CD58

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

CD58 molecule
Identifiers
SymbolCD58
Alt. symbolsLFA3
NCBI gene965
HGNC1688
OMIM153420
RefSeqNM_001779
UniProtP19256
Other data
LocusChr. 1 p13

It binds to CD2 (LFA-2) [3][4] on T cells and is important in strengthening the adhesion between the T cells and Professional Antigen Presenting Cells. 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.[5] 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 [6]

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.[7] 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).[8]


References
  1. Barbosa JA, Mentzer SJ, Kamarck ME, Hart J, Biro PA, Strominger JL, Burakoff SJ (April 1986). "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. PMID 3514752.
  2. Wallich R, Brenner C, Brand Y, Roux M, Reister M, Meuer S (March 1998). "Gene structure, promoter characterization, and basis for alternative mRNA splicing of the human CD58 gene". Journal of Immunology. 160 (6): 2862–71. PMID 9510189.
  3. Selvaraj P, Plunkett ML, Dustin M, Sanders ME, Shaw S, Springer TA (1987). "The T lymphocyte glycoprotein CD2 binds the cell surface ligand LFA-3". Nature. 326 (6111): 400–3. Bibcode:1987Natur.326..400S. doi:10.1038/326400a0. PMID 2951597.
  4. Wang JH, Smolyar A, Tan K, Liu JH, Kim M, Sun ZY, et al. (June 1999). "Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors". Cell. 97 (6): 791–803. doi:10.1016/S0092-8674(00)80790-4. PMID 10380930.
  5. De Jager PL, Baecher-Allan C, Maier LM, Arthur AT, Ottoboni L, Barcellos L, et al. (March 2009). "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. Bibcode:2009PNAS..106.5264D. doi:10.1073/pnas.0813310106. PMC 2664005. PMID 19237575.
  6. Mitkin NA, Muratova AM, Korneev KV, Pavshintsev VV, Rumyantsev KA, Vagida MS, 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. PMID 30006149.
  7. Xu S, Wen Z, Jiang Q, Zhu L, Feng S, Zhao Y, et al. (March 2015). "CD58, a novel surface marker, promotes self-renewal of tumor-initiating cells in colorectal cancer". Oncogene. 34 (12): 1520–31. doi:10.1038/onc.2014.95. PMID 24727892.
  8. Schneider M, Schneider S, Zühlke-Jenisch R, Klapper W, Sundström C, Hartmann S, et al. (October 2015). "Alterations of the CD58 gene in classical Hodgkin lymphoma". Genes, Chromosomes & Cancer. 54 (10): 638–45. doi:10.1002/gcc.22276. PMID 26194173.
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