CD48

Last updated
CD48
CD48 protein.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CD48 , BCM1, BLAST, BLAST1, MEM-102, SLAMF2, hmCD48 molecule
External IDs OMIM: 109530; MGI: 88339; HomoloGene: 1347; GeneCards: CD48; OMA:CD48 - orthologs
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 Mb Chr 1: 171.51 – 171.53 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Contents

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 transduction via GPI moieties. [21] [22]

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. [23]

See also

Related Research Articles

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A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">Superantigen</span> Antigen which strongly activates the immune system

Superantigens (SAgs) are a class of antigens that result in excessive activation of the immune system. Specifically they cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. Superantigens act by binding to the MHC proteins on antigen-presenting cells (APCs) and to the TCRs on their adjacent helper T-cells, bringing the signaling molecules together, and thus leading to the activation of the T-cells, regardless of the peptide displayed on the MHC molecule. SAgs are produced by some pathogenic viruses and bacteria most likely as a defense mechanism against the immune system. Compared to a normal antigen-induced T-cell response where 0.0001-0.001% of the body's T-cells are activated, these SAgs are capable of activating up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens.

<span class="mw-page-title-main">Integrin alpha X</span> Mammalian protein found in Homo sapiens

CD11c, also known as Integrin, alpha X (ITGAX), is a gene that encodes for CD11c.

<span class="mw-page-title-main">Integrin alpha L</span> Mammalian protein found in Homo sapiens

Integrin, alpha L , also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene. CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.

<span class="mw-page-title-main">CD90</span> Mammalian protein found in Homo sapiens

Thy-1 or CD90 is a 25–37 kDa heavily N-glycosylated, glycophosphatidylinositol (GPI) anchored conserved cell surface protein with a single V-like immunoglobulin domain, originally discovered as a thymocyte antigen. Thy-1 can be used as a marker for a variety of stem cells and for the axonal processes of mature neurons. Structural study of Thy-1 led to the foundation of the Immunoglobulin superfamily, of which it is the smallest member, and led to some of the initial biochemical description and characterization of a vertebrate GPI anchor and also the first demonstration of tissue specific differential glycosylation.

<span class="mw-page-title-main">CD2</span> Cell adhesion molecule found on the surface of T cells and natural killer

CD2 is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette receptor.

<span class="mw-page-title-main">CD43</span> Mammalian protein found in Homo sapiens

Leukosialin also known as sialophorin or CD43 is a transmembrane cell surface protein that in humans is encoded by the SPN (sialophorin) gene.

<span class="mw-page-title-main">CD59</span> Mammalian protein found in Homo sapiens

CD59 glycoprotein, also known as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is a protein that in humans is encoded by the CD59 gene. It is an LU domain and belongs to the LY6/uPAR/alpha-neurotoxin protein family.

<span class="mw-page-title-main">CD5 (protein)</span> Protein-coding gene in the species Homo sapiens

CD5 is a cluster of differentiation expressed on the surface of T cells and in a subset of murine B cells known as B-1a. The expression of this receptor in human B cells has been a controversial topic and to date there is no consensus regarding the role of this receptor as a marker of human B cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase (TdT) and are potentially self-reactive. CD5 serves to mitigate activating signals from the BCR so that the B-1 cells can only be activated by very strong stimuli and not by normal tissue proteins. CD5 was used as a T-cell marker until monoclonal antibodies against CD3 were developed.

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.

<span class="mw-page-title-main">CD53</span> Mammalian protein found in Homo sapiens

Leukocyte surface antigen CD53 is a protein that in humans is encoded by the CD53 gene.

<span class="mw-page-title-main">ICAM3</span> Mammalian protein found in Homo sapiens

Intercellular adhesion molecule 3 (ICAM3) also known as CD50, is a protein that in humans is encoded by the ICAM3 gene. The protein is constitutively expressed on the surface of leukocytes, which are also called white blood cells and are part of the immune system. ICAM3 mediates adhesion between cells by binding to specific integrin receptors. It plays an important role in the immune cell response through its facilitation of interactions between T cells and dendritic cells, which allows for T cell activation. ICAM3 also mediates the clearance of cells undergoing apoptosis by attracting and binding macrophages, a type of cell that breaks down infected or dying cells through a process known as phagocytosis, to apoptotic cells.

<span class="mw-page-title-main">CD3G</span> Protein-coding gene in the species Homo sapiens

T-cell surface glycoprotein CD3 gamma chain is a protein that in humans is encoded by the CD3G gene.

<span class="mw-page-title-main">CD244</span> Protein found in humans

CD244 also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.

<span class="mw-page-title-main">SEMA4D</span>

Semaphorin-4D (SEMA4D) also known as Cluster of Differentiation 100 (CD100), is a protein of the semaphorin family that in humans is encoded by the SEMA4D gene.

<span class="mw-page-title-main">CD84</span> Protein found in humans

CD84 is a human protein encoded by the CD84 gene.

<span class="mw-page-title-main">SLAMF6</span> Protein-coding gene in humans

SLAM family member 6 is a protein that in humans is encoded by the SLAMF6 gene.

<span class="mw-page-title-main">CD6</span> Human protein

CD6 is a human protein encoded by the CD6 gene.

<span class="mw-page-title-main">CD8A</span> Protein-coding gene in the species Homo sapiens

T-cell surface glycoprotein CD8 alpha chain, is a protein encoded by CD8A gene.

Ly6 also known as lymphocyte antigen 6 or urokinase-type plasminogen activator receptor (uPAR) is family of proteins that share a common structure but differ in their tissue expression patterns and function. Ly6 are cysteine-rich proteins that form disulfide bridges and contain a LU domain. These proteins are GPI-anchored to the cell membrane or are secreted. A total of 35 human and 61 mouse Ly6 family members have been identified. Depending on which tissues they are expressed in, LY6 family members have different roles. They are expressed in various types of tissues and their expression dependent on the stage of cell differentiation. For example, they are involved in cell proliferation, cell migration, cell–cell interactions, immune cell maturation, macrophage activation, and cytokine production. Their overexpression or dysregulation, for example due to point mutations, is associated with tumorogenesis and autoimmune diseases. This family was discovered in the 1970s, and these proteins are still used as markers of distinct stage of leukocyte differentiation.

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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. S2CID   45406805.
  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. doi:10.4049/jimmunol.146.7.2192. PMID   1848579. S2CID   13131389.
  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. S2CID   32479661.
  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. doi:10.1002/j.1460-2075.1988.tb03174.x. 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. doi:10.1002/j.1460-2075.1987.tb02703.x. 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. S2CID   40061476.
  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. doi: 10.4049/jimmunol.151.9.4606 . PMID   7691954. S2CID   37921171.
  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. S2CID   5731764.
  21. ↑ Mulvey MA, Hultgren SJ (2000). "Cell biology. Bacterial spelunkers". Science. 289 (5480): 732–733. doi:10.1126/science.289.5480.732. PMID   10950716. S2CID   43466889.
  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.
  23. ↑ 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

Further reading

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