CD48

CD48
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCD48, BCM1, BLAST, BLAST1, MEM-102, SLAMF2, hmCD48 molecule
External IDsMGI: 88339 HomoloGene: 1347 GeneCards: CD48
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1q23.3Start160,678,746 bp[1]
End160,711,851 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

962

12506

Ensembl

ENSG00000117091

ENSMUSG00000015355

UniProt

P09326

P18181

RefSeq (mRNA)

NM_001256030
NM_001778

NM_007649
NM_001360767

RefSeq (protein)

NP_001242959
NP_001769

NP_031675
NP_001347696

Location (UCSC)Chr 1: 160.68 – 160.71 MbChr 1: 171.68 – 171.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

CD48 antigen (Cluster of Differentiation 48) also known as B-lymphocyte activation marker (BLAST-1) or signaling lymphocytic activation molecule 2 (SLAMF2) is a protein that in humans is encoded by the CD48 gene.[5]

CD48 is a member of the CD2 subfamily of the immunoglobulin superfamily (IgSF) which includes SLAM (signaling lymphocyte activation molecules) proteins, such as CD84, CD150, CD229 and CD244. CD48 is found on the surface of lymphocytes and other immune cells, dendritic cells and endothelial cells, and participates in activation and differentiation pathways in these cells.[5]

CD48 was the first B-cell-specific cellular differentiation antigen identified in transformed B lymphoblasts.[6][7]

Structure

The gene for CD48 is located in chromosome 1q23 and contains 4 exons, each exon encoding one of the 4 domains of CD48: signal peptide, variable (V) domain, constant 2 (C2) domain and the glycophosphatidylinositol anchor (GPI anchor). The cDNA sequence of 1137 nucleotides encodes a 243 amino acid polypeptide of about 45 kDa.[8][9] It consists of a 26 amino acid signal peptide, 194 amino acids of mature CD48 (V and C2 domains) and the C-terminal 23 amino acid segment comprising the GPI anchor.[10][11] The GPI linkage of CD48 to the cell surface is through serine residue 220.[10][11] CD48 does not have a transmembrane domain, however, but is held at the cell surface by a GPI anchor via a C-terminal domain which can be cleaved to yield a soluble form of the receptor.[5] The CD48 protein is heavily glycosylated, with five possible asparagine-linked glycosylation sites at positions 40, 44, 104, 162 and 189, respectively.[6][7][8][12][13] Approximately 35-40% of the total molecular weight is attributed to the carbohydrate side chains.[12][13][14]

Interactions

CD48 was found to have a very low affinity for CD2 with dissociation constant ( ) < 0.5 mM.[15] It was found that the preferred ligand of CD48 is 2B4 (CD244), which is also a member of the CD2 subfamily SLAM of IgSF expressed on natural killer cells (NK cells) and other leukocytes. The affinity of CD244 for CD48 is at = 8 μM which is about 5 - 10 times stronger than for CD2.[16][17][18]

Function

Cell distribution

CD48 is expressed on all peripheral blood lymphocytes (PBL) including T cells, B cells, NK cells and thymocytes.[7][8][14][19] It is also found on the surface of activated T cells, mast cells, monocytes and granulocytes.[12] Like all other GPI anchor protein (GPI-AP), CD48 is deficient in erythrocytes (red blood cells).

T cell activation

CD48 and CD2 molecular coupling together with other interaction pairs of CD28 and CD80, TCR and peptide-MHC and LFA-1 and ICAM-1 contribute to the formation of an immunological synapse between a T cell and an antigen presenting cell.[20] CD48 interaction with CD2 has been shown to promote lipid raft formation, T cell activation and the formation of caveolae for macrophages through cell signal transductionthe via GPI moieties.[21][22]

Clinical Significance

CD48 is being investigated amongst other markers in research on inflammation markers and therapies for HIV/AIDS.

