View source for CD48

{{Short description|Protein-coding gene in humans}}
{{Infobox_gene}}
'''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]].<ref name="entrez">{{cite web | title = Entrez Gene: CD48 CD48 molecule| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=962}}</ref>

CD48 is a member of the [[CD2]] subfamily of the [[immunoglobulin superfamily]] (IgSF) which includes [[signaling lymphocytic activation molecule|SLAM]] (signaling lymphocyte activation molecules) proteins, such as [[CD84]], [[CD150]], [[CD229]] and [[CD244]]. CD48 is found on the surface of [[lymphocyte]]s and other immune cells, [[dendritic cell]]s and [[endothelial cell]]s, and participates in activation and differentiation pathways in these cells.<ref name="entrez"/>

CD48 was the first B-cell-specific [[cellular differentiation]] [[antigen]] identified in transformed B [[lymphoblast]]s.<ref name="pmid6291768">{{cite journal | vauthors = Thorley-Lawson DA, Schooley RT, Bhan AK, Nadler LM | title = Epstein-Barr virus superinduces a new human B cell differentiation antigen (B-LAST 1) expressed on transformed lymphoblasts | journal = Cell | volume = 30 | issue = 2 | pages = 415–25 | date = September 1982 | pmid = 6291768 | doi = 10.1016/0092-8674(82)90239-2 | s2cid = 45406805 }}</ref><ref name="pmid1848579">{{cite journal | vauthors = Yokoyama S, Staunton D, Fisher R, Amiot M, Fortin JJ, Thorley-Lawson DA | title = Expression of the Blast-1 activation/adhesion molecule and its identification as CD48 | journal = J. Immunol. | volume = 146 | issue = 7 | pages = 2192–200 | date = April 1991 | doi = 10.4049/jimmunol.146.7.2192 | pmid = 1848579 | s2cid = 13131389 }}</ref>

==Structure==

The gene for CD48 is located in [[chromosome 1]]q23 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.<ref name="pmid1999351"/><ref name="pmid1827826">{{cite journal | vauthors = Del Porto P, Mami-Chouaib F, Bruneau JM, Jitsukawa S, Dumas J, Harnois M, Hercend T | title = 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 | journal = J. Exp. Med. | volume = 173 | issue = 6 | pages = 1339–44 | date = June 1991 | pmid = 1827826 | pmc = 2190850 | doi = 10.1084/jem.173.6.1339 }}</ref> 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]].<ref name="pmid3181129">{{cite journal | vauthors = Killeen N, Moessner R, Arvieux J, Willis A, Williams AF | title = 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 | journal = EMBO J. | volume = 7 | issue = 10 | pages = 3087–91 | date = October 1988 | pmid = 3181129 | pmc = 454697 | doi =  10.1002/j.1460-2075.1988.tb03174.x}}</ref><ref name="pmid2466936">{{cite journal | vauthors = Staunton DE, Fisher RC, LeBeau MM, Lawrence JB, Barton DE, Francke U, Dustin M, Thorley-Lawson DA | title = Blast-1 possesses a glycosyl-phosphatidylinositol (GPI) membrane anchor, is related to LFA-3 and OX-45, and maps to chromosome 1q21-23 | journal = J. Exp. Med. | volume = 169 | issue = 3 | pages = 1087–99 | date = March 1989 | pmid = 2466936 | pmc = 2189294 | doi = 10.1084/jem.169.3.1087 }}</ref> The GPI linkage of CD48 to the cell surface is through serine residue 220.<ref name="pmid3181129"/><ref name="pmid2466936"/> CD48 does not have a [[transmembrane]] domain, however, but is held at the cell surface by a [[glycophosphatidylinositol|GPI]] anchor via a [[C-terminal]] domain which can be cleaved to yield a soluble form of the receptor.<ref name="entrez"/>  The CD48 protein is heavily [[glycosylated]], with five possible asparagine-linked [[glycosylation]] sites at positions 40, 44, 104, 162 and 189, respectively.<ref name="pmid6291768"/><ref name="pmid1848579"/><ref name="pmid1999351">{{cite journal | vauthors = Vaughan HA, Henning MM, Purcell DF, McKenzie IF, Sandrin MS | title = The isolation of cDNA clones for CD48 | journal = Immunogenetics | volume = 33 | issue = 2 | pages = 113–7 | year = 1991 | pmid = 1999351 | doi = 10.1007/BF00210824 | s2cid = 32479661 }}</ref><ref name="pmid2828034">{{cite journal | vauthors = Staunton DE, Thorley-Lawson DA | title = Molecular cloning of the lymphocyte activation marker Blast-1 | journal = EMBO J. | volume = 6 | issue = 12 | pages = 3695–701 | date = December 1987 | pmid = 2828034 | pmc = 553839 | doi =  10.1002/j.1460-2075.1987.tb02703.x}}</ref><ref name="pmid10529350">{{cite journal | vauthors = Rudd PM, Wormald MR, Stanfield RL, Huang M, Mattsson N, Speir JA, DiGennaro JA, Fetrow JS, Dwek RA, Wilson IA | title = Roles for glycosylation of cell surface receptors involved in cellular immune recognition | journal = J. Mol. Biol. | volume = 293 | issue = 2 | pages = 351–66 | date = October 1999 | pmid = 10529350 | doi = 10.1006/jmbi.1999.3104 }}</ref> Approximately 35-40% of the total molecular weight is attributed to the carbohydrate side chains.<ref name="pmid2828034"/><ref name="pmid10529350"/><ref name="pmid6623618">{{cite journal | vauthors = Vaughan HA, Thompson CH, Sparrow RL, McKenzie IF | title = Hu Ly-M3--a human leukocyte antigen | journal = Transplantation | volume = 36 | issue = 4 | pages = 446–50 | date = October 1983 | pmid = 6623618 | doi = 10.1097/00007890-198310000-00018 | s2cid = 40061476 | doi-access = free }}</ref>

