CD83: Difference between revisions
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== Function == |
== Function == |
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The main function of membrane-bound CD83 is stabilization of [[MHC II|MHC II.]], [[Costimulation|costimulatory molecules]] and [[CD28]] in membrane by its transmembrane domain antagonistic activity to MARCH family [[E3 Ubiquitin Ligase|E3 ubiquitin ligases]]<ref>{{cite journal |last1=von Rohrscheidt |first1=Julia |last2=Petrozziello |first2=Elisabetta |last3=Nedjic |first3=Jelena |last4=Federle |first4=Christine |last5=Krzyzak |first5=Lena |last6=Ploegh |first6=Hidde L. |last7=Ishido |first7=Satoshi |last8=Steinkasserer |first8=Alexander |last9=Klein |first9=Ludger |title=Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83 |journal=Journal of Experimental Medicine |date=22 August 2016 |volume=213 |issue=9 |pages=1685–1694 |doi=10.1084/jem.20160316}}</ref>. |
The main function of membrane-bound CD83 is stabilization of [[MHC II|MHC II.]], [[Costimulation|costimulatory molecules]] and [[CD28]] in membrane by its transmembrane domain antagonistic activity to MARCH family [[E3 Ubiquitin Ligase|E3 ubiquitin ligases]]<ref>{{cite journal |last1=Grosche |first1=Linda |last2=Knippertz |first2=Ilka |last3=König |first3=Christina |last4=Royzman |first4=Dmytro |last5=Wild |first5=Andreas B. |last6=Zinser |first6=Elisabeth |last7=Sticht |first7=Heinrich |last8=Muller |first8=Yves A. |last9=Steinkasserer |first9=Alexander |last10=Lechmann |first10=Matthias |title=The CD83 Molecule – An Important Immune Checkpoint |journal=Frontiers in Immunology |date=17 April 2020 |volume=11 |pages=721 |doi=10.3389/fimmu.2020.00721}}</ref><ref>{{cite journal |last1=von Rohrscheidt |first1=Julia |last2=Petrozziello |first2=Elisabetta |last3=Nedjic |first3=Jelena |last4=Federle |first4=Christine |last5=Krzyzak |first5=Lena |last6=Ploegh |first6=Hidde L. |last7=Ishido |first7=Satoshi |last8=Steinkasserer |first8=Alexander |last9=Klein |first9=Ludger |title=Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83 |journal=Journal of Experimental Medicine |date=22 August 2016 |volume=213 |issue=9 |pages=1685–1694 |doi=10.1084/jem.20160316}}</ref>. |
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=== Ligands === |
=== Ligands === |
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It is not clear what ligands interact with CD83 but it looks like that membrane-bound CD83 homotypicaly interacts with soluble form may suggest [[Autocrine signaling|autocrine]] immune regulation. However, it contrasts with differences between the single expression of soluble CD83 on [[monocytes]] and membrane CD83 on activated DCs. Soluble CD83 also binds to [[CD153]] leading to supports Th2 T lymphocytes [[apoptosis]] by suppression of [[Bcl-2 inhibitor|BCL inhibitors]]. |
It is not clear what ligands interact with CD83 but it looks like that membrane-bound CD83 homotypicaly interacts with soluble form may suggest [[Autocrine signaling|autocrine]] immune regulation. However, it contrasts with differences between the single expression of soluble CD83 on [[monocytes]] and membrane CD83 on activated DCs. Soluble CD83 also binds to [[CD153]] leading to supports Th2 T lymphocytes [[apoptosis]] by suppression of [[Bcl-2 inhibitor|BCL inhibitors]]. |
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Revision as of 06:40, 29 April 2021
 | This article may require copy editing for grammar, style, cohesion, tone, or spelling. (April 2021) |
CD83 (Cluster of Differentiation 83) is a human protein encoded by the CD83 gene.[5]
Structure
CD83 is present as membrane-bound protein as same as soluble form. Extracellularly it is composed of V-type immunoglobulin like domain and in the case of membrane-bound form, it is also present as transmembrane domain and signaling cytoplasmic tail. Membrane-bound CD83 presumably forms trimers. Soluble CD83 is able to create dodecameric complexes.[6]
Gene
CD83 gene is localized in human chromosome 6p23 and in mice on chromosome 13. In humans, promoter is localized 261bp upstream obtains five NFκB and three IRFs binding sites showing the importance of CD83 during inflammation conditions[7] and moreover binding sites for AhR in promotor sequence as same as in enhancer sequence located 185bp downstream inside second intron[8] may suggesting negative regulation of transcription by exogenous stimulation like microbial metabolites in the gut.
