Biology:CD58

From HandWiki
Short description: Mammalian protein found in Homo sapiens
CD58 molecule
Identifiers
SymbolCD58
Alt. symbolsLFA3
NCBI gene965
HGNC1688
OMIM153420
RefSeqNM_001779
UniProtP19256
Other data
LocusChr. 1 p13

CD58, or lymphocyte function-associated antigen 3 (LFA-3), is a cell adhesion molecule expressed on Antigen Presenting Cells (APCs), particularly macrophages, and other tissue cells.[1][2][3]

CD58 binds to CD2 (LFA-2) [4][5] on T cells and is important in strengthening the adhesion and recognition between the T cells and Professional Antigen Presenting Cells, facilitating signal transduction necessary for an immune response. This adhesion occurs as part of the transitory initial encounters between T cells and Antigen Presenting Cells before T cell activation, when T cells are roaming the lymph nodes looking at the surface of APCs for peptide:MHC complexes the T-cell receptors are reactive to.

Polymorphisms in the CD58 gene are associated with increased risk for multiple sclerosis.[6] Genomic region containing the single-nucleotide polymorphism rs1335532, associated with high risk of multiple sclerosis, has enhancer properties and can significantly boost the CD58 promoter activity in lymphoblast cells. The protective (C) rs1335532 allele creates functional binding site for ASCL2 transcription factor, a target of the Wnt signaling pathway.[7]

CD58 plays a role in the regulation of colorectal tumor-initiating cells (CT-ICs). Thus, cells that express CD58 have become a cell of interest in tumorigenesis.[8] Mutations of CD58 have been linked to immune evasion observed in some lymphomas and studies are underway to analyze how its involvement directly affects classical Hodgkin lymphoma (cHL).[9]

Introduction

CD58, lymphocyte-function antigen 3 (LFA-3), is a glycoprotein that plays a vital role in the body's immune response. The natural ligand to CD58, CD2, is most commonly found on the surfaces of both T cells and Natural Killer cells (T/NK cells).[3] During an immune response, the interactions between the CD2 and CD58 glycoproteins allows for the activation and proliferation of both T and Natural Killer cells (T/NK cells), enhancing cell adhesion.[3] Furthermore, upon activation, a succession of intracellular signaling within T and Natural Killer cells and other target cells occurs, enhancing further cell recognition.[3] Overall, CD58-CD2 interactions are intricate and involved in a variety of immune regulatory responses, including antiviral, inflammation in numerous autoimmune diseases, and immune rejections in organ transplants.[3]

CD58 is expressed on a variety of different cells, including hematopoietic and nonhematopoietic cells.[10] More specifically, CD58 is expressed on cell surfaces, allowing for effector-target adhesion sequentially to antigen recognition.[11] This adhesion allows for proper T cell activation via correct cell signaling.

CD58 and CD2 interaction

The composition of CD2 and CD58 share many similarities. Both extracellular domains have similar amino acid sequences which aid in cell adhesion.[12] This allows for a high affinity of the extracellular amino-terminal sequence on CD2 to bind with CD58, which has a capacity to bind to CD2 on T cells, on target cells.[12][13] For a regulatory T cell to become activated, the recognition of an antigen located within a major histocompatibility complex (MHC) protein by the TcR, or T cell receptor, is insufficient.[14] Proliferation of regulatory T cells requires the TcR recognition and other co-stimulatory signals.[15] The binding of CD2-CD58 allows for the formation of a co-stimulatory signal, contributing to further regulatory T cell proliferation and regulation of T cell responses via signaling transduction.[15][16]

Structure and localization of CD58

The CD58 glycoprotein can be found in two different protein isoforms, each on the cell surface.[17] These include transmembrane and GPI-anchored form.[17] It has been found that in both isoforms, CD58 is able to interact with a variety of different kinases, and is not dependent on only one form.[17] Rather, each isoform is able to associate more effectively with different kinases.[18] Each form, transmembrane and GPI-anchored, can be found in different parts of the cell membrane. The GPI-anchored isoform is mostly found in lipid rafts while the transmembrane isoform is mainly found in nonraft domains.[18] Despite this, the transmembrane CD58 form can trigger independent signaling without the need for the GPI-anchored isoform.[18] Transmembrane CD58 has a structure that consists of six N-linked glycosylation sites in the extracellular domain, a hydrophobic transmembrane domain, and finally a short cytoplasmic domain.[19] GPI-anchored CD58 has a similar extracellular domain, but no hydrophobic transmembrane domain or cytoplasmic domain.[19] Rather, it is linked to the cell membrane via a GPI tail. It is estimated that the CD58 structure is made of approximately 44-68% carbohydrate.[19] The structure of CD58 also plays a role in cell adhesion. A study found that effective cell adhesion was dependent on the density of CD58.[20] Comparing the GPI-anchored and transmembrane isoforms, the GPI-anchored is much more efficient during cell adhesion, and on average, takes much less time than the transmembrane isoform.[20] Regardless, the structure of both the GPI-anchor and transmembrane CD58 are crucial in overall function. While the GPI-anchor enhances cell adhesion, the transmembrane isoform is more efficient in cell signal transduction.[3]

