutagenesis analysis showed CD86 binds CD28/CTLA-4 through distinct determinants and with faster dissociation than CD80, establishing that the two ligands are biochemically non-equivalent.

    Evidence Cell-binding assays, CTLA4Ig competition, dissociation kinetics, and Y100A mutant CTLA4Ig binding

    PMID:7534620

    Open questions at the time
    • Functional consequence of faster off-rate not yet defined
    • Binding-site architecture not visualized structurally
  3. 1994 High

    Demonstrating BCR-inducible, CD80-independent CD86 expression and its serological identity to B7-2/B70 unified the antigen nomenclature and located CD86 in B cell activation.

    Evidence Flow cytometry on BCR-transgenic B cells, CD28-blocking functional assays, and antibody (FUN-1/BU-63) blocking with cDNA transfectants

    PMID:7519245 PMID:7519638 PMID:7520767

    Open questions at the time
    • Transcriptional control of inducibility not defined
    • Whether differential regulation alters T cell outcome unaddressed
  4. 1995 High

    Showing CD86 preferentially drives early IL-4 and Th2 differentiation while anti-B7 blockade alters EAE severity established functional divergence of CD80 and CD86 in directing T helper outcomes.

    Evidence B7-transfected CHO costimulation of naive T cells with cytokine readouts, and in vivo EAE antibody blockade with adoptive transfer and IL-4 neutralization

    PMID:7534215 PMID:7538442

    Open questions at the time
    • Molecular basis of the Th2 bias unresolved
    • Whether bias reflects kinetics, oligomeric state, or signaling unknown
  5. 1996 High

    Mapping CTLA-4 substitutions that abolish CD86 but not CD80 binding, and finding the CD86 V domain alone is sufficient, pinpointed distinct overlapping binding sites on CTLA-4.

    Evidence Site-directed CTLA-4 mutagenesis with SPR kinetics and transfectant binding assays

    PMID:8557978 PMID:8609386

    Open questions at the time
    • Co-crystal of the CD86/CTLA-4 interface not yet available
    • Functional consequence of distinct sites unaddressed
  6. 1996 High

    Forced constitutive B7-2 on B cells preventing Fas-mediated deletion of self-reactive B cells established that CD86 repression is required for peripheral B cell tolerance.

    Evidence B7.2 transgenic mice with adoptive transfer, Fas-deficient comparison, and anti-B7.2 blocking

    PMID:9705947

    Open questions at the time
    • Mechanism enforcing CD86 repression unknown
    • Whether forward or reverse CD86 signaling drives the phenotype unclear
  7. 1999 High

    Genetic epistasis and signaling comparison showed CD86 and CD80 have overlapping CD28-dependent functions in vivo yet differ in CD28 phosphorylation/PI3K recruitment, defining redundancy at the phenotypic level and divergence at the biochemical level.

    Evidence B7-1/B7-2 double knockout on CTLA-4-deficient background, plus CD28 phosphorylation, PI3K co-IP, and NFAT assays comparing CD80 vs CD86 transfectants

    PMID:9892625 PMID:9915850

    Open questions at the time
    • How differential CD28 phosphorylation maps to distinct outcomes unresolved
    • Contribution of CD86 reverse signaling not separated
  8. 2003 High

    Crystallography and live-cell FRET established that CD86 is monomeric whereas CD80 is dimeric, providing a structural basis for their differential signaling and the absence of heterodimers.

    Evidence X-ray crystallography of the CD86 IgV domain at 2.7 Å and photobleaching FRET on live cells with dimer-interface mutagenesis

    PMID:12606712 PMID:16221763

    Open questions at the time
    • Direct link from oligomeric state to signaling output not demonstrated
    • Stoichiometry of CD86 in receptor-bound state in situ unclear
  9. 2003 High

    Identifying CD86 as the costimulatory ligand mediating IDO induction in DCs and contact-inhibition by epithelial cells extended CD86 function to CTLA-4-dependent immune suppression.

    Evidence IDO activity assays with B7/CTLA-4 blocking and cross-linking, and IPE-T cell suppression assays using CD80/CD86 and CTLA-4/CD28 knockouts

    PMID:12835481 PMID:15034022

    Open questions at the time
    • Signaling pathway into DCs downstream of CD86 ligation not detailed
    • Relative roles of CD80 vs CD86 in IDO not fully separated
  10. 2004 Medium

    Opposing roles of CD86 and CD80 on DCs in Treg suppression indicated their expression ratio tunes regulatory output.