Function
The main function of membrane-bound CD83 is stabilization of MHC II., costimulatory molecules and CD28 in membrane by its transmembrane domain antagonistic activity to MARCH family E3 ubiquitin ligases[9][10].
Ligands
It is not clear what ligands interact with CD83 but it looks like that membrane-bound CD83 homotypicaly interacts with soluble form may suggest autocrine immune regulation. However, it contrasts with differences between the single expression of soluble CD83 on monocytes and membrane CD83 on activated DCs. Soluble CD83 also binds to CD153 leading to supports Th2 T lymphocytes apoptosis by suppression of BCL inhibitors.
Positive selection
It was suggested that the thymocytes during positive selection could be aimed by CD83 expression on cortical thymic epithelial cells (cTECs). Double positive (DP) thymocytes inside specially differentiated cTECs called thymic nurse cells (TNCs) are tested to function of their αβTCR, where nonreactive TCR leads to thymocyte death by neglect. Successful rearrangement of reactive TCR supports surviving and conservation of just CD4 or CD8 expression on single positive (SP) thymocytes caused by recognition ability of MHC II. or MHC I. CD83 upregulates turnover of MHC II. on TNCs may enlarges population of CD4 SP thymocytes [11][12].
Regulatory T cells
T regulatory cells are present in two major populations as thymic induced and peripherialy induced Tregs. All Tregs express Foxp3 transcription factor estabilishs their suppressive phenotype. Foxp3 expression is not affected by CD83 in CD83 KO mouse. In contrast CD83 seems important for peripheral Tregs induction suggests by reduction of this population in CD83 KO showing proinflammatory phenotype. CD83 deficiency also shows disbalances in effectory function of Tregs as decreased expression of Th2 transcription factor GATA3 also important for ST2 production. Activated Tregs masively produce soluble CD83 leading to downregulation of IRAK-1 in infammed sites leading to TLR signalization down-regulation and switch inflammatory signals to tolerance establishment.
Dendritic cells
As said previously, CD83 stabilizes MHC II. on membrane by antagonistic activity of CD83 on MARCH E3 ubiquitin ligases. MARCH1 KO mouse revealeds accumulation of MHC II. on membrane causes reduced CD4+ T lymphocytes activation together with IL-12 production. On the other hand, CD83 KO with reduction of MHC II. and CD86 shows better response to bacterial infection and high production of IL-12 contrasting with WT mouse. CD83 seems to be important regulator of DCs phenotypes and MHC II. turnover by CD83 dependent endosome processing
B cells
CD83 expression correlates with rate of activation of B lymphocytes and it is under control of BCR, CD40, or TLRs activation similarly to other lymphocytes, where CD83 is expressed just after stimulation. CD83 KO shows up-regulated proliferation of B lymphocytes, suggesting that CD83 plays a role as a proliferation activated brake. CD83 does not affect affine maturation of antibodies, but its deficiency supports IgE class switch, suggesting importance of CD83 in allergy development and utilize it as therapeutic target in allergy treatment.
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000112149 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000015396 – 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.
- ^ "Entrez Gene: CD83 CD83 molecule".