== Interactions ==
CD48 was found to have a very low affinity for [[CD2]] with [[dissociation constant]] (<math>K_{D}</math>) < 0.5 mM.<ref>{{cite journal | vauthors = Sandrin MS, Mouhtouris E, Vaughan HA, Warren HS, Parish CR | title = CD48 is a low affinity ligand for human CD2 | journal = J. Immunol. | volume = 151 | issue = 9 | pages = 4606–13 | date = November 1993 | doi = 10.4049/jimmunol.151.9.4606 | pmid = 7691954 | s2cid = 37921171 | doi-access = free }}</ref>  It was found that the preferred ligand of CD48 is [[2B4]] ([[CD244]]), which is also a member of the CD2 subfamily [[signaling lymphocytic activation molecule|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.<ref>{{cite journal | vauthors = Brown MH, Boles K, van der Merwe PA, Kumar V, Mathew PA, Barclay AN | title = 2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48 | journal = J. Exp. Med. | volume = 188 | issue = 11 | pages = 2083–90 | date = December 1998 | pmid = 9841922 | pmc = 2212392 | doi = 10.1084/jem.188.11.2083 }}</ref><ref>{{cite journal | vauthors = 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 | title = Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48 | journal = Eur. J. Immunol. | volume = 29 | issue = 11 | pages = 3466–77 | date = November 1999 | pmid = 10556801 | doi = 10.1002/(SICI)1521-4141(199911)29:11<3466::AID-IMMU3466>3.0.CO;2-9 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Nakajima H, Colonna M | title = 2B4: an NK cell activating receptor with unique specificity and signal transduction mechanism | journal = Hum. Immunol. | volume = 61 | issue = 1 | pages = 39–43 | date = January 2000 | pmid = 10658976 | doi = 10.1016/s0198-8859(99)00170-6 }}</ref>