    Evidence Antibody blocking of CD86 vs CD80 in alloantigen DC-T suppression assays with DC maturation profiling

    PMID:14978077

    Open questions at the time
    • Molecular basis of opposing effects not defined
    • Single-lab functional blocking without genetic confirmation
  11. 2009 High

    Demonstrating that CD86 engagement on class-switched B cells drives IgG secretion and XBP-1 induction established a cell-intrinsic reverse-signaling role independent of T cell help.

    Evidence Mixed bone marrow chimeras lacking B7 only on B cells, in vitro CD86 engagement, IgG ELISA, and XBP-1 RT-PCR

    PMID:19933871

    Open questions at the time
    • Cytoplasmic signaling machinery not yet identified at this stage
    • Physiological ligand engaging CD86 in vivo unclear
  12. 2011 High

    Defining the prohibitin-1/2 / cytoplasmic-domain axis and follicular B cell requirement explained how CD86 reverse signaling activates NF-κB and supports germinal center/TFH biology.

    Evidence Proteomic CD86 pulldown with Phb1/2 shRNA, cytoplasmic domain mutagenesis and phosphorylation assays, plus B7-2 KO infection models with mixed adoptive transfer

    PMID:21441451 PMID:23241883

    Open questions at the time
    • How prohibitins couple to PLCγ2/PKC mechanistically unresolved
    • Whether the same axis operates outside B cells unknown
  13. 2011 High

    Showing pathogen-driven and viral manipulation of CD86 surface levels (Toxoplasma JNK-dependent upregulation; KSHV K5 dynamin-dependent endocytosis) revealed CD86 as a contested node in host-pathogen conflict.

    Evidence Macrophage/monocyte infection with MAPK inhibitor panel and T cell blocking assays; K5/K3 transfection with dominant-negative dynamin rescue and T cell activation assays

    PMID:11413168 PMID:21911468

    Open questions at the time
    • Transcription factors downstream of JNK at the Cd86 locus not identified
    • K5 substrate-recognition determinants on CD86 unmapped
  14. 2020 High

    Linking Tet2/Tet3 demethylases to HDAC1/2 recruitment at the Cd86 locus defined the epigenetic mechanism repressing CD86 on self-reactive B cells and its causal role in lupus-like autoimmunity.

    Evidence Conditional Tet2/Tet3 B cell knockout, HDAC1/2 ChIP at Cd86, anti-CD86 blockade, and autoantibody measurement

    PMID:32572241

    Open questions at the time
    • How Tet enzymes direct HDAC recruitment to Cd86 mechanistically unclear
    • Anti-CD86 only partially rescued disease, leaving CD86-independent contributions
  15. 2022 High

    Resolving the distinct CTLA-4 transendocytosis fate of CD86 (pH-dependent CTLA-4 recycling vs CD80-driven degradation) and tying it to autoimmune CTLA-4 mutations explained ligand-specific control of CTLA-4 turnover.

    Evidence Transendocytosis assays, pH-dependent dissociation, ubiquitylation/endosomal trafficking analysis, and clinical CTLA-4 mutation analysis

    PMID:35999394

    Open questions at the time
    • Structural basis of pH-dependent CD86/CTLA-4 detachment not solved
    • In vivo quantitative impact on T cell tolerance unclear
  16. 2016 High

    Showing that superantigens engage CD86 at its dimer interface to bridge CD28 identified CD86 as a direct target for toxin-driven cytokine storm and a therapeutic interception point.

    Evidence Direct binding of superantigens to surface B7-2 and CD28, peptide competition, cytokine assays, and lethal in vivo challenge with mimetic peptides

    PMID:27708164

    Open questions at the time
    • Co-structure of the superantigen/CD86/CD28 ternary complex absent
    • Generality across superantigen families not fully tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD86's monomeric structure, fast binding kinetics, distinct CTLA-4 transendocytosis fate, and prohibitin-dependent reverse signaling are integrated to produce its non-redundant immunological outcomes remains unresolved.
  • No unified model linking oligomeric state, kinetics, and signaling output
  • Receptors mediating CD86's CD28/CTLA-4-independent roles (e.g. on NK cells) unidentified
  • Structural basis of forward vs reverse signaling not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 2
Partners
CD28CTLA4PHB1PHB2

