CD86

Cluster of Differentiation 86 (also known as CD86 and B7-2) is a protein expressed on dendritic cells, macrophages, B-cells, and other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals necessary for T-cell activation and survival. Depending on the ligand bound, CD86 can be used to signal for self-regulation and cell-cell association, or for attenuation of regulation and cell-cell disassociation.[5]

This article is about the molecule. For the compilation album, see CD86 (album).

CD86
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1I85, 1NCN
Identifiers
Aliases	CD86, B7-2, B7.2, B70, CD28LG2, LAB72, CD86 molecule
External IDs	OMIM: 601020 MGI: 101773 HomoloGene: 10443 GeneCards: CD86
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 122,055,362 bp[1] End 122,121,139 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16 B3|16 25.72 cM Start 36,603,869 bp[2] End 36,666,081 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • coreceptor activity • virus receptor activity • GO:0001948 protein binding • receptor binding • receptor activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity • signaling receptor activity Cellular component • integral component of membrane • intracellular membrane-bounded organelle • membrane • cell membrane • cell surface • extracellular exosome • external side of plasma membrane Biological process • response to yeast • adaptive immune response • response to interferon-gamma • immune system process • cell-cell signaling • T cell costimulation • aging • myeloid dendritic cell differentiation • cellular response to cytokine stimulus • T cell proliferation involved in immune response • positive regulation of interleukin-2 biosynthetic process • toll-like receptor signaling pathway • positive regulation of transcription, DNA-templated • B cell activation • response to lipopolysaccharide • cellular response to metal ion • negative regulation of T cell anergy • defense response to virus • immune response • positive regulation of T cell proliferation • positive regulation of cell proliferation • positive regulation of T-helper 2 cell differentiation • viral entry • GO:0022415 viral process • positive regulation of lymphotoxin A biosynthetic process • toll-like receptor 3 signaling pathway • cellular response to lipopolysaccharide • T cell activation • response to drug • positive regulation of interleukin-4 biosynthetic process • positive regulation of activated T cell proliferation • phosphatidylinositol phosphorylation • positive regulation of protein kinase B signaling • signal transduction • cell surface receptor signaling pathway • cytokine-mediated signaling pathway • negative regulation of T cell proliferation Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	942	12524
Ensembl	ENSG00000114013	ENSMUSG00000022901
UniProt	P42081	P42082
RefSeq (mRNA)	NM_176892 NM_001206924 NM_001206925 NM_006889 NM_175862	NM_019388
RefSeq (protein)	NP_001193853 NP_001193854 NP_008820 NP_787058 NP_795711	NP_062261
Location (UCSC)	Chr 3: 122.06 – 122.12 Mb	Chr 16: 36.6 – 36.67 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

The CD86 gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily.[6] Alternative splicing results in two transcript variants encoding different isoforms. Additional transcript variants have been described, but their full-length sequences have not been determined.[7]

Co-stimulation for T-cell activation

The binding of CD86 (or the closely related protein CD80) expressed on the surface of an antigen-presenting cell with CD28 on the surface of a mature, naive T-cell, is required for T-cell activation.[8] This protein interaction, along with the primary signal that is the MHC class II with an attached peptide binding to the T-cell receptor (TCR), activates mitogen-activated protein kinase and transcription factor nf-κB in the T-cell. These proteins up-regulate production of CD40L (used in B-cell activation), IL-21 and IL-21R (used for division/proliferation), and IL-2, among other cytokines.[8]

T-reg mediation

CTLA-4 inhibits CD86 - CD28 binding when active on T-regulatory cells

T-regulatory cells produce CTLA-4, which can dampen an immune response and lead to increased anergy.[5] CTLA-4 binds to CD86 with greater affinity than CD28, which impairs the co-stimulation necessary for proper T-cell activation.[9] When bound to CTLA-4, CD86 can be removed from the surface of an APC and onto the T-reg cell in a process called trogocytosis.[5] Blocking this process with anit-CTLA-4 antibodies is useful for a specific type of cancer immunotherapy called cancer therapy by inhibition of negative immune regulation.[10] Japanese immunologist Tasuku Honjo and American immunologist James P. Allison won the Nobel Prize in Physiology or Medicine in 2018 for their work on this topic.