== Function ==

=== Cell distribution ===

CD48 is expressed on all [[peripheral blood lymphocytes]] (PBL) including [[T cells]], [[B cells]], NK cells and [[thymocytes]].<ref name="pmid1848579"/><ref name="pmid1999351"/><ref name="pmid6623618"/><ref name="pmid2088634">{{cite journal | vauthors = Henniker AJ, Bradstock KF, Grimsley P, Atkinson MK | title = A novel non-lineage antigen on human leucocytes: characterization with two CD-48 monoclonal antibodies | journal = Dis. Markers | volume = 8 | issue = 4 | pages = 179–90 | year = 1990 | pmid = 2088634 }}</ref> It is also found on the surface of activated T cells, mast cells, [[monocytes]] and [[granulocytes]].<ref name="pmid2828034"/> Like all other [[Glycophosphatidylinositol|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]].<ref name="pmid10428718">{{cite journal | vauthors = Malissen B | title = Dancing the immunological two-step | journal = Science | volume = 285 | issue = 5425 | pages = 207–208 | year = 1999 | pmid = 10428718 | doi = 10.1126/science.285.5425.207 | s2cid = 5731764 }}</ref>  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 transduction via GPI moieties.<ref name="pmid10950716">{{cite journal | vauthors = Mulvey MA, Hultgren SJ | title = Cell biology. Bacterial spelunkers | journal = Science | volume = 289 | issue = 5480 | pages = 732–733 | year = 2000 | pmid = 10950716 | doi = 10.1126/science.289.5480.732 | s2cid = 43466889 }}</ref><ref name="pmid12180852">{{cite journal | vauthors = Loertscher R, Lavery P | title = The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation | journal = Transplant Immunology | volume = 9 | issue = 2–4 | pages = 93–96 | year = 2002 | pmid = 12180852 | doi=10.1016/s0966-3274(02)00013-8}}</ref>

==Clinical significance==

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

Heterozygous [[germline mutation]] in a patient was associated with a recurrent inflammatory syndrome resembling hemophagocytic lymphohistiocytosis.<ref>Volkmer B, Planas R, Gossweiler E,  Opitz L, Mauracher A, Nüesch U, Gayden T, Kaiser D, Drexel B, Dumrese C, Jabado N, Vavassori S, Pachlopnik Schmid J: Recurrent inflammatory disease caused by a heterozygous mutation in CD48. ''J Allergy Clin Immunol''. 2019;144(5):1441-1445.e17. doi:10.1016/j.jaci.[[doi:10.1016/j.jaci.2019.07.038]]</ref>

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== See also ==
* [[Cluster of differentiation]]