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CD86 (B7-2) was cloned as a counter-receptor for CD28 and CTLA-4; it costimulates IL-2 production and T cell proliferation, and unlike B7-1, its mRNA is constitutively expressed in unstimulated B cells. Molecular cloning, cDNA transfection, functional T cell proliferation assay, IL-2 secretion assay Science High 7504059 7694363
1994 Human CD86 binds CD28 and CTLA-4 with similar overall avidity to CD80 but with distinct kinetics: CD86-CTLA-4 complexes dissociate 5- to 8-fold faster than CD80-CTLA-4 complexes, and CD86 is unable to bind the CTLA4Ig Y100A mutant (>200-fold less than CD80), demonstrating that CD80 and CD86 use different binding determinants on CTLA-4. Cell-binding assays, CTLA4Ig competition, dissociation kinetics measurement, mutant CTLA4Ig binding experiments Immunity High 7534620
1994 CD86 expression is rapidly induced on the surface of B cells after BCR (Ig receptor) engagement, whereas B7-1 is not upregulated under the same conditions; BCR-induced CD86 costimulates T cell proliferation in a CD28-dependent manner independent of B7-1. Flow cytometry on normal and BCR-transgenic B cells, functional CD28-blocking experiments, anti-IgM or antigen stimulation Journal of Immunology High 7519638
1994 The serologically defined CD86 differentiation antigen (recognized by mAbs FUN-1 and BU-63) is identical to B7-2/B70; FUN-1 completely blocks the costimulatory activity of B7-2 in functional assays. cDNA transfection into cells, antibody binding, functional costimulation block assay Blood High 7520767
1994 B7-1 and B7-2 can be independently regulated by the same stimulus on B cells (LPS or anti-IgD-dextran): B7-2 expression is significantly higher than B7-1 at all time points assayed, and blocking B7-2 inhibits TCR-dependent T cell proliferation and cytokine production without affecting early TCR signaling (CD69 or IL-2Rα induction). Flow cytometry, antibody blocking in T cell proliferation and cytokine assays, B cell stimulation experiments Journal of Experimental Medicine High 7519245
1995 B7-2 (CD86), but not B7-1, preferentially costimulates the initial production of IL-4, particularly in naive T cells; repetitive costimulation with B7-2 results in moderate IL-4 and IL-2, whereas B7-1 drives high IL-2 and low IL-4, demonstrating that the two ligands direct distinct Th differentiation outcomes. In vitro T cell stimulation with B7-transfected CHO cells, cytokine ELISA/bioassay, CD45RA+ naive T cell differentiation assays Immunity High 7538442
1995 Anti-B7-1 treatment skews toward Th2 (generating IL-4-producing T cells that can transfer protection from EAE), whereas anti-B7-2 treatment increases EAE severity; these effects require initial cytokine secretion since co-treatment with anti-IL-4 prevents disease amelioration by anti-B7-1. In vivo antibody blockade in EAE model, adoptive transfer of T cell clones, cytokine neutralization Cell High 7534215
1996 Constitutive B7.2 transgene expression on B cells is sufficient to prevent Fas-mediated deletion of self-reactive B cells and trigger extensive T cell-dependent clonal expansion and autoantibody secretion, demonstrating that repression of B7.2 is critical for Fas-mediated peripheral B cell tolerance. B7.2 transgenic mice, adoptive transfer, Fas-deficient comparison, anti-B7.2 blocking, T cell-dependent B cell expansion assay Journal of Experimental Medicine High 9705947
1999 Either B7-1 or B7-2 alone (without both) is sufficient to produce the lymphoproliferative phenotype in CTLA-4-deficient mice; eliminating both B7-1 and B7-2 completely abrogates lymphoproliferation, demonstrating overlapping and CD28-dependent functions of the two ligands in vivo. Genetic epistasis — B7-1/B7-2 double knockout bred onto CTLA-4-deficient background, lymphocyte activation and organ infiltration assessment Journal of Experimental Medicine High 9892625