- ^ Berchtold S, Jones T, Mühl-Zürbes P, Sheer D, Schuler G, Steinkasserer A (March 1999). "The human dendritic cell marker CD83 maps to chromosome 6p23". Annals of Human Genetics. 63 (Pt 2): 181–3. doi:10.1046/j.1469-1809.1999.6320181.x. PMID 10738529.
- ^ Stein MF, Lang S, Winkler TH, Deinzer A, Erber S, Nettelbeck DM, et al. (April 2013). "Multiple interferon regulatory factor and NF-κB sites cooperate in mediating cell-type- and maturation-specific activation of the human CD83 promoter in dendritic cells". Molecular and Cellular Biology. 33 (7): 1331–44. doi:10.1128/MCB.01051-12. PMID 23339870.
- ^ Michalski J, Deinzer A, Stich L, Zinser E, Steinkasserer A, Knippertz I (July 2020). "Quercetin induces an immunoregulatory phenotype in maturing human dendritic cells". Immunobiology. 225 (4): 151929. doi:10.1016/j.imbio.2020.151929. PMID 32115260.
- ^ Grosche, Linda; Knippertz, Ilka; König, Christina; Royzman, Dmytro; Wild, Andreas B.; Zinser, Elisabeth; Sticht, Heinrich; Muller, Yves A.; Steinkasserer, Alexander; Lechmann, Matthias (17 April 2020). "The CD83 Molecule – An Important Immune Checkpoint". Frontiers in Immunology. 11: 721. doi:10.3389/fimmu.2020.00721.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ von Rohrscheidt, Julia; Petrozziello, Elisabetta; Nedjic, Jelena; Federle, Christine; Krzyzak, Lena; Ploegh, Hidde L.; Ishido, Satoshi; Steinkasserer, Alexander; Klein, Ludger (22 August 2016). "Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83". Journal of Experimental Medicine. 213 (9): 1685–1694. doi:10.1084/jem.20160316.
- ^ Kadouri, Noam; Nevo, Shir; Goldfarb, Yael; Abramson, Jakub (April 2020). "Thymic epithelial cell heterogeneity: TEC by TEC". Nature Reviews Immunology. 20 (4): 239–253. doi:10.1038/s41577-019-0238-0.
- ^ von Rohrscheidt, Julia; Petrozziello, Elisabetta; Nedjic, Jelena; Federle, Christine; Krzyzak, Lena; Ploegh, Hidde L.; Ishido, Satoshi; Steinkasserer, Alexander; Klein, Ludger (22 August 2016). "Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83". Journal of Experimental Medicine. 213 (9): 1685–1694. doi:10.1084/jem.20160316.
Further reading
- Lechmann M, Berchtold S, Hauber J, Steinkasserer A (June 2002). "CD83 on dendritic cells: more than just a marker for maturation". Trends in Immunology. 23 (6): 273–5. doi:10.1016/S1471-4906(02)02214-7. PMID 12072358.
- Zhou LJ, Schwarting R, Smith HM, Tedder TF (July 1992). "A novel cell-surface molecule expressed by human interdigitating reticulum cells, Langerhans cells, and activated lymphocytes is a new member of the Ig superfamily". Journal of Immunology. 149 (2): 735–42. PMID 1378080.
- Zhou LJ, Tedder TF (April 1995). "Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily". Journal of Immunology. 154 (8): 3821–35. PMID 7706722.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Kozlow EJ, Wilson GL, Fox CH, Kehrl JH (January 1993). "Subtractive cDNA cloning of a novel member of the Ig gene superfamily expressed at high levels in activated B lymphocytes". Blood. 81 (2): 454–61. doi:10.1182/blood.V81.2.454.454. PMID 8422464.
- de la Fuente MA, Pizcueta P, Nadal M, Bosch J, Engel P (September 1997). "CD84 leukocyte antigen is a new member of the Ig superfamily". Blood. 90 (6): 2398–405. doi:10.1182/blood.V90.6.2398. PMID 9310491.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Olavesen MG, Bentley E, Mason RV, Stephens RJ, Ragoussis J (December 1997). "Fine mapping of 39 ESTs on human chromosome 6p23-p25". Genomics. 46 (2): 303–6. doi:10.1006/geno.1997.5032. PMID 9417921.
