Alternative titles; symbols
HGNC Approved Gene Symbol: CD5
Cytogenetic location: 11q12.2 Genomic coordinates (GRCh38): 11:61,093,963-61,127,852 (from NCBI)
The T1/LEU1/CD5 molecule, a human T-cell surface glycoprotein of relative molecular mass 67,000, has been implicated in the proliferative response of activated T cells and in T-cell helper function. Ly1 is the murine homolog (Jones et al., 1986).
Jones et al. (1986) reported the complete amino acid sequence of the CD5 precursor molecule deduced from cDNA clones. The protein contains a classic signal peptide, a 347-amino acid extracellular segment, a transmembrane region, and a 93-amino acid intracellular segment. Southern blot analysis suggested that the T1 molecule is encoded by a single-copy gene. Bierer et al. (1988) showed that a small portion of T lymphocytes are negative for CD5 yet have a normal lymphoid phenotype, i.e., express normal cytolytic activity.
Van Dongen et al. (1985) assigned CD5 to chromosome 11 by somatic cell hybrids created by fusion of a murine T-cell line with cells from a patient with T-cell acute lymphoblastic leukemia. Hecht et al. (1989) used in situ hybridization to localize the CD5 gene to human chromosome 11q13.
In a review of immune inhibitory receptors, Ravetch and Lanier (2000) pointed out that autoimmune disorders may result from the disruption of inhibitory receptors, particularly in their conserved intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). ITIMs are sites for alternative phosphorylation, typically by a Src kinase, and dephosphorylation, either by the tyrosine phosphatase SHP1 (176883) or the inositol phosphatase SHIP (601582), transducing signals to distinct pathways. Ravetch and Lanier (2000) noted that CD5 has an ITIM that interacts with SHP1 and opposes activation mediated by the B cell receptor.
Lundell et al. (2014) performed flow cytometric analysis and ELISA of cord blood and peripheral blood obtained up to age 36 months from a cohort of rural Swedish children and compared the findings with unrelated cord blood samples and peripheral blood from unrelated older children and adults. The authors determined proportions of immature CD5-positive and mature CD27 (TNFRSF7; 186711)-positive B lymphocytes and levels of IgM, IgG, IgA, and IgE. Most CD5-positive cells expressed an immature phenotype, with high levels of CD24 (600074) and CD38 (107270), although the level of immature CD5-positive cells declined somewhat with increasing age. Infants with a high proportion of CD5-positive B cells at birth and 1 month of age had an increased risk of allergic disease at 18 and 36 months of age. Proportions of CD5-positive B cells at 1 month of age were inversely correlated with total IgG levels at 18 and 36 months of age. Lundell et al. (2014) proposed that development of allergic disease is preceded by immaturity in the neonatal B-cell phenotype.
By flow cytometric analysis, Zhang et al. (2016) demonstrated that the proportion of mouse B cells expressing Cd5 relative to those expressing Il6ra (147880) was greatly increased in tumors. Western blot analysis showed that Cd5-positive B cells responded to Il6 (147620) in the absence of Il6ra. Binding of Il6 to Cd5 led to Stat3 (102582) activation via gp130 (IL6ST; 600694) and its downstream kinase Jak2 (147796). Stat3 upregulated Cd5 expression, forming a feed-forward loop in B cells. In mouse tumor models, Cd5-positive B cells, but not Cd5-negative B cells, promoted tumor growth. CD5-positive B cells also showed activation of STAT3 in multiple types of human tumor tissues. Zhang et al. (2016) concluded that CD5-positive B cells play a critical role in promoting cancer.
In the mouse, lymphocyte surface antigens that are markers for function have been identified. Allelic forms are known and chromosomal assignment of the loci has been achieved (Gershon, 1978). Ly1 is on mouse chromosome 19. Ly2 and Ly3 are on mouse chromosome 6 (see 186730). Ly5 is on mouse chromosome 1 (see 151460). Ly6 is on mouse chromosome 15 (LeClair et al., 1987; see 107271.)
Bierer, B. E., Nishimura, Y., Burakoff, S. J., Smith, B. R. Phenotypic and functional characterization of human cytolytic T cells lacking expression of CD5. J. Clin. Invest. 81: 1390-1397, 1988. [PubMed: 2452832] [Full Text: https://doi.org/10.1172/JCI113468]
Gershon, R. K. Personal Communication. New Haven, Conn. 12/4/1978.
Hecht, B. K., Kipps, T., Johnston, N. K., Cannizzaro, L. A. Leu 1 (CD5) cell surface antigen mapped to 11q13 by in situ hybridization. (Abstract) Cytogenet. Cell Genet. 51: 1012 only, 1989.
Jones, N. H., Clabby, M. L., Dialynas, D. P., Huang, H.-J. S., Herzenberg, L. A., Strominger, J. L. Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1. Nature 323: 346-349, 1986. [PubMed: 3093892] [Full Text: https://doi.org/10.1038/323346a0]
LeClair, K. P., Rabin, M., Nesbitt, M. N., Pravtcheva, D., Ruddle, F. H., Palfree, R. G. E., Bothwell, A. Murine Ly-6 multigene family is located on chromosome 15. Proc. Nat. Acad. Sci. 84: 1638-1642, 1987. [PubMed: 2882510] [Full Text: https://doi.org/10.1073/pnas.84.6.1638]
Lundell, A.-C., Johansen, S., Adlerberth, I., Wold, A. E., Hesselmar, B., Rudin, A. High proportion of CD5+ B cells in infants predicts development of allergic disease. J. Immun. 193: 510-518, 2014. [PubMed: 24928995] [Full Text: https://doi.org/10.4049/jimmunol.1302990]
Ravetch, J. V., Lanier, L. L. Immune inhibitory receptors. Science 290: 84-89, 2000. [PubMed: 11021804] [Full Text: https://doi.org/10.1126/science.290.5489.84]
van Dongen, J. J. M., Wolvers-Tettero, I. L. M., Versnel, M. A., Westerveld, A., Geurts van Kessel, A. H. M. Assignment of the genes coding for the T-cell antigens CD7 (Tp41), CD5 (T1) and CD4 (T4) to human chromosome 17, 11, 12 respectively. (Abstract) Cytogenet. Cell Genet. 40: 767 only, 1985.
Zhang, C., Xin, H., Zhang, W., Yazaki, P. J., Zhang, Z., Le, K., Li, W., Lee, H., Kwak, L., Forman, S., Jove, R., Yu, H. CD5 binds to interleukin-6 and induces a feed-forward loop with the transcription factor STAT3 in B cells to promote cancer. Immunity 44: 913-923, 2016. [PubMed: 27096320] [Full Text: https://doi.org/10.1016/j.immuni.2016.04.003]