CD86 (B7-2) is a type I transmembrane glycoprotein of the immunoglobulin superfamily (IgV and IgC ectodomains, short cytoplasmic tail) expressed on antigen-presenting cells, including B cells, monocytes and dendritic cells, where it is constitutive at low level and rapidly upregulated on activation. Its ectodomain is a ligand for two T cell receptors: CD28, which delivers the antigen-independent costimulatory 'second signal' that, together with TCR engagement, drives naive T cell proliferation, IL-2 production and effector differentiation; and CTLA4, a higher-affinity inhibitory receptor that competes CD86 away from CD28 and can strip it from APCs. Compared with CD80, CD86 is monomeric, binds both receptors with lower affinity and with less bias toward CTLA4, and is expressed earlier, making it a key early costimulatory ligand. Surface levels are regulated by MARCH-family E3 ligase (MARCH1 in APCs, also MARCH8) ubiquitination and lysosomal degradation, and CD86 is also found on APC-derived exosomes. Studies in mouse suggest CD86 engagement can also signal back into B cells to modulate IgG1 production and NF-kB activity. It is the target of the CTLA4-Ig therapeutics abatacept and belatacept.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002639 positive regulation of immunoglobulin production | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from mouse Cd86 (P42082): CD86 engagement on B cells regulates IgG1 production. Reason: Based on mouse studies of CD86 'reverse' signalling in B cells (UniProt, By similarity). Plausible and consistent with CD86 expression on activated B cells, but this is a secondary B-cell-intrinsic role; the core function of CD86 is as the APC ligand for CD28/CTLA4. No direct human evidence was found in the cached literature. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Also involved in the regulation of B cells function, plays a role in regulating the level of IgG(1) produced. |
| GO:0005515 protein binding | IPI PMID:11279501 Structural basis for co-stimulation by the human CTLA-4/B7-2... | MODIFY | Summary: IPI binding of CD86 to CTLA4 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:11279501. Reason: The interaction with CTLA4 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:11279501 the 3.2-A resolution structure of the complex between the disulphide-linked homodimer of human CTLA-4 and the receptor-binding domain of human B7-2 PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:21982860 A secreted protein microarray platform for extracellular pro... | MODIFY | Summary: IPI binding of CD86 to CTLA4 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:21982860. Reason: The interaction with CTLA4 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:25241761 Using an in situ proximity ligation assay to systematically ... | MODIFY | Summary: IPI binding of CD86 to CTLA4 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:25241761. Reason: The interaction with CTLA4 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | MODIFY | Summary: IPI binding of CD86 to CD28 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:32822567. Reason: The interaction with CD28 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:32822567 A Human IgSF Cell-Surface Interactome Reveals a Complex Netw... | MODIFY | Summary: IPI binding of CD86 to CTLA4 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:32822567. Reason: The interaction with CTLA4 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: IPI binding of CD86 to CD28 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:35922511. Reason: The interaction with CD28 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | MODIFY | Summary: IPI binding of CD86 to CTLA4 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:35922511. Reason: The interaction with CTLA4 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005515 protein binding | IPI PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | MODIFY | Summary: IPI binding of CD86 to CD28 (the CD28/CTLA4 receptors for B7 ligands) reported in PMID:9915850. Reason: The interaction with CD28 is real and is the essence of CD86 function, but generic 'protein binding' is uninformative. The partner is a signaling receptor for which CD86 is the established ligand, so the binding is better captured as signaling receptor binding (GO:0005102); the functional consequence is captured separately by receptor ligand activity (GO:0048018), which CD86 already carries by IDA/IBA. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:9915850 Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. PMID:7513726 ETC-1 also bound to both CD28-Ig and CTLA4-Ig fusion proteins. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0005886 plasma membrane | IC PMID:10606960 Expression of costimulatory molecules CD80 and CD86 and thei... | ACCEPT | Summary: IC: CD86 surface expression on tumour-infiltrating T cells and APCs (flow cytometry), inferring plasma membrane. Reason: CD86 is a single-pass type I membrane protein detected on the cell surface by FACS; plasma membrane is correct and core to its function as a cell-surface ligand. Supporting Evidence: PMID:10606960 Costimulation of T lymphocytes by the leucocyte surface molecules CD80 and CD86 expressed on antigen-presenting cells (APC) is required for the development of T cell responses. file:human/CD86/CD86-uniprot.txt Cell membrane |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: IDA (HPA immunofluorescence): CD86 localises to the plasma membrane. Reason: CD86 is a type I transmembrane IgSF protein displayed on the surface of antigen-presenting cells, where it engages CD28/CTLA4 on T cells in trans. Plasma membrane is the correct core location. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. file:human/CD86/CD86-uniprot.txt Single-pass type I membrane protein |
