Biology:CD48

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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]

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.[1]

CD48 was the first B-cell-specific cellular differentiation antigen identified in transformed B lymphoblasts.[2][3]

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.[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]\displaystyle{ 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]\displaystyle{ K_{D} }[/math] = 8 μM which is about 5 - 10 times stronger than for CD2.[12][13][14]

Function

Cell distribution

CD48 is expressed on all peripheral blood lymphocytes (PBL) including T cells, B cells, NK cells and thymocytes.[3][4][10][15] It is also found on the surface of activated T cells, mast cells, monocytes and granulocytes.[8] 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.[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 transduction via GPI moieties.[17][18]

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.[19]


See also

References

  1. ↑ 1.0 1.1 1.2 "Entrez Gene: CD48 CD48 molecule". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=962. 
  2. ↑ 2.0 2.1 "Epstein-Barr virus superinduces a new human B cell differentiation antigen (B-LAST 1) expressed on transformed lymphoblasts". Cell 30 (2): 415–25. September 1982. doi:10.1016/0092-8674(82)90239-2. PMID 6291768. 
  3. ↑ 3.0 3.1 3.2 "Expression of the Blast-1 activation/adhesion molecule and its identification as CD48". J. Immunol. 146 (7): 2192–200. April 1991. doi:10.4049/jimmunol.146.7.2192. PMID 1848579. 
  4. ↑ 4.0 4.1 4.2 "The isolation of cDNA clones for CD48". Immunogenetics 33 (2): 113–7. 1991. doi:10.1007/BF00210824. PMID 1999351. 
  5. ↑ "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. June 1991. doi:10.1084/jem.173.6.1339. PMID 1827826. 
  6. ↑ 6.0 6.1 "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. October 1988. doi:10.1002/j.1460-2075.1988.tb03174.x. PMID 3181129. 
  7. ↑ 7.0 7.1 "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. March 1989. doi:10.1084/jem.169.3.1087. PMID 2466936. 
  8. ↑ 8.0 8.1 8.2 "Molecular cloning of the lymphocyte activation marker Blast-1". EMBO J. 6 (12): 3695–701. December 1987. doi:10.1002/j.1460-2075.1987.tb02703.x. PMID 2828034. 
  9. ↑ 9.0 9.1 "Roles for glycosylation of cell surface receptors involved in cellular immune recognition". J. Mol. Biol. 293 (2): 351–66. October 1999. doi:10.1006/jmbi.1999.3104. PMID 10529350. 
  10. ↑ 10.0 10.1 "Hu Ly-M3--a human leukocyte antigen". Transplantation 36 (4): 446–50. October 1983. doi:10.1097/00007890-198310000-00018. PMID 6623618. 
  11. ↑ "CD48 is a low affinity ligand for human CD2". J. Immunol. 151 (9): 4606–13. November 1993. doi:10.4049/jimmunol.151.9.4606. PMID 7691954. 
  12. ↑ "2B4, the natural killer and T cell immunoglobulin superfamily surface protein, is a ligand for CD48". J. Exp. Med. 188 (11): 2083–90. December 1998. doi:10.1084/jem.188.11.2083. PMID 9841922. 
  13. ↑ "Molecular cloning and biological characterization of NK cell activation-inducing ligand, a counterstructure for CD48". Eur. J. Immunol. 29 (11): 3466–77. November 1999. doi:10.1002/(SICI)1521-4141(199911)29:11<3466::AID-IMMU3466>3.0.CO;2-9. PMID 10556801. 
  14. ↑ "2B4: an NK cell activating receptor with unique specificity and signal transduction mechanism". Hum. Immunol. 61 (1): 39–43. January 2000. doi:10.1016/s0198-8859(99)00170-6. PMID 10658976. 
  15. ↑ "A novel non-lineage antigen on human leucocytes: characterization with two CD-48 monoclonal antibodies". Dis. Markers 8 (4): 179–90. 1990. PMID 2088634. 
  16. ↑ "Dancing the immunological two-step". Science 285 (5425): 207–208. 1999. doi:10.1126/science.285.5425.207. PMID 10428718. 
  17. ↑ "Cell biology. Bacterial spelunkers". Science 289 (5480): 732–733. 2000. doi:10.1126/science.289.5480.732. PMID 10950716. 
  18. ↑ "The role of glycosyl phosphatidyl inositol (GPI)-anchored cell surface proteins in T-cell activation". Transplant Immunology 9 (2–4): 93–96. 2002. doi:10.1016/s0966-3274(02)00013-8. PMID 12180852. 
  19. ↑ 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

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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