CD5 (protein)

CD5 is a cluster of differentiation expressed on the surface of T cells (various species) 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 (such as bacterial proteins) and not by normal tissue proteins. CD5 was used as a T-cell marker until monoclonal antibodies against CD3 were developed.

CD5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JA4, 2JOP, 2JP0, 2OTT
Identifiers
Aliases	CD5, LEU1, T1, CD5 molecule
External IDs	OMIM: 153340 MGI: 88340 HomoloGene: 7260 GeneCards: CD5
Gene location (Human) Chr. Chromosome 11 (human) Band 11q12.2 Start 61,102,489 bp End 61,127,852 bp
Gene location (Mouse) Chr. Chromosome 19 (mouse) Band 19 A|19 7.16 cM Start 10,694,480 bp End 10,716,366 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lymph node blood appendix thymus spleen bone marrow cells gallbladder thymus tongue superior surface of tongue Top expressed in thymus blood spleen secondary oocyte esophagus lip subcutaneous adipose tissue submandibular gland mammary gland white adipose tissue More reference expression data BioGPS More reference expression data
Gene ontology Molecular function scavenger receptor activity protein binding transmembrane signaling receptor activity signaling receptor activity Cellular component integral component of membrane plasma membrane integral component of plasma membrane membrane external side of plasma membrane Biological process apoptotic signaling pathway T cell costimulation cell population proliferation cell recognition receptor-mediated endocytosis vesicle-mediated transport endocytosis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 921 12507 Ensembl ENSG00000110448 ENSMUSG00000024669 UniProt P06127 P13379 RefSeq (mRNA) NM_014207 NM_001346456 NM_007650 RefSeq (protein) NP_001333385 NP_055022 NP_031676 Location (UCSC) Chr 11: 61.1 – 61.13 Mb Chr 19: 10.69 – 10.72 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

In humans, the gene is located on the long arm of chromosome 11. There is no confirmed ligand for CD5 but there is evidence that CD72, a C-type lectin, may be a ligand or that CD5 may be homophilic, binding CD5 on the surface of other cells. CD5 includes a scavenger receptor cysteine-rich protein domain.

T cells express higher levels of CD5 than B cells. CD5 is upregulated on T cells upon strong activation. In the thymus, there is a correlation with CD5 expression and strength of the interaction of the T cell towards self-peptides.

Immunohistochemistry

CD5 is a good immunohistochemical marker for T-cells, although not as sensitive as CD3. About 76% of T-cell neoplasms are reported to express CD5, and it is also found in chronic lymphocytic leukemia and mantle cell lymphoma (both being B cell malignancies), that do not express CD3. It is commonly lost in cutaneous T-cell lymphoma, and its absence can be used as an indicator of malignancy in this condition. The absence of CD5 in T cell acute lymphoblastic leukemia, while relatively rare, is associated with a poor prognosis.