== [[Reference]]s ==
{{reflist | 2}}{{Clear}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Wong YW, Williams AF, Kingsmore SF, Seldin MF | title = 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 | journal = J. Exp. Med. | volume = 171 | issue = 6 | pages = 2115–30 | year = 1990 | pmid = 1693656 | pmc = 2187942 | doi = 10.1084/jem.171.6.2115 }}
* {{cite journal | vauthors = Fisher RC, Thorley-Lawson DA | title = Characterization of the Epstein-Barr virus-inducible gene encoding the human leukocyte adhesion and activation antigen BLAST-1 (CD48) | journal = Mol. Cell. Biol. | volume = 11 | issue = 3 | pages = 1614–23 | year = 1991 | pmid = 1847502 | pmc = 369456 | doi =  10.1128/MCB.11.3.1614}}
* {{cite journal | vauthors = Korínek V, Stefanová I, Angelisová P, Hilgert I, Horejsí V | title = The human leucocyte antigen CD48 (MEM-102) is closely related to the activation marker Blast-1 | journal = Immunogenetics | volume = 33 | issue = 2 | pages = 108–12 | year = 1991 | pmid = 1999350 | doi = 10.1007/BF00210823 | s2cid = 11414678 }}
* {{cite journal | vauthors = Garnett D, Barclay AN, Carmo AM, Beyers AD | title = 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 | journal = Eur. J. Immunol. | volume = 23 | issue = 10 | pages = 2540–4 | year = 1993 | pmid = 8104794 | doi = 10.1002/eji.1830231024 | s2cid = 9747812 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
* {{cite journal | vauthors = Solomon KR, Rudd CE, Finberg RW | title = The association between glycosylphosphatidylinositol-anchored proteins and heterotrimeric G protein alpha subunits in lymphocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 12 | pages = 6053–8 | year = 1996 | pmid = 8650218 | pmc = 39187 | doi = 10.1073/pnas.93.12.6053 | bibcode = 1996PNAS...93.6053S | doi-access = free }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
* {{cite journal | vauthors = Smith GM, Biggs J, Norris B, Anderson-Stewart P, Ward R | title = Detection of a soluble form of the leukocyte surface antigen CD48 in plasma and its elevation in patients with lymphoid leukemias and arthritis | journal = J. Clin. Immunol. | volume = 17 | issue = 6 | pages = 502–9 | year = 1998 | pmid = 9418191 | doi = 10.1023/A:1027327912204 | s2cid = 2538203 | doi-access = free }}
* {{cite journal | vauthors = Latchman Y, McKay PF, Reiser H | title = Identification of the 2B4 molecule as a counter-receptor for CD48 | journal = J. Immunol. | volume = 161 | issue = 11 | pages = 5809–12 | year = 1998 | doi = 10.4049/jimmunol.161.11.5809 | pmid = 9834056 | s2cid = 7819238 | doi-access = free }}
* {{cite journal | vauthors = Nakajima H, Cella M, Langen H, Friedlein A, Colonna M | title = Activating interactions in human NK cell recognition: the role of 2B4-CD48 | journal = Eur. J. Immunol. | volume = 29 | issue = 5 | pages = 1676–83 | year = 1999 | pmid = 10359122 | doi = 10.1002/(SICI)1521-4141(199905)29:05<1676::AID-IMMU1676>3.0.CO;2-Y | doi-access = free }}
* {{cite journal | vauthors = Shin JS, Abraham SN | title = Glycosylphosphatidylinositol-anchored receptor-mediated bacterial endocytosis. | journal = FEMS Microbiol. Lett. | volume = 197 | issue = 2 | pages = 131–8 | year = 2001 | pmid = 11313125 | doi = 10.1111/j.1574-6968.2001.tb10594.x | doi-access = free }}
* {{cite journal | vauthors = Tangye SG, Cherwinski H, Lanier LL, Phillips JH | title = 2B4-mediated activation of human natural killer cells | journal = Mol. Immunol. | volume = 37 | issue = 9 | pages = 493–501 | year = 2001 | pmid = 11163399 | doi = 10.1016/S0161-5890(00)00076-6 }}
* {{cite journal | vauthors = Suzuki T, Kiyokawa N, Taguchi T, Sekino T, Katagiri YU, Fujimoto J | title = CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system | journal = J. Immunol. | volume = 166 | issue = 9 | pages = 5567–77 | year = 2001 | pmid = 11313396 | doi = 10.4049/jimmunol.166.9.5567 | doi-access = free }}
* {{cite journal | vauthors = Hawash IY, Hu XE, Adal A, Cassady JM, Geahlen RL, Harrison ML | title = The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling | journal = Biochim. Biophys. Acta | volume = 1589 | issue = 2 | pages = 140–50 | year = 2002 | pmid = 12007789 | doi = 10.1016/S0167-4889(02)00165-9 | doi-access = free }}
* {{cite journal | vauthors = 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 | title = CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells and in a mitochondria-controlled manner in Raji cells | journal = Hum. Immunol. | volume = 63 | issue = 7 | pages = 576–87 | year = 2002 | pmid = 12072193 | doi = 10.1016/S0198-8859(02)00405-6 }}
* {{cite journal | vauthors = Zhu B, Davies EA, van der Merwe PA, Calvert T, Leckband DE | title = Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48 | journal = Biochemistry | volume = 41 | issue = 40 | pages = 12163–70 | year = 2002 | pmid = 12356317 | doi = 10.1021/bi020296g }}
*{{cite journal  | author=Wei J  |title=Expression and characterisation of recombinant human CD48 and isolation of a human anti-CD48 monoclonal antibody by phage display |journal=Journal of Chemical Technology and Biotechnology |volume=80 |issue= 7 |pages= 782–795 |year= 2005 |doi=10.1002/jctb.1238  }}
*{{cite journal  | author=Wei J |title=Cytotoxic Activity of CD48 Monoclonal Antibodies Against Human Lymphoma Cells |journal=The Open Biotechnology Journal |volume=2 |pages= 219–223 |year= 2008 |doi= 10.2174/1874070700802010219  |doi-access=free}}
{{refend}}

== External links ==
* {{MeSH name|CD48+protein,+human}}
* {{UCSC gene info|CD48}}

{{NLM content}}
{{Clusters of differentiation}}

[[Category:Clusters of differentiation]]