Cluster of differentiation 80 (also CD80 and B7-1) is a B7, type I membrane proteinthat is in the immunoglobulin superfamily, with an extracellular immunoglobulin constant-like domain and a variable-like domain required for receptor binding. It is closely related to CD86, another B7 protein (B7-2), and often works in tandem, binding to the same receptors to prime T cells.
|, B7, B7-1, B7.1, BB1, CD28LG, CD28LG1, LAB7, CD80 molecule|
CD80 can be found on the surface of various immune cells including dendritic cells, B cells, monocytes and antigen-presenting cells (APCs) and is the receptor for the proteins CD28 (for autoregulation and intercellular association) and CTLA-4 (for attenuation of regulation and cellular disassociation) found on the surface of T-cells. CD80 binds to CD28 and CTLA-4 with lower affinity and fast binding kinetics (Kd =4 µM), allowing for quick interactions between the communicating cells. This interaction results in an important costimulatory signal in the immunological synapse between antigen-presenting cells, B-cells, dendritic cells and T-cells that result in T and B-cell activation, proliferation and differentiation. CD80 is an especially important component in dendritic cell licensing and cytotoxic T-cell activation. When the major histocompatibility complex class II (MHC class II)- peptide complex on a dendritic cell interacts with the receptor on a T helper cell, CD80 is up-regulated, licensing the dendritic cell and allowing for interaction between the dendritic cell and [[CD 8+ T-cells]] via CD28. This helps to signal the T-cell differentiation into a cytotoxic T-cell.
CD80, often in tandem with CD86, plays a large and diverse role in the regulation of both the adaptive and the innate immune system. As mentioned above, this protein is very important for immune cell activation in response to pathogens. This activation occurs through stimulatory interaction with CD28, which can enhance cytokine production, and cell proliferation, and prevent apoptosis. CD80 interaction with CD28 also further stimulates dendritic cells, again enhancing cytokine production, specifically IL-6, a proinflammatory molecule. Neutrophils can also activate macrophages with CD80 viaCD28. In contrast to the stimulatory interaction with CD28, CD80 also regulates the immune system through an inhibitory interaction with CTLA-4. Dendritic cells have been found to be suppressed by a CTLA-4-CD80 interaction and this interaction also promotes the suppressive effects of regulatory T cells, which can prevent an immune response to self-antigen.
In addition to interactions with CD28 and CTLA-4, CD80 is also thought to interact with a separate ligand on Natural Killer cells, triggering the Natural Killer cell-mediated cell death of the CD80 carrier. CD80 may also play a role in the negative regulation of effector and memory T-cells. If the interaction between an antigen-presenting cell and a T-cell is stable enough, the T-cell can remove the CD80 from the antigen-presenting cell. Under the right conditions, this transfer of the CD80 may induce T-cell apoptosis. Finally, CD80 signaling on activated B-cells may regulate antibody secretion during infection.
The complicated role CD80 plays in immune system regulation presents an opportunity for CD80 interactions to go rogue in various diseases. The up-regulation of CD80 has been linked to various autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus and sepsis (which may partly be due to over-active T-cells), and CD80 has also been shown to help spread of HIV infection in the body. CD80 is also linked to various cancers, though some experience CD80 induced tolerance via possible regulatory T cell interaction and others experience inhibited growth and metastasis related to CD80 up-regulation, further exemplifying the complicated role CD80 plays.
The triggering of Natural Killer cell-mediated death via CD80 interactions has been explored as a possible cancer immunotherapy, through the induction of CD80 expression on tumor cells. Some therapies for autoimmune diseases involve the down-regulation of CD80, including the use of the immunosuppressants, resveratrol found in red grapes and curcumin found in turmeric.
- GRCh38: Ensembl release 89: ENSG00000121594 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000075122 - Ensembl, May 2017
- "Human PubMed Reference:".
- "Mouse PubMed Reference:".
- McKusick, V. A., & Converse, P. J. (2016, August 05). CD80 Antigen; CD80. Retrieved May 29, 2019
- Peach RJ, Bajorath J, Naemura J, Leytze G, Greene J, Aruffo A, Linsley PS (September 1995). "Both extracellular immunoglobin-like domains of CD80 contain residues critical for binding T cell surface receptors CTLA-4 and CD28". The Journal of Biological Chemistry. 270 (36): 21181–7. doi:10.1074/jbc.270.36.21181. PMID 7545666.
- Owen JA, Punt J, Stranford SA, Jones PP, Kuby J (2013). Kuby Immunology (7th ed.). New York: W.H. Freeman and Company.