See also

• Cluster of differentiation
• CD80
• CD28
• CTLA-4
• List of human clusters of differentiation for a list of CD molecules

References

1. GRCh38: Ensembl release 89: ENSG00000114013 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022901 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Ohue Y, Nishikawa H (July 2019). "Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?". Cancer Science. 110 (7): 2080–2089. doi:10.1111/cas.14069. PMC 6609813. PMID 31102428.
6. Chen C, Gault A, Shen L, Nabavi N (May 1994). "Molecular cloning and expression of early T cell costimulatory molecule-1 and its characterization as B7-2 molecule". Journal of Immunology. 152 (10): 4929–36. PMID 7513726.
7. "Entrez Gene: CD86 CD86 molecule".
8. Dyck L, Mills KH (May 2017). "Immune checkpoints and their inhibition in cancer and infectious diseases". European Journal of Immunology. 47 (5): 765–779. doi:10.1002/eji.201646875. PMID 28393361.
9. Lightman SM, Utley A, Lee KP (2019-05-03). "Survival of Long-Lived Plasma Cells (LLPC): Piecing Together the Puzzle". Frontiers in Immunology. 10: 965. doi:10.3389/fimmu.2019.00965. PMC 6510054. PMID 31130955.
10. Chen R, Ganesan A, Okoye I, Arutyunova E, Elahi S, Lemieux MJ, Barakat K (March 2020). "Targeting B7-1 in immunotherapy". Medicinal Research Reviews. 40 (2): 654–682. doi:10.1002/med.21632. PMID 31448437.

External links

• Human CD86 genome location and CD86 gene details page in the UCSC Genome Browser.