Multiple sclerosis

Multiple Sclerosis (MS) is autoimmune disease that effects the central nervous system (CNS). In an individual with MS, the immune system attacks the myelin sheath, which are crucial for covering nerve fibers and allowing proper communication with the brain and the rest of the body.[21] A genomic association study suggested that there is a risk of developing MS in individuals with allelic variation in the CD58 gene coding region.[22] Further research done on the topic suggested that there is a strong association betweenCD58 single-nucleotide polymorphism (SNP) rs12044852 and the onset of MS.[23] Another study focused on the (SNP) rs1414273 in the microRNA-548ac stem-loop region of the CD58 gene.[24] More specifically, the SNP was found to have an influence on Drosha cleavage activity, which can cause uncoupling of the expression of CD58 and microRNA-548ac production.[24] The data from the study also showed carriers of the allele rs1414273 showed an overall decrease in CD58 mRNA levels.[24] However, the carriers of the allele did exhibit an increase in the levels of hsa-miR-548ac.[24] There is an influence between CD58 and susceptibility to MS. On a similar note, a genome wide association study found that the SNP rs1335532 was associated with a decrease in the susceptibility of developing MS.[25] In addition, it was found that in individuals with MS had an increase in CD58 mRNA.[25] This was because the region where rs1335532 resides had certain properties that increased the activity of CD58 in lymphoblasts.[25] The protective rs1335532 allele also targeted the Wnt signaling pathway by creating a binding site for ASCL2, a transcription factor and target of the Wnt signaling pathway.[25] In immune cells like monocytes and primary B-cells, the Wnt signaling pathway activation causes an increase in CD58 promotor activity via a strong binding site of ASCL2.[25] A reduced expression of CD58 is a possible risk for developing MS.

Rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that mainly affects an individual's joints, but can affect and cause problems in different tissues.[26] A study that used enzyme-linked immunosorbent assay (ELISA) to measure sCD58 (soluble form of CD58) in individuals with RA and normal controls (NC) to determine if there was a correlation between sCD58 levels and RA.[27] It was found that sCD58 levels were significantly lower in the individuals with RA compared to those in the control (NC).[27] The sCD58 levels in the synovial fluid (SF) of the individuals with RA were also lower than the control subjects.[27] A decrease in sCD58 production could cause a decrease in CD2-CD58 adhesion, leading to an increase in T cells.[28] Continued inflammation would also be an effect of the decrease in sCD58.[28]