2003 The crystal structure of the receptor-binding (IgV-type) domain of human B7-2 at 2.7 Å resolution reveals that unliganded B7-2 is monomeric in solution and in crystalline form, whereas B7-1 dimerizes through hydrophobic contacts; the B7-2 dimer observed in the B7-2/CTLA-4 complex has a hydrophilic interface, providing a structural basis for preventing B7-1/B7-2 heterodimers and for differential signaling. X-ray crystallography at 2.7 Å resolution, solution state analysis Proceedings of the National Academy of Sciences of the United States of America High 12606712
2005 Using photobleaching-based FRET, B7-2 exists as a monomer on the cell surface whereas B7-1 exists predominantly as dimers; mutations in B7-1 dimer interface convert it to a monomeric surface state, validating the crystallographic dimer interface and showing that B7-1 and B7-2 do not form hetero-oligomers. Photobleaching-based FRET (pbFRET) on live cells, site-directed mutagenesis of B7-1 dimer interface Proceedings of the National Academy of Sciences of the United States of America High 16221763
1996 Five single amino acid substitutions within the MYPPPY domain of CTLA-4 modestly affect CD80 binding but each completely abrogates CD86 binding, demonstrating that CD80 and CD86 bind with different kinetics and utilize distinct but overlapping sites on CTLA-4; additionally, the V domain of CD86 (but not CD80) alone is sufficient for CTLA-4 binding. Site-directed mutagenesis of CTLA-4, surface plasmon resonance (SPR) kinetics, transfectant binding assays Journal of Immunology High 8557978 8609386
1999 CD80 engagement of CD28 (and anti-CD28 mAb) induces robust tyrosine phosphorylation of CD28 itself and enhanced PI3K association with CD28, whereas CD86 engagement fails to induce detectable CD28 tyrosyl phosphorylation or PI3K association under the same conditions; both ligands equivalently phosphorylate CBL and VAV and activate NFAT. Tyrosine phosphorylation assays of CD28, PI3K co-immunoprecipitation with CD28, NFAT reporter assay, cytokine ELISA in Jurkat and primary human T cells stimulated with CHO-CD80 vs CHO-CD86 transfectants Journal of Biological Chemistry High 9915850
2004 Ligation of B7-1/B7-2 on dendritic cells by CTLA-4/CD28 expressed on T cells is obligately required to trigger functional IDO (indoleamine 2,3-dioxygenase) activity; disrupting this interaction leaves IDO inactive, and direct antibody-mediated cross-linking of B7-1/B7-2 fully restores IDO activity; only CD4+ T cells trigger IDO activation. IDO activity assay on human monocyte-derived DCs, antibody blocking of B7-1/B7-2 or CTLA-4/CD28, direct Ab cross-linking of B7 molecules, CD4/CD8 T cell subset experiments Journal of Immunology High 15034022
2004 CD86 and CD80 have opposing functions on dendritic cells in regulating Treg suppression: blocking CD86 potently enhances Treg suppression, whereas blocking CD80 impairs Treg suppression; CD80 and CD86 expression ratio on DCs changes during maturation and correlates with Treg suppressive capacity. Antibody blocking of CD86 and CD80 in alloantigen DC-T cell suppression assays, flow cytometry of DC maturation states Journal of Immunology Medium 14978077
2001 The KSHV viral protein K5 (but not K3) selectively enhances endocytosis of ICAM-1 and B7-2 from the surface of B cells, without affecting B7-1; this K5-induced downregulation is reversed by a dominant-negative dynamin mutant, demonstrating enhanced endocytosis as the mechanism; K5-transfected B cells show substantially impaired ability to induce T cell activation. K5/K3 cDNA transfection in BJAB cells, flow cytometry of surface markers, dominant-negative dynamin co-expression rescue, T cell activation assay Journal of Clinical Investigation High 11413168
2003 Iris pigment epithelial (IPE) cells constitutively express CD86 on their surface, and this CD86 enables them to contact-inhibit T cells by directly engaging CTLA-4 on T cells; blocking CD86 (anti-CD86 or CD86/CD80 KO IPE) or CTLA-4 (CTLA4Ig or CTLA-4 KO T cells) abrogates IPE-mediated T cell suppression, whereas CD28 KO T cells are still suppressed. Flow cytometry of IPE surface markers, antibody blocking, CD80/CD86 double KO and CTLA-4/CD28 KO mice, in vitro T cell suppression assay Journal of Experimental Medicine High 12835481