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000117091 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015355 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. 1 2 3 "Entrez Gene: CD48 CD48 molecule".
  6. 1 2 Thorley-Lawson DA, Schooley RT, Bhan AK, Nadler LM (September 1982). "Epstein-Barr virus superinduces a new human B cell differentiation antigen (B-LAST 1) expressed on transformed lymphoblasts". Cell. 30 (2): 415–25. doi:10.1016/0092-8674(82)90239-2. PMID 6291768.
  7. 1 2 3 Yokoyama S, Staunton D, Fisher R, Amiot M, Fortin JJ, Thorley-Lawson DA (April 1991). "Expression of the Blast-1 activation/adhesion molecule and its identification as CD48". J. Immunol. 146 (7): 2192–200. PMID 1848579.
  8. 1 2 3 Vaughan HA, Henning MM, Purcell DF, McKenzie IF, Sandrin MS (1991). "The isolation of cDNA clones for CD48". Immunogenetics. 33 (2): 113–7. doi:10.1007/BF00210824. PMID 1999351.
  9. ↑ Del Porto P, Mami-Chouaib F, Bruneau JM, Jitsukawa S, Dumas J, Harnois M, Hercend T (June 1991). "TCT.1, a target molecule for gamma/delta T cells, is encoded by an immunoglobulin superfamily gene (Blast-1) located in the CD1 region of human chromosome 1". J. Exp. Med. 173 (6): 1339–44. doi:10.1084/jem.173.6.1339. PMC 2190850. PMID 1827826.
  10. 1 2 Killeen N, Moessner R, Arvieux J, Willis A, Williams AF (October 1988). "The MRC OX-45 antigen of rat leukocytes and endothelium is in a subset of the immunoglobulin superfamily with CD2, LFA-3 and carcinoembryonic antigens". EMBO J. 7 (10): 3087–91. PMC 454697. PMID 3181129.
  11. 1 2 Staunton DE, Fisher RC, LeBeau MM, Lawrence JB, Barton DE, Francke U, Dustin M, Thorley-Lawson DA (March 1989). "Blast-1 possesses a glycosyl-phosphatidylinositol (GPI) membrane anchor, is related to LFA-3 and OX-45, and maps to chromosome 1q21-23". J. Exp. Med. 169 (3): 1087–99. doi:10.1084/jem.169.3.1087. PMC 2189294. PMID 2466936.
  12. 1 2 3 Staunton DE, Thorley-Lawson DA (December 1987). "Molecular cloning of the lymphocyte activation marker Blast-1". EMBO J. 6 (12): 3695–701. PMC 553839. PMID 2828034.
  13. 1 2 Rudd PM, Wormald MR, Stanfield RL, Huang M, Mattsson N, Speir JA, DiGennaro JA, Fetrow JS, Dwek RA, Wilson IA (October 1999). "Roles for glycosylation of cell surface receptors involved in cellular immune recognition". J. Mol. Biol. 293 (2): 351–66. doi:10.1006/jmbi.1999.3104. PMID 10529350.
  14. 1 2 Vaughan HA, Thompson CH, Sparrow RL, McKenzie IF (October 1983). "Hu Ly-M3--a human leukocyte antigen". Transplantation. 36 (4): 446–50. doi:10.1097/00007890-198310000-00018. PMID 6623618.
  15. ↑ Sandrin MS, Mouhtouris E, Vaughan HA, Warren HS, Parish CR (November 1993). "CD48 is a low affinity ligand for human CD2". J. Immunol. 151 (9): 4606–13. PMID 7691954.
  16. ↑ Brown MH, Boles K, van der Merwe PA, Kumar V, Mathew PA, Barclay AN (December 1998). "2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48". J. Exp. Med. 188 (11): 2083–90. doi:10.1084/jem.188.11.2083. PMC 2212392. PMID 9841922.
  17. ↑ Kubin MZ, Parshley DL, Din W, Waugh JY, Davis-Smith T, Smith CA, Macduff BM, Armitage RJ, Chin W, Cassiano L, Borges L, Petersen M, Trinchieri G, Goodwin RG (November 1999). "Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48". Eur. J. Immunol. 29 (11): 3466–77. doi:10.1002/(SICI)1521-4141(199911)29:11<3466::AID-IMMU3466>3.0.CO;2-9. PMID 10556801.
  18. ↑ Nakajima H, Colonna M (January 2000). "2B4: an NK cell activating receptor with unique specificity and signal transduction mechanism". Hum. Immunol. 61 (1): 39–43. doi:10.1016/s0198-8859(99)00170-6. PMID 10658976.
  19. ↑ Henniker AJ, Bradstock KF, Grimsley P, Atkinson MK (1990). "A novel non-lineage antigen on human leucocytes: characterization with two CD-48 monoclonal antibodies". Dis. Markers. 8 (4): 179–90. PMID 2088634.
  20. ↑ Malissen B (1999). "Dancing the immunological two-step". Science. 285 (5425): 207–208. doi:10.1126/science.285.5425.207. PMID 10428718.
  21. ↑ Mulvey MA, Hultgren SJ (2000). "Cell biology. Bacterial spelunkers". Science. 289 (5480): 732–733. doi:10.1126/science.289.5480.732. PMID 10950716.
  22. ↑ Loertscher R, Lavery P (2002). "The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation". Transplant immunology. 9 (2–4): 93–96. doi:10.1016/s0966-3274(02)00013-8. PMID 12180852.