| GO:0005886 plasma membrane | IDA PMID:7694363 Cloning of B7-2: a CTLA-4 counter-receptor that costimulates... | ACCEPT | Summary: IDA: CD86 localises to the plasma membrane. Reason: CD86 is a type I transmembrane IgSF protein displayed on the surface of antigen-presenting cells, where it engages CD28/CTLA4 on T cells in trans. Plasma membrane is the correct core location. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. file:human/CD86/CD86-uniprot.txt Single-pass type I membrane protein |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: IEA (UniProt subcellular location mapping): CD86 localises to the plasma membrane. Reason: CD86 is a type I transmembrane IgSF protein displayed on the surface of antigen-presenting cells, where it engages CD28/CTLA4 on T cells in trans. Plasma membrane is the correct core location. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. file:human/CD86/CD86-uniprot.txt Single-pass type I membrane protein |
| GO:0005886 plasma membrane | NAS PMID:7513726 Molecular cloning and expression of early T cell costimulato... | ACCEPT | Summary: NAS: CD86 localises to the plasma membrane. Reason: CD86 is a type I transmembrane IgSF protein displayed on the surface of antigen-presenting cells, where it engages CD28/CTLA4 on T cells in trans. Plasma membrane is the correct core location. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. file:human/CD86/CD86-uniprot.txt Single-pass type I membrane protein |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2316434 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-2316434): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2400009 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-2400009): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388808 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388808): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388809 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388809): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388814 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388814): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388829 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388829): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388831 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388831): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388832 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388832): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-388833 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-388833): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389158 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389158): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389348 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389348): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389350 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389350): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389352 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389352): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389354 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389354): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-389381 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-389381): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8937656 | ACCEPT | Summary: TAS from Reactome (Reactome:R-HSA-8937656): B7-2 participates as a plasma membrane component of the CD28 costimulation/CTLA4 events. Reason: Reactome places CD86 (B7-2) at the APC plasma membrane in its CD28 co-stimulation reactions; consistent with experimental localisation. Accepted as plasma membrane location. Supporting Evidence: Reactome:R-HSA-388808 CD28 delivers the costimulatory signal by interacting with its ligand B7-2 on the antigen-presenting cell file:human/CD86/CD86-uniprot.txt Expressed on the surfaces of antigen-presenting cells. |
| GO:0006955 immune response | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: immune response, inherited across the B7/CD28-ligand family. Reason: CD86 is a central costimulatory ligand in adaptive immune responses; the broad IBA term is correct, though the more informative process is T cell costimulation. Supporting Evidence: PMID:7694363 additional molecules expressed on antigen-presenting cells deliver essential costimulatory signals |
| GO:0006955 immune response | TAS PMID:7694363 Cloning of B7-2: a CTLA-4 counter-receptor that costimulates... | ACCEPT | Summary: TAS: B7-2 costimulatory signal needed for T cell immune responses. Reason: Correct but broad; consistent with the IBA. T cell costimulation is the specific process. Supporting Evidence: PMID:7694363 It is likely that B7-2 provides a critical early costimulatory signal determining if the T cell will contribute to an immune response or become anergic. |