2009 Direct engagement of B7-2 (CD86) on B cells promotes IgG secretion by already class-switched B cells in a B7-1/2-on-B-cell-specific manner; B7-2 engagement induces expression of XBP-1 and spliced XBP1 (indicating increased protein synthesis) and this effect is independent of effects on T cell activation or germinal center formation. Mixed bone marrow irradiation chimeras lacking B7-1/2 only on B cells, in vitro B7-2 engagement of class-switched B cells, ELISA for IgG/IgM, XBP-1 expression analysis by RT-PCR Journal of Immunology High 19933871
2012 Prohibitin (Phb)1 and Phb2 bind to CD86 via tyrosine-containing transmembrane adaptor interactions; CD40 priming increases Phb1/2 expression and their association with CD86. Both Phb1/2 and the CD86 cytoplasmic domain (including serine/threonine PKC phosphorylation sites) are required for CD86-induced IκBα phosphorylation and NF-κB activation leading to Oct-2 and IgG1 upregulation; only Phb1/2 (not cytoplasmic domain) are required for CD86-induced PLCγ2 and PKCα/βII phosphorylation. Proteomics-based pulldown/co-IP of CD86-interacting proteins, shRNA knockdown of Phb1/2, CD86 cytoplasmic domain truncation and site-directed mutagenesis, phosphorylation assays, IgG1 ELISA and mRNA quantification Journal of Immunology High 23241883
2011 Toxoplasma gondii upregulates B7-2 (but not B7-1) on macrophages through a JNK (Jun N-terminal kinase)-dependent but MyD88/TRIF-independent mechanism; parasite invasion is required; this induction occurs at the transcript level; T. gondii-infected macrophages stimulate naive T cell proliferation in a B7-2-dependent manner; the same JNK-dependent mechanism operates in human monocytes. Infection of bone marrow-derived macrophages and human monocytes, MAPK inhibitor panel (JNK, ERK, p38), RT-PCR, flow cytometry, T cell proliferation blocking assays, genome-wide transcriptional analysis Infection and Immunity High 21911468
2020 Tet2 and Tet3 DNA demethylases in B cells are required for downregulation of CD86 following chronic self-antigen exposure; in Tet2/Tet3-deficient B cells, CD86 fails to be repressed because HDAC1 and HDAC2 accumulate less at the Cd86 locus; anti-CD86 blockade restricts (though does not completely prevent) the aberrant T and B cell activation and lupus-like disease caused by Tet2/Tet3 deficiency. Conditional Tet2/Tet3 double-knockout in B cells, ChIP for HDAC1/HDAC2 at Cd86 locus, anti-CD86 antibody blockade, flow cytometry, autoantibody measurement Nature Immunology High 32572241
2022 CTLA-4 targets both CD80 and CD86 for destruction via transendocytosis, but CD86 results in a distinct fate: in the presence of CD86, CTLA-4 detaches in a pH-dependent manner and recycles back to the cell surface to permit further transendocytosis rounds, whereas CD80 keeps CTLA-4 ligand-bound leading to ubiquitylation and lysosomal degradation; clinically relevant autoimmune disease mutations selectively disrupt CD86 transendocytosis by affecting either CTLA-4 recycling or CD86 binding. Transendocytosis assays, pH-dependent dissociation experiments, ubiquitylation and endosomal trafficking analysis, analysis of clinical CTLA-4 mutations Nature Immunology High 35999394
2016 Bacterial superantigens bind directly to B7-2 (CD86) at its homodimer interface using the same 12-aa β-strand-hinge-α-helix domain they use to bind CD28, thereby bridging and potentiating the B7-2/CD28 interaction; B7-2 dimer interface mimetic peptides competitively block superantigen binding to B7-2 and CD28, attenuate cytokine overexpression, and protect mice from lethal superantigen challenge. Direct binding assays of superantigens to cell-surface B7-2 and CD28, peptide competition assays, cytokine production assays, in vivo lethal challenge model Proceedings of the National Academy of Sciences of the United States of America High 27708164
2002 BCR stimulation and β2-adrenergic receptor (β2AR) stimulation cooperate to regulate B7-2 (CD86) expression on B cells; β2AR stimulation enhances BCR-induced CD86 by increasing B7-2 mRNA stability, NF-κB nuclear binding, and NF-κB-dependent transcription through PKA-, PKC-, and MAPK-dependent mechanisms. In vitro B cell stimulation with BCR and β2AR agonists, mRNA stability assay, NF-κB EMSA and reporter assay, kinase inhibitor panel Journal of Immunology Medium 12055247
