CD86 B7-2, B70
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Germinal Center
Dendritic Cell
Peripheral blood
Centrocyte
Endothelial Cell
B Cell
Monocyte
T Cell
80 / 80

Expression
CD86 is expressed constitutively on interdigitating dendritic cells in T zones of secondary lymphoid organs and at lower levels on Langerhans cells and peripheral blood dendritic cells.  It is expressed on memory B cells and germinal center B cells. Centrocytes express more CD86 than centroblasts. Small sIgD+, IgM+ tonsil B cells do not express CD86 but can be induced to express high levels of this molecule on activation in vitro through their surface immunoglobulin, CD40, MHC class II molecules or by phorbol myristate acetate with ionomycin.  These signals also upregulate the expression of CD86 on memory B cells and germinal center (GC) B cells.  CD86 has also been reported at low levels on monocytes and this expression is increased by culture with IFNg.  Endothelial and T cells activated by C3 ligation have also been reported to express CD86.  CD86 is a co-regulator of T cell activation with CD80.  Many T cell clones express both CD86 and CD80.  Expression is increased on IL-4 B cells and IFNg stimulated peripheral blood monocytes and is decreased by IL-10 on peripheral blood dendritic cells.



Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.

CD86 is a single-chain type-1 323 aa glycoprotein.  It contains a 224 aa extracellular domains which contains 1 Ig-like V-type domains and 1 Ig-like C2-type domain, a 21 aa transmembrane domain and a 61 aa cytoplasmic domain which has 3 potential sites for protein kinase C phosphorylation.  CD86 is structurally related to CD80 with a 25% aa identity and functions as a counter receptor for the T-cell accessory molecules CD28 and CD152.  The transmembrane domain contains 2 of the 3 cysteines seen in CD80.  The cytoplasmic domain is completely unrelated to the CD80 cytoplasmic domain and contains 3 potential protein kinase C phosphorylation sites.

MOLECULAR MASS
Cell Type Unreduced Reduced
Raji 80 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD86 is a glycoprotein with N-linked carbohydrates. 


Ligands
Like CD80, the extracellular portion of CD86 binds to CD28 and CD152 (CTLA-4). Like CD80, CD86 binds CD28 with a lower avidity than CD152, and binding involves residues in the V-domain.  CD86 binds CD152 with a lower avidity than CD80.

LIGANDS AND MOLECULES ASSOCIATED WITH CD86
Molecule Comment
CD28 CD86 is a ligand for both CD28 and CD152 (CTLA-4), and binds to the latter with a 20-100-fold higher affinity than to CD28. Although CD80 (B7-1) shares the same coreceptors as CD86, the on/off binding rates of CD86 for CD152 (CTLA-4) are higher than those of CD80. No potential cytoplasmic or surface signaling molecules have yet been identified that associate with CD86 in CD86-expressing cells
CD152 (CTLA-4) CD86 is a ligand for both CD28 and CD152 (CTLA-4), and binds to the latter with a 20-100-fold higher affinity than to CD28. Although CD80 (B7-1) shares the same coreceptors as CD86, the on/off binding rates of CD86 for CD152 (CTLA-4) are higher than those of CD80. No potential cytoplasmic or surface signaling molecules have yet been identified that associate with CD86 in CD86-expressing cells



Function
CD86 co-stimulates IL-2 production and T cell proliferation and activation.  CD86 acts as one of the ligands for the T cell co-stimulatory molecule CD28.  As described, CD86 also binds to CD152 (CTLA4), a molecule that has been reported to transduce a negative signal to the T cell.  Blockade of CD28 binding to CD86 by CD86 antibodies has been reported to bias the CD28-expressing T cell towards a Th1 cell, whereas blockage of CD28 ligation to CD80 polarizes the T cell into a Th2 cell.  CD80 and CD86 appear to have similar but not identical effects on cells expressing CD28 and on the induction of tyrosine phosphorylation.  Activation of phospholipase C, sphingomyelinase and phosphatidylinositol 3 kinase (PI-3 kinase) have all been reported.  While activation of PI-3 kinase by CD80 crosslinking is inhibited by a much lower dose of worthmannin than that required to block CD86 crosslinking.

BIOCHEMICAL ACTIVITY

Signaling through human CD86 has not been demonstrated but there are 3 potential sites for protein kinase C-dependent phosphorylation on its cytoplasmic tail.  The lack of homology between the cytoplasmic tails of murine and human CD86 throws some doubt on the significance of these phosphorylation sites.

DISEASE RELEVANCE AND FUNCTION OF CD86 IN INTACT ANIMAL

Signaling through CD28 and CD152 by engagement of CD80 and CD86 has a critical role in the induction and regulation of immune responses.  There is a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma.  A soluble form of CD86 encoded by an alternatively spliced transcript is present at elevated levels in blood in some leukemia patients.  The critical role of CD86s has been demonstrated dramatically by blocking CD80 and CD86 with soluble CD152 encoded by a transgene. These mice have impaired Ig class-switching and germinal center formation.  CD86 knockout mice have deficient antibody responses comparable to that seen with soluble CD152 Fcg Ig-transgenics while CD80 knockout mice give apparently normal antibody responses.  Knockout of CD28 genes causes an effect similar to that seen in the soluble CD152 transgenic mice, while CD152 knockout mice have increased T cell reactivity and develop T lymphoproliferative disease.  In vivo blocking of CD28 ligation with the CTLA4-Ig construct enhances the survival of allografts, although it does not prevent long-term rejections.  A putative role for both CD80 and CD86 in the treatment of neoplasia has also been investigated.  Some but not all CD86 transfected tumors have been reported to induce a successful anti-tumor immune response in vivo.  Blockade of CD28 signaling may also have a role in treatment of autoimmune diseases.  Injection of the CTLA4-Ig construct in either NOD mice, used as a model for insulin-dependent diabetes, or NZB/NZW F1 mice, a model for systemic lupus erythematosus, resulted in a decrease in the production of autoantibodies.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD86: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD86: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 942P42081
MouseP42082L25606
Antibodies
BU63   View Reactivity
FUN-1   View Reactivity
HA5.2B7   View Reactivity
IT2.2   View Reactivity

Revised June 25, 2008


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