- van der Merwe PA, Bodian DL, Daenke S, Linsley P, Davis SJ (February 1997). "CD80 (B7-1) binds both CD28 and CTLA-4 with a low affinity and very fast kinetics". The Journal of Experimental Medicine. 185 (3): 393–403. doi:10.1084/jem.185.3.393. PMC 2196039. PMID 9053440.
- Fujii S, Liu K, Smith C, Bonito AJ, Steinman RM (June 2004). "The linkage of innate to adaptive immunity via maturing dendritic cells in vivo requires CD40 ligation in addition to antigen presentation and CD80/86 costimulation". The Journal of Experimental Medicine. 199 (12): 1607–18. doi:10.1084/jem.20040317. PMC 2212806. PMID 15197224.
- Zheng Y, Manzotti CN, Liu M, Burke F, Mead KI, Sansom DM (March 2004). "CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells". Journal of Immunology. Baltimore, Md. 172 (5): 2778–84. doi:10.4049/jimmunol.172.5.2778. PMID 14978077.
- Orabona C, Grohmann U, Belladonna ML, Fallarino F, Vacca C, Bianchi R, Bozza S, Volpi C, Salomon BL, Fioretti MC, Romani L, Puccetti P (November 2004). "CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86". Nature Immunology. 5 (11): 1134–42. doi:10.1038/ni1124. PMID 15467723.
- Nolan A, Kobayashi H, Naveed B, Kelly A, Hoshino Y, Hoshino S, Karulf MR, Rom WN, Weiden MD, Gold JA (August 2009). "Differential role for CD80 and CD86 in the regulation of the innate immune response in murine polymicrobial sepsis". PLOS ONE. 4 (8): e6600. Bibcode:2009PLoSO...4.6600N. doi:10.1371/journal.pone.0006600. PMC 2719911. PMID 19672303.
- Chambers BJ, Salcedo M, Ljunggren HG (October 1996). "Triggering of natural killer cells by the costimulatory molecule CD80 (B7-1)". Immunity. 5 (4): 311–7. doi:10.1016/S1074-7613(00)80257-5. PMID 8885864.
- Sabzevari H, Kantor J, Jaigirdar A, Tagaya Y, Naramura M, Hodge J, Bernon J, Schlom J (February 2001). "Acquisition of CD80 (B7-1) by T cells". Journal of Immunology (Baltimore, Md. : 1950). 166 (4): 2505–13. doi:10.4049/jimmunol.166.4.2505. PMID 11160311.
- Rau FC, Dieter J, Luo Z, Priest SO, Baumgarth N (December 2009). "B7-1/2 (CD80/CD86) direct signaling to B cells enhances IgG secretion". Journal of Immunology (Baltimore, Md. : 1950). 183 (12): 7661–71. doi:10.4049/jimmunol.0803783. PMC 2795108. PMID 19933871.
- Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA (December 1995). "Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions". The Journal of Experimental Medicine. 182 (6): 1985–96. doi:10.1084/jem.182.6.1985. PMC 2192240. PMID 7500044.
- Wong CK, Lit LC, Tam LS, Li EK, Lam CW (August 2005). "Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and CD86 in patients with systemic lupus erythematosus". Rheumatology. Oxford, England. 44 (8): 989–94. doi:10.1093/rheumatology/keh663. PMID 15870153.
- Nolan A, Weiden M, Kelly A, Hoshino Y, Hoshino S, Mehta N, Gold JA (February 2008). "CD40 and CD80/86 act synergistically to regulate inflammation and mortality in polymicrobial sepsis". American Journal of Respiratory and Critical Care Medicine. 177 (3): 301–8. doi:10.1164/rccm.200703-515OC. PMC 2218847. PMID 17989345.
- Pinchuk LM, Polacino PS, Agy MB, Klaus SJ, Clark EA (July 1994). "The role of CD40 and CD80 accessory cell molecules in dendritic cell-dependent HIV-1 infection". Immunity. 1 (4): 317–25. doi:10.1016/1074-7613(94)90083-3. PMID 7534204.
- Yang R, Cai Z, Zhang Y, Yutzy WH, Roby KF, Roden RB (July 2006). "CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells". Cancer Research. 66 (13): 6807–15. doi:10.1158/0008-5472.CAN-05-3755. PMID 16818658.
- Imasuen I, Bozeman E, He S, Patel J, Selvaraj P (May 2013). "Increased B7-1 (CD80) expression reduces overall tumorigenicity and metastatic potential of the murine pancreatic cancer cell model Pan02 (P2085)". The Journal of Immunology. 190 (1 Supplement).
- Sharma S, Chopra K, Kulkarni SK, Agrewala JN (January 2007). "Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway". Clinical and Experimental Immunology. 147 (1): 155–63. doi:10.1111/j.1365-2249.2006.03257.x. PMC 1810449. PMID 17177975.