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.[1]
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.[4][5] 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.[6][7] The GPI linkage of CD48 to the cell surface is through serine residue 220.[6][7] 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.[1] The CD48 protein is heavily glycosylated, with five possible asparagine-linked glycosylation sites at positions 40, 44, 104, 162 and 189, respectively.[2][3][4][8][9] Approximately 35-40% of the total molecular weight is attributed to the carbohydrate side chains.[8][9][10]
Interactions
CD48 was found to have a very low affinity for CD2 with dissociation constant (<math>K_{D}</math>) < 0.5 mM.[11] 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 <math>K_{D}</math> = 8 μM which is about 5 - 10 times stronger than for CD2.[12][13][14]
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.[16] 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.[17][18]
Clinical Significance
CD48 is being investigated amongst other markers in research on inflammation markers and therapies for HIV/AIDS.
↑ 2.02.1Thorley-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. PMID6291768.
↑ 3.03.13.2Yokoyama 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. PMID1848579.
↑ 4.04.14.2Vaughan 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. PMID1999351.
↑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. PMID7691954.
↑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. PMID10556801.
↑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. PMID10658976.
↑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. PMID2088634.
↑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. PMID12180852.
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. PMID1999350.
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. PMID8104794.
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. PMID8125298.
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. PMID9373149.
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. PMID9418191.
Latchman Y, McKay PF, Reiser H (1998). "Identification of the 2B4 molecule as a counter-receptor for CD48". J. Immunol. 161 (11): 5809–12. PMID9834056.
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. PMID11313396.
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. PMID12007789.
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. PMID12072193.
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. PMID12356317.
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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