| GO:0007165 signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: signal transduction. Reason: CD86 initiates signalling as the ligand of CD28 (in the T cell), and possibly via reverse signalling in B cells (mouse). The generic term is not wrong but adds little beyond receptor ligand activity and T cell costimulation. Supporting Evidence: PMID:9915850 ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA: positive regulation of cell population proliferation. Reason: The proliferation CD86 promotes is specifically T cell proliferation (costimulation with TCR signal). Replace with positive regulation of T cell proliferation (GO:0042102). Proposed replacements: positive regulation of T cell proliferation Supporting Evidence: PMID:7694363 B7-2 also costimulates IL-2 production and T cell proliferation. |
| GO:0008284 positive regulation of cell population proliferation | TAS PMID:7513726 Molecular cloning and expression of early T cell costimulato... | MODIFY | Summary: TAS: B7-2/ETC-1 enhances CD4 T cell proliferation. Reason: The cited paper shows enhancement of CD4 T cell proliferation specifically; the cell type should be specified using positive regulation of T cell proliferation (GO:0042102). Proposed replacements: positive regulation of T cell proliferation Supporting Evidence: PMID:7513726 ETC-1 showed profound T cell costimulatory activity as demonstrated by its ability to enhance CD4 T cell proliferation in response to Con A or anti-CD3 stimulation |
| GO:0009897 external side of plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: external side of plasma membrane. Reason: The IgV/IgC ectodomain that binds CD28/CTLA4 is displayed on the external face of the APC plasma membrane. Accepted as the most precise location term. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Single-pass type I membrane protein PMID:11279501 Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a stimulatory signal for T-cell activation |
| GO:0009967 positive regulation of signal transduction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA IEA: positive regulation of signal transduction. Reason: Broadly true (CD86 augments TCR signalling via CD28), but it is captured more specifically by positive regulation of T cell receptor signaling pathway (IDA) and T cell costimulation. Supporting Evidence: PMID:9915850 Both CHO-CD80 and CHO-CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent transcriptional activation. |
| GO:0009986 cell surface | HDA PMID:23981064 Mycobacterium tuberculosis infection of human dendritic cell... | ACCEPT | Summary: HDA: CD86 detected at the surface of monocyte-derived dendritic cells by flow cytometry. Reason: Consistent with CD86 being a surface marker of APCs. Supporting Evidence: PMID:23981064 Notably, these cells are CD86 high , MHC class II high , CD11c high , CD1b + and CD14 − |
| GO:0015026 coreceptor activity | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | MODIFY | Summary: NAS: coreceptor activity. Reason: CD86 is the ligand (counter-receptor) on the APC; the coreceptor that cooperates with the TCR is CD28 on the T cell. The paper describes CD86 as a CD28 ligand, so the correct MF is receptor ligand activity (GO:0048018). Coreceptor activity mis-assigns the receptor role to the ligand. Proposed replacements: receptor ligand activity Supporting Evidence: PMID:9915850 Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. |
| GO:0032743 positive regulation of interleukin-2 production | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | KEEP AS NON CORE | Summary: NAS: CD86 costimulation enhances IL-2 production by T cells. Reason: Well supported (CHO-CD86 costimulates IL-2 and GM-CSF production; also PMID:7694363, PMID:7527824), but IL-2 production is a downstream readout of T cell costimulation rather than a separate core role. Supporting Evidence: PMID:9915850 ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production. PMID:7694363 B7-2 also costimulates IL-2 production and T cell proliferation. |
| GO:0032753 positive regulation of interleukin-4 production | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | UNDECIDED | Summary: NAS: positive regulation of IL-4 production. Reason: The abstract (full text not available) does not report IL-4; it only notes the hypothesis that CD80/CD86 skew Th1/Th2 responses. IL-4 data may be in the full text; cannot verify. Supporting Evidence: PMID:9915850 Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. |
| GO:0032761 positive regulation of lymphotoxin A production | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | UNDECIDED | Summary: NAS: positive regulation of lymphotoxin A production. Reason: Lymphotoxin is not mentioned in the available abstract (full text not cached). Possibly reported in the full text as one of the cytokines costimulated; cannot verify, and in any case a downstream readout of costimulation. Supporting Evidence: PMID:9915850 ligation of CD28 with either CD80 or CD86 leads to shared early signal transduction events such as the tyrosine phosphorylation of CBL and VAV, to NFAT-mediated transcriptional activation, and to the costimulation of interleukin-2 and granulocyte-macrophage colony-stimulating factor production. |