2011 B7-2 (but not B7-1) expression specifically on follicular B cells is required for maintenance of the follicular T helper (TFH) cell phenotype and germinal center B cell development; bidirectional interactions between CD28 on activated T cells and B7-2 on follicular B cells are essential, as shown by mixed adoptive transfer experiments. B7-2 KO and B7-1 KO mouse infection model (vaccinia virus), mixed adoptive transfer of B7-2-deficient B cells, flow cytometry of TFH and GC B cells, neutralizing antibody titers Journal of Immunology High 21441451
2012 Induced regulatory T cells (iTregs) acquire both CD80 and CD86 from mature dendritic cells via trogocytosis; CD86 is acquired to a higher extent than CD80; iTregs that acquired CD86 show higher activation markers and enhanced suppressive function compared to those that did not; this trogocytosis occurs independently of CTLA-4, CD28, and PD-L1. Flow cytometry and confocal fluorescence microscopy of iTreg-DC co-cultures, DKO (CD80/CD86 double KO) iTregs used as recipients, suppression assays Cellular & Molecular Immunology Medium 22307040
2017 CD86 (B7.2) functions as a co-receptor for lymphotropic hepatitis C virus (HCV) B-cell infection; cDNA library screening identified CD86 as specific to the lymphotropic HCV strain; silencing CD86 reduces B-cell infection; HCV infection via CD86 inhibits memory B-cell recall responses. cDNA library screening, infectious clone/chimeric virus system, CD86 silencing/knockdown, B cell infection assays, memory B cell recall function assay Nature Communications Medium 28067225
1997 CD28 surface levels are differentially downregulated by B7-1 and B7-2: B7-1 engagement is considerably more effective at downregulating CD28 than B7-2 engagement, indicating a differential functional effect on activated T cells. Flow cytometry of CD28 surface expression on T cells after stimulation with B7-1 or B7-2 transfectants Transplantation Low 9392322
1995 CD86 expressed on vascular endothelial cells costimulates allogeneic CD4+ T cells; blocking anti-CD86 mAb inhibits this proliferative response and induces alloantigen-specific T cell anergy, whereas CD80 is undetectable on endothelial cells even after IFN-γ treatment. Flow cytometry of HUVEC and MVEC, antibody blocking of allogeneic MLR, CD28-dependent anergy induction International Immunology Medium 7495740
1999 Human CD80 and CD86 expressed on murine B16 melanoma cells trigger NK cell-mediated cytotoxicity; this triggering is independent of CD28 and CTLA-4 (not detected on the NK cell lines tested), suggesting NK cells use distinct receptors to interact with CD80/CD86. Transfection of CD80/CD86 into B16 melanoma, NK cell cytotoxicity assay, antibody blocking, flow cytometry for CD28/CTLA-4 on NK cells Journal of Immunology Medium 10510357
2013 CD86 expressed on activated NK cells serves as an activating receptor: CTLA4Ig ligation of CD86 on NK cells increases expression of CD107a and perforin and enhances NK cell killing of tumor targets; blocking CD86 on a CD86-high human NK cell line inhibits the CTLA4Ig-enhanced killing. NK depletion experiments in vivo, flow cytometry for CD86 on activated NK cells, CD107a/perforin upregulation assay, NK cytotoxicity assay with anti-CD86 blocking PloS One Medium 24349559
2021 Pomalidomide (Pom) reverses KSHV-induced downregulation of B7-2 on primary effusion lymphoma (PEL) cells through a cereblon-dependent mechanism involving PI3K signaling; restoration of B7-2 on PEL cells leads to increased T cell activation and NK-mediated cytotoxicity; Pom-resistant cells with ~90% reduction in cereblon no longer upregulate B7-2, and cereblon-knockout cells behave similarly. Pom treatment of PEL cells, cereblon KO and Pom-resistant cell line generation, surface B7-2 flow cytometry, T cell activation and NK cytotoxicity assays, PI3K inhibitor experiments PLoS Pathogens Medium 33411730

