• B7-2
• B70

MAJOR LINKS FOR CD86  

• NCBI LocusLink Record: 942
• Mendelian Inheritance in Man (OMIM): 601020
• SwissProt annotated protein record: P42081

• Signaling through human CD86 to the cells that express it has not been demonstrated to date, but the three potential sites for protein kinase C-dependent phosphorylation on its cytoplasmic tail suggest that this may occur
• On the other hand the lack of homology between the cytoplasmic tails of murine and human CD86 throws some doubt on the significance of these phosphorylation sites

CELLULAR FUNCTION OF CD86  

• CD86 acts as one of the ligands for the T cell co-stimulatory molecule CD28 (reviewed in June et al. 1994)
• As described above CD86 also binds to CD152 (CTLA4), a molecule that has been reported to transduce a negative signal to the T cell (Walunas et al. 1994)
• Blockade of CD28 binding to CD86 by CD86 antibodies has been reported to bias the CD28-expressing T cell towards a Th1 cell, whereas blockade of CD28 ligation to CD80 polarizes the T cell into a Th2 cell (Kuchroo et al. 1995)
• CD80 and CD86 appear to have similar but not identical effects on cells expressing CD28; induction of tyrosine phosphorylation, and activation of phospholipase C, sphingomyelinase and phosphatidylinositol 3 kinase have all been reported. While activation of phosphatidylinositol 3 kinase by CD80 cross-linking is inhibited by a much lower dose of worthmannin than that required to block CD86 cross-linking (Ueda et al. 1995)

DISEASE RELEVANCE OF CD86 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
• 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 (Ronchese et al. 1994)
• CD86 knockout mice (Borriello et al 1997) have deficient antibody responses comparable to that seen with soluble CD152 Fc-gamma Ig-transgenics while CD80 knockout mice give apparently normal antibody responses
• Knock-out of CD28 genes causes an effect similar to that seen in the soluble CD152 transgenic mice, while CD152 knock-out mice have increased T cell reactivity and develop T lymphoproliferative disease (reviewed in Lenschow et al. 1996 and Hathcock et al. 1996)
• In vivo blocking of CD28 ligation with the CTLA4-Ig construct enhances the survival of allografts, although it does not prevent long-term rejections (Lenschow et al. 1992)
• A putative role for both CD80 and CD86 in the treatment of neoplasia has also been investigated. Some but by no means all CD86 transfected tumors have been reported to induce a successful anti-tumor immune response in vivo (Townsend et al. 1994)
• 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 (model for systemic lupus erythematosus) resulted in a decrease in the production of autoantibodies (reviewed in Lenschow et al. 1996 and Hathcock et al. 1996)

• Families in which CD86 is a member
  • CD86-->immunoglobulin supergene family

MOLECULAR STRUCTURE OF CD86  

• The CD86 cDNA encodes for a 323 amino-acid polypeptide
• CD86 is a single chain with extracellular and transmembrane domains, and a cytoplasmic tail
• The extracellular region contains a single Ig V-like and a single Ig C2-like domain and eight sites for N-glycosylation (Azuma et al. 1993, Freeman et al. 1993)

MOLECULAR MASS OF CD86  

POST-TRANSCRIPTIONAL MODIFICATION OF CD86   - No information

POST-TRANSLATIONAL MODIFICATION OF CD86  

• It is a glycoprotein with N-linked carbohydrates (Azuma et al 1993)
• The cytoplasmic tail has 3 potential sites for protein kinase C phosphorylation

SUBSTRATES FOR CD86   - None reported

ENZYMES WHICH MODIFY CD86   - None reported

LIGANDS FOR CD86 AND MOLECULES ASSOCIATED WITH CD86  

• Note 1- 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 (Linsley et al. 1994)
• Although CD80 (B7-1) shares the same co-receptors as CD86, the on/off binding rates of CD86 for CD152 (CTLA-4) are higher than those of CD80 (Azuma et al. 1993, Freeman et al. 1993)
• No potential cytoplasmic or surface signaling molecules have yet been identified that associate with CD86 in CD86-expressing cells