Further reading

• Davila S, Froeling FE, Tan A, Bonnard C, Boland GJ, Snippe H, et al. (April 2010). "New genetic associations detected in a host response study to hepatitis B vaccine". Genes and Immunity. 11 (3): 232–8. doi:10.1038/gene.2010.1. PMID 20237496.
• Csillag A, Boldogh I, Pazmandi K, Magyarics Z, Gogolak P, Sur S, et al. (March 2010). "Pollen-induced oxidative stress influences both innate and adaptive immune responses via altering dendritic cell functions". Journal of Immunology. 184 (5): 2377–85. doi:10.4049/jimmunol.0803938. PMC 3028537. PMID 20118277.
• Bossé Y, Lemire M, Poon AH, Daley D, He JQ, Sandford A, et al. (October 2009). "Asthma and genes encoding components of the vitamin D pathway". Respiratory Research. 10: 98. doi:10.1186/1465-9921-10-98. PMC 2779188. PMID 19852851.
• Mosbruger TL, Duggal P, Goedert JJ, Kirk GD, Hoots WK, Tobler LH, et al. (May 2010). "Large-scale candidate gene analysis of spontaneous clearance of hepatitis C virus". The Journal of Infectious Diseases. 201 (9): 1371–80. doi:10.1086/651606. PMC 2853721. PMID 20331378.
• Bugeon L, Dallman MJ (October 2000). "Costimulation of T cells". American Journal of Respiratory and Critical Care Medicine. 162 (4 Pt 2): S164-8. doi:10.1164/ajrccm.162.supplement_3.15tac5. PMID 11029388.
• Pan XM, Gao LB, Liang WB, Liu Y, Zhu Y, Tang M, et al. (July 2010). "CD86 +1057 G/A polymorphism and the risk of colorectal cancer". DNA and Cell Biology. 29 (7): 381–6. doi:10.1089/dna.2009.1003. PMID 20380573.
• Dalla-Costa R, Pincerati MR, Beltrame MH, Malheiros D, Petzl-Erler ML (August 2010). "Polymorphisms in the 2q33 and 3q21 chromosome regions including T-cell coreceptor and ligand genes may influence susceptibility to pemphigus foliaceus". Human Immunology. 71 (8): 809–17. doi:10.1016/j.humimm.2010.04.001. PMID 20433886.
• Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, et al. (November 2009). "Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip". American Journal of Human Genetics. 85 (5): 628–42. doi:10.1016/j.ajhg.2009.10.014. PMC 2775832. PMID 19913121.
• Carreño LJ, Pacheco R, Gutierrez MA, Jacobelli S, Kalergis AM (November 2009). "Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fc gamma receptors and costimulatory molecules on dendritic cells". Immunology. 128 (3): 334–41. doi:10.1111/j.1365-2567.2009.03138.x. PMC 2770681. PMID 20067533.
• Koyasu S (April 2003). "The role of PI3K in immune cells". Nature Immunology. 4 (4): 313–9. doi:10.1038/ni0403-313. PMID 12660731. S2CID 9951653.
• Kim SH, Lee JE, Kim SH, Jee YK, Kim YK, Park HS, et al. (December 2009). "Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions". Clinical and Experimental Allergy. 39 (12): 1852–6. doi:10.1111/j.1365-2222.2009.03336.x. PMID 19735272.
• Liu Y, Liang WB, Gao LB, Pan XM, Chen TY, Wang YY, et al. (November 2010). "CTLA4 and CD86 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease". Human Immunology. 71 (11): 1141–6. doi:10.1016/j.humimm.2010.08.007. PMID 20732370.
• Ma XN, Wang X, Yan YY, Yang L, Zhang DL, Sheng X, et al. (June 2010). "Absence of association between CD86 +1057G/A polymorphism and coronary artery disease". DNA and Cell Biology. 29 (6): 325–8. doi:10.1089/dna.2009.0987. PMID 20230296.
• Ishizaki Y, Yukaya N, Kusuhara K, Kira R, Torisu H, Ihara K, et al. (April 2010). "PD1 as a common candidate susceptibility gene of subacute sclerosing panencephalitis". Human Genetics. 127 (4): 411–9. doi:10.1007/s00439-009-0781-z. PMID 20066438. S2CID 12633836.
• Chang TT, Kuchroo VK, Sharpe AH (2002). "Role of the B7-CD28/CTLA-4 pathway in autoimmune disease". Current Directions in Autoimmunity. 5: 113–30. doi:10.1159/000060550. ISBN 3-8055-7308-1. PMID 11826754.
• Grujic M, Bartholdy C, Remy M, Pinschewer DD, Christensen JP, Thomsen AR (August 2010). "The role of CD80/CD86 in generation and maintenance of functional virus-specific CD8+ T cells in mice infected with lymphocytic choriomeningitis virus". Journal of Immunology. 185 (3): 1730–43. doi:10.4049/jimmunol.0903894. PMID 20601595.
• Quaranta MG, Mattioli B, Giordani L, Viora M (November 2006). "The immunoregulatory effects of HIV-1 Nef on dendritic cells and the pathogenesis of AIDS". FASEB Journal. 20 (13): 2198–208. doi:10.1096/fj.06-6260rev. PMID 17077296.
• Schuurhof A, Bont L, Siezen CL, Hodemaekers H, van Houwelingen HC, Kimman TG, et al. (June 2010). "Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls". Pediatric Pulmonology. 45 (6): 608–13. doi:10.1002/ppul.21229. PMID 20503287.
• Bailey SD, Xie C, Do R, Montpetit A, Diaz R, Mohan V, et al. (October 2010). "Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study". Diabetes Care. 33 (10): 2250–3. doi:10.2337/dc10-0452. PMC 2945168. PMID 20628086.
• Radziewicz H, Ibegbu CC, Hon H, Bédard N, Bruneau J, Workowski KA, et al. (March 2010). "Transient CD86 expression on hepatitis C virus-specific CD8+ T cells in acute infection is linked to sufficient IL-2 signaling". Journal of Immunology. 184 (5): 2410–22. doi:10.4049/jimmunol.0902994. PMC 2924663. PMID 20100932.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.