Further reading

• Berland R, Wortis HH (2002). "Origins and functions of B-1 cells with notes on the role of CD5". Annu. Rev. Immunol. 20: 253–300. doi:10.1146/annurev.immunol.20.100301.064833. PMID 11861604.
• Osman N, Ley SC, Crumpton MJ (1992). "Evidence for an association between the T cell receptor/CD3 antigen complex and the CD5 antigen in human T lymphocytes". Eur. J. Immunol. 22 (11): 2995–3000. doi:10.1002/eji.1830221135. PMID 1385158. S2CID 34625072.
• Van de Velde H, von Hoegen I, Luo W, Parnes JR, Thielemans K (1991). "The B-cell surface protein CD72/Lyb-2 is the ligand for CD5". Nature. 351 (6328): 662–5. Bibcode:1991Natur.351..662D. doi:10.1038/351662a0. PMID 1711157. S2CID 4342866.
• Jones NH, Clabby ML, Dialynas DP, Huang HJ, Herzenberg LA, Strominger JL (1986). "Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1". Nature. 323 (6086): 346–9. Bibcode:1986Natur.323..346J. doi:10.1038/323346a0. PMID 3093892. S2CID 4361866.
• Lankester AC, van Schijndel GM, Cordell JL, van Noesel CJ, van Lier RA (1994). "CD5 is associated with the human B cell antigen receptor complex". Eur. J. Immunol. 24 (4): 812–6. doi:10.1002/eji.1830240406. PMID 7512031. S2CID 25093082.
• Raab M, Yamamoto M, Rudd CE (1994). "The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck". Mol. Cell. Biol. 14 (5): 2862–70. doi:10.1128/mcb.14.5.2862. PMC 358654. PMID 7513045.
• Dianzani U, Bragardo M, Buonfiglio D, Redoglia V, Funaro A, Portoles P, Rojo J, Malavasi F, Pileri A (1995). "Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120". Eur. J. Immunol. 25 (5): 1306–11. doi:10.1002/eji.1830250526. PMID 7539755. S2CID 37717142.
• Van de Velde H, Thielemans K (1996). "Native soluble CD5 delivers a costimulatory signal to resting human B lymphocytes". Cell. Immunol. 172 (1): 84–91. doi:10.1006/cimm.1996.0218. PMID 8806810.
• Dennehy KM, Broszeit R, Garnett D, Durrheim GA, Spruyt LL, Beyers AD (1997). "Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5". Eur. J. Immunol. 27 (3): 679–86. doi:10.1002/eji.1830270316. PMID 9079809. S2CID 41540340.
• Gary-Gouy H, Lang V, Sarun S, Boumsell L, Bismuth G (1997). "In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes". J. Immunol. 159 (8): 3739–47. doi:10.4049/jimmunol.159.8.3739. PMID 9378960. S2CID 42470132.
• Dennehy KM, Broszeit R, Ferris WF, Beyers AD (1998). "Thymocyte activation induces the association of the proto-oncoprotein c-cbl and ras GTPase-activating protein with CD5". Eur. J. Immunol. 28 (5): 1617–25. doi:10.1002/(SICI)1521-4141(199805)28:05<1617::AID-IMMU1617>3.0.CO;2-7. PMID 9603468.
• Bauch A, Campbell KS, Reth M (1998). "Interaction of the CD5 cytoplasmic domain with the Ca2+/calmodulin-dependent kinase IIdelta". Eur. J. Immunol. 28 (7): 2167–77. doi:10.1002/(SICI)1521-4141(199807)28:07<2167::AID-IMMU2167>3.0.CO;2-L. PMID 9692886.
• Calvo J, Vildà JM, Places L, Simarro M, Padilla O, Andreu D, Campbell KS, Aussel C, Lozano F (1998). "Human CD5 signaling and constitutive phosphorylation of C-terminal serine residues by casein kinase II". J. Immunol. 161 (11): 6022–9. doi:10.4049/jimmunol.161.11.6022. PMID 9834084. S2CID 24141284.
• McAlister MS, Davis B, Pfuhl M, Driscoll PC (1999). "NMR analysis of the N-terminal SRCR domain of human CD5: engineering of a glycoprotein for superior characteristics in NMR experiments". Protein Eng. 11 (10): 847–53. doi:10.1093/protein/11.10.847. PMID 9862202.
• Perez-Villar JJ, Whitney GS, Bowen MA, Hewgill DH, Aruffo AA, Kanner SB (1999). "CD5 negatively regulates the T-cell antigen receptor signal transduction pathway: involvement of SH2-containing phosphotyrosine phosphatase SHP-1". Mol. Cell. Biol. 19 (4): 2903–12. doi:10.1128/mcb.19.4.2903. PMC 84084. PMID 10082557.
• Carmo AM, Castro MA, Arosa FA (1999). "CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells". J. Immunol. 163 (8): 4238–45. doi:10.4049/jimmunol.163.8.4238. PMID 10510361. S2CID 21192459.
• Vilà JM, Calvo J, Places L, Padilla O, Arman M, Gimferrer I, Aussel C, Vives J, Lozano F (2001). "Role of two conserved cytoplasmic threonine residues (T410 and T412) in CD5 signaling". J. Immunol. 166 (1): 396–402. doi:10.4049/jimmunol.166.1.396. PMID 11123317.
• Vilà JM, Gimferrer I, Padilla O, Arman M, Places L, Simarro M, Vives J, Lozano F (2001). "Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases". Eur. J. Immunol. 31 (4): 1191–8. doi:10.1002/1521-4141(200104)31:4<1191::AID-IMMU1191>3.0.CO;2-H. PMID 11298344.
• Kirchgessner H, Dietrich J, Scherer J, Isomäki P, Korinek V, Hilgert I, Bruyns E, Leo A, Cope AP, Schraven B (2001). "The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain". J. Exp. Med. 193 (11): 1269–84. doi:10.1084/jem.193.11.1269. PMC 2193385. PMID 11390434.
• Gary-Gouy H, Harriague J, Dalloul A, Donnadieu E, Bismuth G (2002). "CD5-negative regulation of B cell receptor signaling pathways originates from tyrosine residue Y429 outside an immunoreceptor tyrosine-based inhibitory motif". J. Immunol. 168 (1): 232–9. doi:10.4049/jimmunol.168.1.232. PMID 11751967.
• Mier-Aguilar CA, Vega-Baray B, Burgueño-Bucio E, Lozano F, García-Zepeda EA, Raman C, Soldevila G (2015). "Functional requirement of tyrosine residue 429 within CD5 cytoplasmic domain for regulation of T cell activation and survival". Biochem Biophys Res Commun. 466 (3): 381–7. doi:10.1016/j.bbrc.2015.09.033. PMID 26363459.

External links

• CD5+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CD5 genome location and CD5 gene details page in the UCSC Genome Browser.