Further reading

  • Wong YW, Williams AF, Kingsmore SF, Seldin MF (1990). "Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3". J. Exp. Med. 171 (6): 2115–30. doi:10.1084/jem.171.6.2115. PMC 2187942. PMID 1693656.
  • Fisher RC, Thorley-Lawson DA (1991). "Characterization of the Epstein-Barr virus-inducible gene encoding the human leukocyte adhesion and activation antigen BLAST-1 (CD48)". Mol. Cell. Biol. 11 (3): 1614–23. PMC 369456. PMID 1847502.
  • Korínek V, Stefanová I, Angelisová P, Hilgert I, Horejsí V (1991). "The human leucocyte antigen CD48 (MEM-102) is closely related to the activation marker Blast-1". Immunogenetics. 33 (2): 108–12. doi:10.1007/BF00210823. PMID 1999350.
  • Garnett D, Barclay AN, Carmo AM, Beyers AD (1993). "The association of the protein tyrosine kinases p56lck and p60fyn with the glycosyl phosphatidylinositol-anchored proteins Thy-1 and CD48 in rat thymocytes is dependent on the state of cellular activation". Eur. J. Immunol. 23 (10): 2540–4. doi:10.1002/eji.1830231024. PMID 8104794.
  • Maruyama K, Sugano S (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.
  • Solomon KR, Rudd CE, Finberg RW (1996). "The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 93 (12): 6053–8. doi:10.1073/pnas.93.12.6053. PMC 39187. PMID 8650218.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (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.
  • Smith GM, Biggs J, Norris B, Anderson-Stewart P, Ward R (1998). "Detection of a soluble form of the leukocyte surface antigen CD48 in plasma and its elevation in patients with lymphoid leukemias and arthritis". J. Clin. Immunol. 17 (6): 502–9. doi:10.1023/A:1027327912204. PMID 9418191.
  • Latchman Y, McKay PF, Reiser H (1998). "Identification of the 2B4 molecule as a counter-receptor for CD48". J. Immunol. 161 (11): 5809–12. PMID 9834056.
  • Nakajima H, Cella M, Langen H, Friedlein A, Colonna M (1999). "Activating interactions in human NK cell recognition: the role of 2B4-CD48". Eur. J. Immunol. 29 (5): 1676–83. doi:10.1002/(SICI)1521-4141(199905)29:05<1676::AID-IMMU1676>3.0.CO;2-Y. PMID 10359122.
  • Shin JS, Abraham SN (2001). "Glycosylphosphatidylinositol-anchored receptor-mediated bacterial endocytosis". FEMS Microbiol. Lett. 197 (2): 131–8. doi:10.1111/j.1574-6968.2001.tb10594.x. PMID 11313125.
  • Tangye SG, Cherwinski H, Lanier LL, Phillips JH (2001). "2B4-mediated activation of human natural killer cells". Mol. Immunol. 37 (9): 493–501. doi:10.1016/S0161-5890(00)00076-6. PMID 11163399.
  • Suzuki T, Kiyokawa N, Taguchi T, Sekino T, Katagiri YU, Fujimoto J (2001). "CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system". J. Immunol. 166 (9): 5567–77. doi:10.4049/jimmunol.166.9.5567. PMID 11313396.
  • Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML (2002). "The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling". Biochim. Biophys. Acta. 1589 (2): 140–50. doi:10.1016/S0167-4889(02)00165-9. PMID 12007789.
  • Kim D, Hur DY, Kim YS, Lee K, Lee Y, Cho D, Kang JS, Kim YI, Hahm E, Yang Y, Yoon S, Kim S, Lee WB, Park HY, Kim YB, Hwang YI, Chang KY, Lee WJ (2002). "CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells". Hum. Immunol. 63 (7): 576–87. doi:10.1016/S0198-8859(02)00405-6. PMID 12072193.
  • Zhu B, Davies EA, van der Merwe PA, Calvert T, Leckband DE (2002). "Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48". Biochemistry. 41 (40): 12163–70. doi:10.1021/bi020296g. PMID 12356317.
  • Wei J (2005). "Expression and characterisation of recombinant human CD48 and isolation of a human anti-CD48 monoclonal antibody by phage display". Journal of Chemical Technology and Biotechnology. 80 (7): 782–795. doi:10.1002/jctb.1238.
  • Wei J (2008). "Cytotoxic Activity of CD48 Monoclonal Antibodies Against Human Lymphoma Cells". The Open Biotechnology Journal. 2: 219–223. doi:10.2174/1874070700802010219.

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