- Twist CJ, Beier DR, Disteche CM, Edelhoff S, Tedder TF (1998). "The mouse Cd83 gene: structure, domain organization, and chromosome localization". Immunogenetics. 48 (6): 383–93. doi:10.1007/s002510050449. PMID 9799334. S2CID 19869850.
- Berchtold S, Mühl-Zürbes P, Heufler C, Winklehner P, Schuler G, Steinkasserer A (November 1999). "Cloning, recombinant expression and biochemical characterization of the murine CD83 molecule which is specifically upregulated during dendritic cell maturation". FEBS Letters. 461 (3): 211–6. doi:10.1016/S0014-5793(99)01465-9. PMID 10567699. S2CID 28053654.
- Scholler N, Hayden-Ledbetter M, Hellström KE, Hellström I, Ledbetter JA (March 2001). "CD83 is an I-type lectin adhesion receptor that binds monocytes and a subset of activated CD8+ T cells [corrected]". Journal of Immunology. 166 (6): 3865–72. doi:10.4049/jimmunol.166.6.3865. PMID 11238630.
- Fanales-Belasio E, Moretti S, Nappi F, Barillari G, Micheletti F, Cafaro A, Ensoli B (January 2002). "Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses". Journal of Immunology. 168 (1): 197–206. doi:10.4049/jimmunol.168.1.197. PMID 11751963. S2CID 25473321.
- Berchtold S, Mühl-Zürbes P, Maczek E, Golka A, Schuler G, Steinkasserer A (July 2002). "Cloning and characterization of the promoter region of the human CD83 gene". Immunobiology. 205 (3): 231–46. doi:10.1078/0171-2985-00128. PMID 12182451.
- te Velde AA, van Kooyk Y, Braat H, Hommes DW, Dellemijn TA, Slors JF, et al. (January 2003). "Increased expression of DC-SIGN+IL-12+IL-18+ and CD83+IL-12-IL-18- dendritic cell populations in the colonic mucosa of patients with Crohn's disease". European Journal of Immunology. 33 (1): 143–51. doi:10.1002/immu.200390017. PMID 12594843. S2CID 44959575.
- Dudziak D, Kieser A, Dirmeier U, Nimmerjahn F, Berchtold S, Steinkasserer A, et al. (August 2003). "Latent membrane protein 1 of Epstein-Barr virus induces CD83 by the NF-kappaB signaling pathway". Journal of Virology. 77 (15): 8290–8. doi:10.1128/JVI.77.15.8290-8298.2003. PMC 165234. PMID 12857898.
- Hock BD, Haring LF, Steinkasserer A, Taylor KG, Patton WN, McKenzie JL (March 2004). "The soluble form of CD83 is present at elevated levels in a number of hematological malignancies". Leukemia Research. 28 (3): 237–41. doi:10.1016/S0145-2126(03)00255-8. PMID 14687618.
- Sénéchal B, Boruchov AM, Reagan JL, Hart DN, Young JW (June 2004). "Infection of mature monocyte-derived dendritic cells with human cytomegalovirus inhibits stimulation of T-cell proliferation via the release of soluble CD83". Blood. 103 (11): 4207–15. doi:10.1182/blood-2003-12-4350. PMID 14962896.
- Cao W, Lee SH, Lu J (January 2005). "CD83 is preformed inside monocytes, macrophages and dendritic cells, but it is only stably expressed on activated dendritic cells". The Biochemical Journal. 385 (Pt 1): 85–93. doi:10.1042/BJ20040741. PMC 1134676. PMID 15320871.
External links
- CD83+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CD83 genome location and CD83 gene details page in the UCSC Genome Browser.
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