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
1993 Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science (New York, N.Y.) 888 7694363
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
1995 Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. The Journal of experimental medicine 539 7532678
1995 B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity 504 7538442
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
1995 Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. Journal of immunology (Baltimore, Md. : 1950) 379 7541819
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
1993 Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production. The Journal of experimental medicine 363 7504059
1999 B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by TNFalpha. Immunity 357 10549624
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
1996 Costimulatory function and expression of CD40 ligand, CD80, and CD86 in vascularized murine cardiac allograft rejection. Proceedings of the National Academy of Sciences of the United States of America 334 8943044
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
2004 CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells. Journal of immunology (Baltimore, Md. : 1950) 224 14978077
2003 What's the difference between CD80 and CD86? Trends in immunology 221 12810107
2001 A viral protein that selectively downregulates ICAM-1 and B7-2 and modulates T cell costimulation. The Journal of clinical investigation 194 11413168
2022 Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation. Nature immunology 178 35999394
1999 CD28/CTLA-4 and CD80/CD86 families: signaling and function. Immunologic research 142 10374692
2001 Histamine induces CD86 expression and chemokine production by human immature dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 123 11342615
1996 B7-2 (CD86) is essential for the development of IL-4-producing T cells. International immunology 120 8921434
1996 Differential expression and function of CD80 (B7-1) and CD86 (B7-2) on human peripheral blood monocytes. Immunology 111 9014827
1999 B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). The Journal of experimental medicine 108 9892625
2019 Local Delivery of Ox40l, Cd80, and Cd86 mRNA Kindles Global Anticancer Immunity. Cancer research 96 30692215
2001 Defective expression of B7-2 (CD86) on monocytes of dialysis patients correlates to the uremia-associated immune defect. Kidney international 95 11260399
2005 B7-1 and B7-2: similar costimulatory ligands with different biochemical, oligomeric and signaling properties. Immunology letters 94 16413062
2021 CD86+ Antigen-Presenting B Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T-cell Responses. Cancer immunology research 88 34155067
2020 Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis. Genome medicine 88 32580776
2009 B7-1/2 (CD80/CD86) direct signaling to B cells enhances IgG secretion. Journal of immunology (Baltimore, Md. : 1950) 87 19933871
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
2003 Iris pigment epithelium expressing CD86 (B7-2) directly suppresses T cell activation in vitro via binding to cytotoxic T lymphocyte-associated antigen 4. The Journal of experimental medicine 83 12835481
1994 The B7-2 (B70) costimulatory molecule expressed by monocytes and activated B lymphocytes is the CD86 differentiation antigen. Blood 83 7520767
1997 Expression of costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on human hepatocellular carcinoma. Hepatology (Baltimore, Md.) 82 9141426
1999 NK cell triggering by the human costimulatory molecules CD80 and CD86. Journal of immunology (Baltimore, Md. : 1950) 79 10510357
1999 Anti-CD86 (B7.2) treatment abolishes allergic airway hyperresponsiveness in mice. American journal of respiratory and critical care medicine 78 10228138
2020 Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity. Nature immunology 76 32572241
1996 Costimulation of IL-4 production by murine B7-1 and B7-2 molecules. Journal of immunology (Baltimore, Md. : 1950) 75 8609397
2012 Trogocytosis of CD80 and CD86 by induced regulatory T cells. Cellular & molecular immunology 72 22307040
1998 Repression of B7.2 on self-reactive B cells is essential to prevent proliferation and allow Fas-mediated deletion by CD4(+) T cells. The Journal of experimental medicine 72 9705947
2003 Crystal structure of the receptor-binding domain of human B7-2: insights into organization and signaling. Proceedings of the National Academy of Sciences of the United States of America 69 12606712
2011 B cell-specific expression of B7-2 is required for follicular Th cell function in response to vaccinia virus. Journal of immunology (Baltimore, Md. : 1950) 65 21441451
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
2005 Relationship of CD86 surface marker expression and cytotoxicity on dendritic cells exposed to chemical allergen. Toxicology and applied pharmacology 63 15885735
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
2001 CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases. The American journal of gastroenterology 60 11693331
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
1999 CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28. The Journal of biological chemistry 57 9915850
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
2016 CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice. Experimental and therapeutic medicine 53 26998006
