CD86
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Location (UCSC) | Chr 3: 122.06 – 122.12 Mb | Chr 16: 36.42 – 36.49 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Cluster of Differentiation 86 (also known as CD86 and B7-2) is a
The CD86
Structure
CD86 belongs to the
At the protein level, CD86 shares 25% identity with CD80[15] and both are coded on human chromosome 3q13.33q21.[16]
Role in co-stimulation, T-cell activation and inhibition
CD86 and CD80 bind as ligands to costimulatory molecule
The interaction between CD86 (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.[21] To become activated, lymphocyte must engage both antigen and costimulatory ligand on the same antigen-presenting cell. T cell receptor (TCR) interacts with major histocompatibility complex (MHC) class II molecules,[13] and this signalization must be accompanied by costimulatory signals, provided by a costimulatory ligand. These costimulatory signals are necessary to prevent anergy and are provided by the interaction between CD80/CD86 and CD28 costimulatory molecule.[22][23]
This protein interaction is also essential for T lymphocytes to receive the full activation signal, which in turn leads to T cell differentiation and division, production of interleukin 2 and clonal expansion.[9][22] Interaction between CD86 and CD28 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.[21] The interaction also regulates self-tolerance by supporting the homeostatis of CD4+CD25+ Tregulatory cell, also known as Tregs.[9]
CTLA-4 is a coinhibitory molecule that is induced on activated T cells. Interaction between CTLA-4 and CD80/CD86 leads to delivery of negative signals into T cells and reduction of number of costimulatory molecules on the cell surface. It can also trigger a signaling pathway responsible for expression of enzyme IDO (indolamine-2,3-dioxygenase). This enzyme can metabolize amino acid tryptophan, which is an important component for successful proliferation and differentiation of T lymphocytes. IDO reduces the concentration of tryptophan in the environment, thereby suppressing the activation of conventional T cells, while also promoting the function of regulatory T cells.[24][25]
Both CD80 and CD86 bind CTLA-4 with higher affinity than CD28. This allows CTLA-4 to outcompete CD28 for CD80/CD86 binding.[23][26] Between CD80 and CD86, CD80 appears to have a higher affinity for both CTLA-4 and CD28 than CD86. This suggest that CD80 is more potent ligand than CD86,[15] but studies using CD80 and CD86 knockout mice have shown that CD86 is more important in T cell activation than CD80.[27]
Treg mediation
Pathways in the B7:CD28 family have key roles in the regulation of T cell activation and tolerance. Their negative second signals are responsible for downregulation of cell responses. For all these reasons are these pathways considered as therapeutic targets.[9]
When bound to CTLA-4, CD86 can be removed from the surface of an APC and onto the Treg cell in a process called trogocytosis.[6] Blocking this process with anti-CTLA-4 antibodies is useful for a specific type of cancer immunotherapy called "Cancer therapy by inhibition of negative immune regulation".[31] 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.
Role in pathology
Roles of both CD80 and CD86 are studied in context of many pathologies. Selective inhibition of costimulatory inhibitors was examined in a model of allergic pulmonary inflammation and
See also
- Cluster of differentiation
- CD80
- CD28
- CTLA-4
- List of human clusters of differentiation for a list of CD molecules
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000114013 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022901 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 7504292.
- ^ PMID 31102428.
- S2CID 22260156.
- ^ "Entrez Gene: CD86 CD86 molecule".
- ^ PMID 15771580.
- PMID 21156796.
- PMID 7694362.
- S2CID 205492817.
- ^ )
- PMID 11012769.
- ^ PMID 12196291.
- )
- PMID 1847722.
- PMID 23024807.
- PMID 1714933.
- PMID 12810107.
- ^ PMID 28393361.
- ^ S2CID 20542148.
- ^ S2CID 20098311.
- PMID 23470321.
- PMID 15034022.
- S2CID 9617595.
- PMID 9075931.
- PMID 25582039.
- PMID 31130955.
- PMID 18635688.
- S2CID 201748060.
- PMID 9846693.
- PMID 29402722.
- S2CID 23564785.
- PMID 31102428.
- PMID 30792568.
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. 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. 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 (1): 98. 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. 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. 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. 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. 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. 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. PMID 20067533.
- Koyasu S (April 2003). "The role of PI3K in immune cells". Nature Immunology. 4 (4): 313–9. 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. S2CID 26024387.
- 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. 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. 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. 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. 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. 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. S2CID 3111709.
- 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. S2CID 24678182.
- 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. 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. PMID 20100932.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.