References

  1. ↑ "Gene mapping and somatic cell hybrid analysis of the role of human lymphocyte function-associated antigen-3 (LFA-3) in CTL-target cell interactions". Journal of Immunology 136 (8): 3085–91. April 1986. doi:10.4049/jimmunol.136.8.3085. PMID 3514752. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=3514752. 
  2. ↑ "Gene structure, promoter characterization, and basis for alternative mRNA splicing of the human CD58 gene". Journal of Immunology 160 (6): 2862–71. March 1998. doi:10.4049/jimmunol.160.6.2862. PMID 9510189. http://www.jimmunol.org/cgi/content/abstract/160/6/2862. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Zhang, Yalu; Liu, Qiaofei; Yang, Sen; Liao, Quan (2021-06-08). "CD58 Immunobiology at a Glance". Frontiers in Immunology 12: 705260. doi:10.3389/fimmu.2021.705260. ISSN 1664-3224. PMID 34168659. 
  4. ↑ "The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3". Nature 326 (6111): 400–3. 1987. doi:10.1038/326400a0. PMID 2951597. Bibcode: 1987Natur.326..400S. 
  5. ↑ "Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors". Cell 97 (6): 791–803. June 1999. doi:10.1016/S0092-8674(00)80790-4. PMID 10380930. 
  6. ↑ "The role of the CD58 locus in multiple sclerosis". Proceedings of the National Academy of Sciences of the United States of America 106 (13): 5264–9. March 2009. doi:10.1073/pnas.0813310106. PMID 19237575. Bibcode: 2009PNAS..106.5264D. 
  7. ↑ "Protective C allele of the single-nucleotide polymorphism rs1335532 is associated with strong binding of Ascl2 transcription factor and elevated CD58 expression in B-cells". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864 (10): 3211–3220. October 2018. doi:10.1016/j.bbadis.2018.07.008. PMID 30006149. 
  8. ↑ "CD58, a novel surface marker, promotes self-renewal of tumor-initiating cells in colorectal cancer". Oncogene 34 (12): 1520–31. March 2015. doi:10.1038/onc.2014.95. PMID 24727892. 
  9. ↑ "Alterations of the CD58 gene in classical Hodgkin lymphoma". Genes, Chromosomes & Cancer 54 (10): 638–45. October 2015. doi:10.1002/gcc.22276. PMID 26194173. 
  10. ↑ Krensky, A. M.; Sanchez-Madrid, F.; Robbins, E.; Nagy, J. A.; Springer, T. A.; Burakoff, S. J. (August 1983). "The functional significance, distribution, and structure of LFA-1, LFA-2, and LFA-3: cell surface antigens associated with CTL-target interactions". Journal of Immunology 131 (2): 611–616. doi:10.4049/jimmunol.131.2.611. ISSN 0022-1767. PMID 6345670. 
  11. ↑ Krensky, A. M.; Robbins, E.; Springer, T. A.; Burakoff, S. J. (May 1984). "LFA-1, LFA-2, and LFA-3 antigens are involved in CTL-target conjugation". Journal of Immunology 132 (5): 2180–2182. doi:10.4049/jimmunol.132.5.2180. ISSN 0022-1767. PMID 6201533. https://pubmed.ncbi.nlm.nih.gov/6201533/. 
  12. ↑ 12.0 12.1 Sewell, W. A.; Palmer, R. W.; Spurr, N. K.; Sheer, D.; Brown, M. H.; Bell, Y.; Crumpton, M. J. (1988). "The human LFA-3 gene is located at the same chromosome band as the gene for its receptor CD2". Immunogenetics 28 (4): 278–282. doi:10.1007/BF00345506. ISSN 0093-7711. PMID 2458315. https://pubmed.ncbi.nlm.nih.gov/2458315/. 
  13. ↑ Selvaraj, P.; Plunkett, M. L.; Dustin, M.; Sanders, M. E.; Shaw, S.; Springer, T. A. (March 26 – April 1, 1987). "The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3". Nature 326 (6111): 400–403. doi:10.1038/326400a0. ISSN 0028-0836. PMID 2951597. Bibcode: 1987Natur.326..400S. https://pubmed.ncbi.nlm.nih.gov/2951597/. 
  14. ↑ Bierer, B. E.; Hahn, W. C. (August 1993). "T cell adhesion, avidity regulation and signaling: a molecular analysis of CD2". Seminars in Immunology 5 (4): 249–261. doi:10.1006/smim.1993.1029. ISSN 1044-5323. PMID 7693022. https://pubmed.ncbi.nlm.nih.gov/7693022/. 
  15. ↑ 15.0 15.1 Van Seventer, G. A.; Shimizu, Y.; Horgan, K. J.; Luce, G. E.; Webb, D.; Shaw, S. (July 1991). "Remote T cell co-stimulation via LFA-1/ICAM-1 and CD2/LFA-3: demonstration with immobilized ligand/mAb and implication in monocyte-mediated co-stimulation". European Journal of Immunology 21 (7): 1711–1718. doi:10.1002/eji.1830210719. ISSN 0014-2980. PMID 1711977. https://pubmed.ncbi.nlm.nih.gov/1711977/. 