2013 Circulating CD40+ and CD86+ B cell subsets demonstrate opposing associations with risk of stroke. Arteriosclerosis, thrombosis, and vascular biology 53 24202305
1996 Interactions of CD80 and CD86 with CD28 and CTLA4. Journal of immunology (Baltimore, Md. : 1950) 53 8609386
2002 B cell receptor- and beta 2-adrenergic receptor-induced regulation of B7-2 (CD86) expression in B cells. Journal of immunology (Baltimore, Md. : 1950) 51 12055247
2016 Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2/CD28 costimulatory receptor interaction. Proceedings of the National Academy of Sciences of the United States of America 48 27708164
1999 CD86 (B7-2) can function to drive MHC-restricted antigen-specific CTL responses in vivo. Journal of immunology (Baltimore, Md. : 1950) 47 10092797
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
1997 B7-2 requirement for helminth-induced granuloma formation and CD4 type 2 T helper cell cytokine expression. Journal of immunology (Baltimore, Md. : 1950) 46 9190944
2010 Polymorphisms affecting micro-RNA regulation and associated with the risk of dietary-related cancers: a review from the literature and new evidence for a functional role of rs17281995 (CD86) and rs1051690 (INSR), previously associated with colorectal cancer. Mutation research 45 20971123
2003 Monocyte-derived IL12, CD86 (B7-2) and CD40L expression in relapsing and progressive multiple sclerosis. Clinical immunology (Orlando, Fla.) 45 12672403
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
1995 CD86 (B70/B7-2) on endothelial cells co-stimulates allogeneic CD4+ T cells. International immunology 43 7495740
1997 Regulation of self-tolerance by CD80/CD86 interactions. Current opinion in immunology 42 9492990
1995 Glycosylphosphatidylinositol-modified murine B7-1 and B7-2 retain costimulator function. Journal of immunology (Baltimore, Md. : 1950) 42 7499830
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
1997 B7-2 blockade enhances T cell responses to Leishmania donovani. Journal of immunology (Baltimore, Md. : 1950) 40 9379045
2018 CD86 Expression by Monocytes Influences an Immunomodulatory Profile in Asymptomatic Patients with Chronic Chagas Disease. Frontiers in immunology 39 29599775
2012 Prohibitins and the cytoplasmic domain of CD86 cooperate to mediate CD86 signaling in B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 38 23241883
2000 Bacterial pathogens induce abscess formation by CD4(+) T-cell activation via the CD28-B7-2 costimulatory pathway. Infection and immunity 38 11083777
1998 Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma. Journal of cancer research and clinical oncology 38 9719501
1997 Characterization of rat CD80 and CD86 by molecular cloning and mAb. International immunology 38 9237108
1996 Expression and function of B7-1 and B7-2 in hapten-induced contact sensitivity. European journal of immunology 38 8625983
1995 Role of B70/B7-2 in CD4+ T-cell immune responses induced by dendritic cells. Immunology 38 7558137
2017 Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nature communications 37 28067225
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
1997 Functional CD86 (B7-2/B70) is predominantly expressed on Langerhans cells in atopic dermatitis. The British journal of dermatology 37 9217814
2014 Small interfering RNA against CD86 during allergen challenge blocks experimental allergic asthma. Respiratory research 36 25344652
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
2013 CD86 is an activation receptor for NK cell cytotoxicity against tumor cells. PloS one 35 24349559
2011 Toxoplasma gondii induces B7-2 expression through activation of JNK signal transduction. Infection and immunity 35 21911468
2001 IL-3 induces B7.2 (CD86) expression and costimulatory activity in human eosinophils. Journal of immunology (Baltimore, Md. : 1950) 35 11714768
2005 CD80 and CD86 costimulatory molecules regulate crescentic glomerulonephritis by different mechanisms. Kidney international 34 16014035
1996 Functional CD86 (B7-2/B70) on cultured human Langerhans cells. The Journal of investigative dermatology 34 8592066
2004 Clinical significance of costimulatory molecules CD80/CD86 expression in IgA nephropathy. Kidney international 33 14871408
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
1997 T cell-mediated elimination of B7.2 transgenic B cells. Immunity 33 9075933
1996 Expression and function of CD80 and CD86 costimulator molecules on synovial dendritic cells in chronic arthritis. Arthritis and rheumatism 33 8702435
2001 Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver. Hepatology (Baltimore, Md.) 32 11584372
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
2002 B7-1 (CD80) and B7-2 (CD 86) expression in human tubular epithelial cells in vivo and in vitro. Nephron 31 12372936
2021 Pomalidomide restores immune recognition of primary effusion lymphoma through upregulation of ICAM-1 and B7-2. PLoS pathogens 30 33411730
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
1998 Expression and co-stimulatory function of B7-2 on murine CD4+ T cells. European journal of immunology 30 9541581
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
2003 Dual expression of CD80 and CD86 produces a tumor vaccine superior to single expression of either molecule. Cellular immunology 29 12798304
1997 Differential down-regulation of CD28 by B7-1 and B7-2 engagement. Transplantation 29 9392322
2005 CD86 and beta2-adrenergic receptor stimulation regulate B-cell activity cooperatively. Trends in immunology 28 15797507

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