| GO:0038023 signaling receptor activity | TAS PMID:7694363 Cloning of B7-2: a CTLA-4 counter-receptor that costimulates... | MODIFY | Summary: TAS: signaling receptor activity. Reason: The paper names B7-2 a 'counter-receptor' of CD28/CTLA4, meaning it is the ligand for those receptors, not a signal-transducing receptor itself. Replace with receptor ligand activity (GO:0048018). (Mouse data suggest CD86 reverse signalling in B cells, but this is not shown in this paper.) Proposed replacements: receptor ligand activity Supporting Evidence: PMID:7694363 We have cloned a counter-receptor of CD28 and CTLA-4, termed B7-2. |
| GO:0042110 T cell activation | IDA PMID:7527824 CD80 (B7) and CD86 (B70) provide similar costimulatory signa... | MODIFY | Summary: IDA: CD86 transfectants costimulate T cell proliferation, cytokines and CTL generation. Reason: CD86 does not itself undergo or execute T cell activation; it supplies the second, antigen-independent signal to T cells. GO:0031295 T cell costimulation (is_a positive regulation of T cell activation) is defined as providing, via surface-bound receptor-ligand pairs, a second signal augmenting T cell activation — exactly what this paper shows. Comparator: CD80 carries GO:0031295. Proposed replacements: T cell costimulation Supporting Evidence: PMID:7527824 both CD80 and CD86 transfectants efficiently costimulated anti-CD3 mAb-induced proliferation and the secretion of IL-2 and IFN-gamma PMID:7527824 Results from these studies indicate that both CD80 and CD86 are potent and similar costimulators of T lymphocytes. |
| GO:0042113 B cell activation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Cd86: B cell activation (CD86 reverse signalling in B cells). Reason: Mouse data indicate CD86 engagement on B cells modulates B cell responses (NF-kB activation, IgG1). Plausible but secondary to its core T cell costimulatory ligand role. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Also involved in the regulation of B cells function, plays a role in regulating the level of IgG(1) produced. file:human/CD86/CD86-uniprot.txt Upon CD40 engagement, activates NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation |
| GO:0045630 positive regulation of T-helper 2 cell differentiation | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | MARK AS OVER ANNOTATED | Summary: NAS: positive regulation of T-helper 2 cell differentiation. Reason: The paper presents Th1/Th2 skewing by CD80 vs CD86 as a prevailing hypothesis ('is thought to') and speculates that signalling differences 'may contribute'; it does not show Th2 differentiation. The CD86-Th2 association remains context-dependent and contested. Supporting Evidence: PMID:9915850 Ligation of either CD80 (B7-1) or CD86 (B7-2), two principal ligands for CD28, is thought to skew the immune response toward Th1 or Th2 differentiation. PMID:9915850 These quantitative, if not qualitative, differences between signaling initiated by these two ligands for CD28 may contribute to functional differences (e.g. Th1 or Th2 differentiation) in T cell responses. |
| GO:0045893 positive regulation of DNA-templated transcription | NAS PMID:9915850 CD80 and CD86 are not equivalent in their ability to induce ... | MARK AS OVER ANNOTATED | Summary: NAS: positive regulation of DNA-templated transcription (NFAT-dependent reporter in T cells). Reason: NFAT-dependent transcription occurs in the responding T cell, many steps downstream of CD86 engagement of CD28. Annotating the extracellular ligand to generic transcription regulation is an over-extension; the relevant role is T cell costimulation. Supporting Evidence: PMID:9915850 Both CHO-CD80 and CHO-CD86, in the presence of anti-CD3 mAb, costimulated NFAT-dependent transcriptional activation. |
| GO:0046649 lymphocyte activation | IEA GO_REF:0000117 | MODIFY | Summary: ARBA IEA: lymphocyte activation. Reason: As for the T cell activation IDA, CD86 acts by providing a costimulatory signal; the specific process is T cell costimulation (GO:0031295). Proposed replacements: T cell costimulation Supporting Evidence: PMID:7694363 B7-2 also costimulates IL-2 production and T cell proliferation. |
| GO:0048018 receptor ligand activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: receptor ligand activity, inherited in the B7 family clade. Reason: Core MF: CD86 is the ligand for CD28 (stimulatory) and CTLA4 (inhibitory). Supporting Evidence: PMID:7694363 We have cloned a counter-receptor of CD28 and CTLA-4, termed B7-2. file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor file:human/CD86/CD86-deep-research-falcon.md CTLA-4 competes with CD28 for CD86 and can remove CD86 from APC surfaces, thereby reducing the ligand available for subsequent CD28 costimulation. |
| GO:0048018 receptor ligand activity | IDA PMID:11279501 Structural basis for co-stimulation by the human CTLA-4/B7-2... | ACCEPT | Summary: IDA: crystal structure of CTLA-4 bound to the B7-2 receptor-binding domain. Reason: Direct structural evidence of CD86 as ligand of CTLA4; core function. Supporting Evidence: PMID:11279501 the 3.2-A resolution structure of the complex between the disulphide-linked homodimer of human CTLA-4 and the receptor-binding domain of human B7-2 PMID:11279501 Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a stimulatory signal for T-cell activation |