  16. ↑ Miller, G. T.; Hochman, P. S.; Meier, W.; Tizard, R.; Bixler, S. A.; Rosa, M. D.; Wallner, B. P. (1993-07-01). "Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses". The Journal of Experimental Medicine 178 (1): 211–222. doi:10.1084/jem.178.1.211. ISSN 0022-1007. PMID 7686212. 
  17. ↑ 17.0 17.1 17.2 Itzhaky, D.; Raz, N.; Hollander, N. (1998-05-01). "The glycosylphosphatidylinositol-anchored form and the transmembrane form of CD58 associate with protein kinases". Journal of Immunology 160 (9): 4361–4366. doi:10.4049/jimmunol.160.9.4361. ISSN 0022-1767. PMID 9574540. 
  18. ↑ 18.0 18.1 18.2 Ariel, Ortal; Kukulansky, Tova; Raz, Nava; Hollander, Nurit (June 2004). "Distinct membrane localization and kinase association of the two isoforms of CD58". Cellular Signalling 16 (6): 667–673. doi:10.1016/j.cellsig.2003.08.015. ISSN 0898-6568. PMID 15093607. https://pubmed.ncbi.nlm.nih.gov/15093607/. 
  19. ↑ 19.0 19.1 19.2 Wallner, B. P.; Frey, A. Z.; Tizard, R.; Mattaliano, R. J.; Hession, C.; Sanders, M. E.; Dustin, M. L.; Springer, T. A. (1987-10-01). "Primary structure of lymphocyte function-associated antigen 3 (LFA-3). The ligand of the T lymphocyte CD2 glycoprotein". The Journal of Experimental Medicine 166 (4): 923–932. doi:10.1084/jem.166.4.923. ISSN 0022-1007. PMID 3309127. 
  20. ↑ 20.0 20.1 Chan, P. Y.; Lawrence, M. B.; Dustin, M. L.; Ferguson, L. M.; Golan, D. E.; Springer, T. A. (October 1991). "Influence of receptor lateral mobility on adhesion strengthening between membranes containing LFA-3 and CD2". The Journal of Cell Biology 115 (1): 245–255. doi:10.1083/jcb.115.1.245. ISSN 0021-9525. PMID 1717480. 
  21. ↑ "Multiple sclerosis - Symptoms and causes" (in en). https://www.mayoclinic.org/diseases-conditions/multiple-sclerosis/symptoms-causes/syc-20350269. 
  22. ↑ De Jager, Philip L.; Baecher-Allan, Clare; Maier, Lisa M.; Arthur, Ariel T.; Ottoboni, Linda; Barcellos, Lisa; McCauley, Jacob L.; Sawcer, Stephen et al. (2009-03-31). "The role of the CD58 locus in multiple sclerosis". Proceedings of the National Academy of Sciences of the United States of America 106 (13): 5264–5269. doi:10.1073/pnas.0813310106. ISSN 1091-6490. PMID 19237575. Bibcode: 2009PNAS..106.5264D. 
  23. ↑ Torbati, Sara; Karami, Fatemeh; Ghaffarpour, Majid; Zamani, Mahdi (2015). "Association of CD58 Polymorphism with Multiple Sclerosis and Response to Interferon ß Therapy in A Subset of Iranian Population". Cell Journal 16 (4): 506–513. doi:10.22074/cellj.2015.505. ISSN 2228-5806. PMID 25685741. 
  24. ↑ 24.0 24.1 24.2 24.3 Hecker, Michael; Boxberger, Nina; Illner, Nicole; Fitzner, Brit; Schröder, Ina; Winkelmann, Alexander; Dudesek, Ales; Meister, Stefanie et al. (February 2019). "A genetic variant associated with multiple sclerosis inversely affects the expression of CD58 and microRNA-548ac from the same gene". PLOS Genetics 15 (2): e1007961. doi:10.1371/journal.pgen.1007961. ISSN 1553-7404. PMID 30730892. 
  25. ↑ 25.0 25.1 25.2 25.3 25.4 Mitkin, Nikita A.; Muratova, Alisa M.; Korneev, Kirill V.; Pavshintsev, Vsevolod V.; Rumyantsev, Konstantin A.; Vagida, Murad S.; Uvarova, Aksinya N.; Afanasyeva, Marina A. et al. (October 2018). "Protective C allele of the single-nucleotide polymorphism rs1335532 is associated with strong binding of Ascl2 transcription factor and elevated CD58 expression in B-cells". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864 (10): 3211–3220. doi:10.1016/j.bbadis.2018.07.008. ISSN 1879-260X. PMID 30006149. https://pubmed.ncbi.nlm.nih.gov/30006149/. 
  26. ↑ "Rheumatoid Arthritis (RA) | Arthritis | CDC" (in en-us). 2020-07-27. https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html. 
  27. ↑ 27.0 27.1 27.2 Hoffmann, J. C.; Räuker, H. J.; Krüger, H.; Bayer, B.; Zeidler, H. (1996). "Decreased levels of a soluble form of the human adhesion receptor CD58 (LFA-3) in sera and synovial fluids of patients with rheumatoid arthritis". Clinical and Experimental Rheumatology 14 (1): 23–29. ISSN 0392-856X. PMID 8697653. https://pubmed.ncbi.nlm.nih.gov/8697653/. 
  28. ↑ 28.0 28.1 Hoffmann, J. C.; Bayer, B.; Zeidler, H. (June 1996). "Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA)". Clinical and Experimental Immunology 104 (3): 460–466. doi:10.1046/j.1365-2249.1996.41749.x. ISSN 0009-9104. PMID 9099931. 

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