• CD86 is expressed constitutively by interdigitating dendritic cells in T zones of secondary lymphoid organs and at lower levels by Langerhans cells and peripheral blood dendritic cells
• It is expressed by 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 up-regulate the expression of CD86 on memory B cells and GC B cells
• CD86 has also been reported to be expressed at low levels by monocytes and this expression is increased by culture with g-interferon
• Endothelial cells (Seino et al. 1995), and T cells activated by CD3 ligation have also been reported to express CD86 (Das et al. 1995);
• Many T cell clones express both CD86 and CD80

SELECTION OF OTHER CD86-SPECIFIC REFERENCE MAB  

REVIEWS

1. Hathcock KS,Hodes RJ Role of the CD28-B7 costimulatory pathways in T cell-dependent B cell responses. Adv Immunol 1996 62:131 PubMed

2. June CH,Bluestone JA,Nadler LM,Thompson CB The B7 and CD28 receptor families. Immunol Today 1994 15:321 PubMed

3. Lenschow DJ,Walunas TL,Bluestone JA CD28/B7 system of T cell costimulation. Annu Rev Immunol 1996 14:233 PubMed

4. Townsend SE,Su FW,Atherton JM,Allison JP Specificity and longevity of antitumor immune responses induced by B7- transfected tumors. Cancer Res 1994 54:6477 PubMed

PRIMARY CITATIONS

5. Azuma M,Ito D,Yagita H,Okumura K,Phillips JH,Lanier LL,Somoza C B70 antigen is a second ligand for CTLA-4 and CD28. Nature 1993 366:76 PubMed

6. Borriello F,Sethna MP,Boyd SD,Schweitzer AN,Tivol EA,Jacoby D,Strom TB,Simpson EM,Freeman GJ,Sharpe AH B7-1 and B7-2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity 1997 6:303 PubMed

7. Freeman GJ,Gribben JG,Boussiotis VA,Ng JW,Restivo VA Jr,Lombard LA,Gray GS,Nadler LM Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 1993 262:909 PubMed

8. Kuchroo VK,Das MP,Brown JA,Ranger AM,Zamvil SS,Sobel RA,Weiner HL,Nabavi N,Glimcher LH B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995 80:707 PubMed

9. Lenschow DJ,Zeng Y,Thistlethwaite JR,Montag A,Brady W,Gibson MG,Linsley PS,Bluestone JA Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4lg. Science 1992 257:789 PubMed

10. Linsley PS,Greene JL,Brady W,Bajorath J,Ledbetter JA,Peach R Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1994 1:793 PubMed

11. Prabhu Das MR,Zamvil SS,Borriello F,Weiner HL,Sharpe AH,Kuchroo VK Reciprocal expression of co-stimulatory molecules, B7-1 and B7-2, on murine T cells following activation. Eur J Immunol 1995 25:207 PubMed

12. Ronchese F,Hausmann B,Hubele S,Lane P Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo. J Exp Med 1994 179:809 PubMed

13. Seino K,Azuma M,Bashuda H,Fukao K,Yagita H,Okumura K CD86 (B70/B7-2) on endothelial cells co-stimulates allogeneic CD4+ T cells. Int Immunol 1995 7:1331 PubMed

14. Ueda Y,Levine BL,Huang ML,Freeman GJ,Nadler LM,June CH,Ward SG Both CD28 ligands CD80 (B7-1) and CD86 (B7-2) activate phosphatidylinositol 3-kinase, and wortmannin reveals heterogeneity in the regulation of T cell IL-2 secretion. Int Immunol 1995 7:957 PubMed

15. Walunas TL,Lenschow DJ,Bakker CY,Linsley PS,Freeman GJ,Green JM,Thompson CB,Bluestone JA CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994 1:405 PubMed

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Modified 10/14/99   mpr@mail.nih.gov