| GO:0048018 receptor ligand activity | IDA PMID:12196291 The interaction properties of costimulatory molecules revisi... | ACCEPT | Summary: IDA: quantitative binding of B7-2 to CD28 and CTLA-4. Reason: Biophysical characterization of CD86 binding its receptors CD28 and CTLA4; core function. Supporting Evidence: PMID:12196291 B7-2 binds the two receptors more weakly than B7-1 PMID:12196291 relative to its CTLA-4 binding affinity, B7-2 binds CD28 2- to 3-fold more effectively than B7-1 |
| GO:0048018 receptor ligand activity | IDA PMID:24845157 CD80 and CD86 IgC domains are important for quaternary struc... | ACCEPT | Summary: IDA: CD86 domains required for receptor binding and co-signaling. Reason: Shows CD86 binds CD28/CTLA4 and delivers co-signal; core function. Supporting Evidence: PMID:24845157 CD86 and CD80, the ligands for the co-stimulatory molecules CD28 and CTLA-4, are members of the Ig superfamily. PMID:24845157 both IgC and intracellular domains are required for full co-signaling function. |
| GO:0050778 positive regulation of immune response | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA IEA: positive regulation of immune response. Reason: Broad but correct: CD86 costimulation promotes adaptive immune responses. Supporting Evidence: PMID:7694363 It is likely that B7-2 provides a critical early costimulatory signal determining if the T cell will contribute to an immune response or become anergic. |
| GO:0050862 positive regulation of T cell receptor signaling pathway | IDA PMID:11279501 Structural basis for co-stimulation by the human CTLA-4/B7-2... | ACCEPT | Summary: IDA: B7-2 engagement of CD28 augments TCR signalling. Reason: CD86-CD28 engagement provides the costimulatory signal that augments TCR-initiated signalling; curator-assigned from full text, consistent with the established biology. Supporting Evidence: PMID:11279501 Engagement of CD28 with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a stimulatory signal for T-cell activation |
| GO:0050862 positive regulation of T cell receptor signaling pathway | IDA PMID:12196291 The interaction properties of costimulatory molecules revisi... | ACCEPT | Summary: IDA: CD86 as CD28 ligand augments TCR signalling. Reason: Consistent with CD86's role as the CD28 ligand that augments the MHC/TCR signal. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Acts as the primary auxiliary signal augmenting the MHC/TCR signal in naive T-cells by acting as a ligand for the CD28 receptor |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: HDA: CD86 detected in B-cell-derived exosome proteome. Reason: APC-derived exosomes carry plasma membrane proteins including costimulatory molecules; this is a real but secondary location, likely passive cargo. Supporting Evidence: PMID:20458337 Professional antigen-presenting cells secrete major histocompatibility complex class II (MHC II) carrying exosomes with unclear physiological function(s). |
| GO:0070062 extracellular exosome | IDA PMID:15908444 Exosomal-like vesicles are present in human blood plasma. | KEEP AS NON CORE | Summary: IDA: CD86 on exosome-like vesicles in human plasma (per curator; abstract does not name CD86). Reason: The abstract describes MHC-bearing exosomes in plasma, consistent with APC origin; CD86 detection presumably in full text. Accept as non-core location. Supporting Evidence: PMID:15908444 We provide here the first evidence for the presence of exosomes in vivo, in the blood. |
| GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse Cd86: positive regulation of non-canonical NF-kB signal transduction in B cells. Reason: Mouse B-cell reverse-signalling data (UniProt By similarity); plausible but secondary to the core ligand function; human evidence lacking. Supporting Evidence: file:human/CD86/CD86-uniprot.txt Upon CD40 engagement, activates NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation |
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Download this section (compressed HTML)Q: Does human CD86 transduce 'reverse' signals into B cells or dendritic cells (as reported for mouse Cd86 regulating IgG1 and NF-kB), and if so which cytoplasmic-tail motifs and partners mediate it?
Q: What is the physiological contribution of the soluble/alternatively spliced CD86 isoforms (deltaTM, deltaEC, isoform 2) to tuning CD28 versus CTLA4 engagement in vivo?
Q: Should the CD86-CTLA4 relationship (CTLA4-mediated trans-endocytosis of CD86) be represented on CTLA4 (has input CD86) rather than as a process annotation on CD86?
Experiment: CRISPR knockout of CD86 versus CD80 in primary human monocyte-derived DCs, followed by co-culture with naive CD4 T cells to quantify the CD86-specific contribution to early IL-2 production and proliferation.
Experiment: Mutagenesis of the human CD86 cytoplasmic tail in B cells to test for cell-intrinsic signalling (NF-kB, IgG production) upon CD28-Ig or CTLA4-Ig engagement.
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