Alternative titles; symbols
HGNC Approved Gene Symbol: CD8B
Cytogenetic location: 2p11.2 Genomic coordinates (GRCh38): 2:86,815,369-86,861,886 (from NCBI)
The T-cell differentiation antigen CD8 is a glycoprotein present at the surface of thymocytes and T lymphocytes that recognizes antigenic peptides in the context of the class I major histocompatibility complex (MHC) molecules. In the human, the CD8 antigen is a heterodimeric product of the association of an alpha (CD8A; 186910) and a beta chain (CD8B) (Delarbre et al., 1993).
CD8 is a T-cell glycoprotein expressed only in cytotoxic T cells that recognize antigen in context with class I major histocompatibility antigens. Antibodies against CD8 can block the killing activity of these cells, the inhibition occurring at the level of target cell adhesion. Mouse CD8 consists of 2 distinct chains, Ly-2 (Cd8a) and Ly-3 (Cd8b1); rat CD8, called Ox-8, also has 2 chains. Human CD8 was thought to be made up of only 1 chain in mature T cells. However, Johnson (1987) isolated CD8B, a human gene homologous to the gene encoding the second rodent CD8 chain, and showed that it is transcribed in human thymocytes and in some acute T-cell leukemias.
By analysis of a panel of 14 human-rodent somatic cell hybrids, Spurr et al. (1988) found that CD8B maps to human chromosome 2. In the mouse, the genes that encode the 2 CD8 chains are closely linked on chromosome 6. No recombination was observed in 370 meiotic events. These genes are also closely linked to the immunoglobulin kappa light chain cluster in the mouse. The linkage between CD8A (186910) and the kappa locus is also conserved in man. Close linkage is of interest since these proteins all belong to the immunoglobulin superfamily.
Nakayama et al. (1992) discovered a second but inactive CD8 beta-chain gene, which they named CD8B2, the functional gene being renamed CD8B1. The nucleotide sequences of the coding and noncoding regions of CD8B1 and CD8B2 were found to be 98.9% homologous, suggesting that the duplication event had occurred rather recently in the evolution of the human lineage. They showed that the CD8B pseudogene was present in all human Japanese and Caucasian samples tested. Delarbre et al. (1993) showed that the pseudogene is missing exons 8 and 9 of CD8B. From a study of somatic cell hybrids, they concluded that, like CD8A and CD8B, the pseudogene is located on chromosome 2. Pulsed-field gel electrophoresis experiments demonstrated that the pseudogene is at least 1,500 kb removed from the functional gene, CD8B.
Zhang et al. (1996) demonstrated, by fluorescence in situ hybridization, that the second CD8B gene locus in the human maps to 2q12, a position on the opposite side of the centromere from the first locus.
Delarbre et al. (1993) demonstrated that the duplication of the CD8B gene had taken place in an ancestor common to the human, gorilla, and chimpanzee clade, most likely excluding the orangutan and other primates.
To locate factors regulating the expression of CD8 and the functional commitment of CD8-positive T cells, Kieffer et al. (2002) identified SATB1 (602075)- and GATA3 (131320)-binding sites in matrix attachment regions and DNase I hypersensitive sites at the 3-prime end of the CD8B gene. They proposed that this region is an epigenetic regulator of CD8 expression.
In mice, at least 5 Cd8 cis-acting enhancers, individually or in combination, direct expression in the T-cell lineage, and deletion of specific enhancers leads to variegated expression of Cd8a/Cd8b heterodimers in double-positive thymocytes. Bilic et al. (2006) showed that Cd8 variegation due to enhancer deletion correlated with an epigenetic 'off' state, linking Cd8 enhancer function with chromatin remodeling of Cd8a and Cd8b. The zinc finger protein Mazr (ZNF278; 605165) bound the Cd8 enhancer and, via its N-terminal domain, interacted with the Ncor1 (600849) complex in double-negative thymocytes. Mazr was downregulated in double-positive and Cd8 single-positive thymocytes. Constitutive expression of Mazr during T-cell development resulted in variegated expression of Cd8 in double-positive thymocytes. Bilic et al. (2006) concluded that MAZR is a negative regulator of CD8 expression in double-negative thymocytes.
Bilic, I., Koesters, C., Unger, B., Sekimata, M., Hertweck, A., Maschek, R., Wilson, C. B., Ellmeier, W. Negative regulation of CD8 expression via Cd8 enhancer-mediated recruitment of the zinc finger protein MAZR. Nature Immun. 7: 392-400, 2006. [PubMed: 16491076] [Full Text: https://doi.org/10.1038/ni1311]
Delarbre, C., Nakauchi, H., Bontrop, R., Kourilsky, P., Gachelin, G. Duplication of the CD8 beta-chain gene as a marker of the man-gorilla-chimpanzee clade. Proc. Nat. Acad. Sci. 90: 7049-7053, 1993. [PubMed: 8346216] [Full Text: https://doi.org/10.1073/pnas.90.15.7049]
Johnson, P. A human homolog of the mouse CD8 molecule, Lyt-3: genomic sequence and expression. Immunogenetics 26: 174-177, 1987. [PubMed: 3114136] [Full Text: https://doi.org/10.1007/BF00365908]
Kieffer, L. J., Greally, J. M., Landres, I., Nag, S., Nakajima, Y., Kohwi-Shigematsu, T., Kavathas, P. B. Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3. J. Immun. 168: 3915-3922, 2002. [PubMed: 11937547] [Full Text: https://doi.org/10.4049/jimmunol.168.8.3915]
Nakayama, K. I., Kawachi, Y., Tokito, S., Minami, N., Yamamoto, R., Imai, T., Gachelin, G., Nakauchi, H. Recent duplication of the two human CD8 beta-chain genes. J. Immun. 148: 1919-1927, 1992. [PubMed: 1541829]
Spurr, N. K., Goodfellow, P. N., Johnson, P. CD8B, the human equivalent of the mouse Ly-3 gene is localized on chromosome 2. Immunogenetics 27: 70-72, 1988. [PubMed: 3257101] [Full Text: https://doi.org/10.1007/BF00404448]
Zhang, X.-L., Heng, H. H. Q., Yang, Y., Tsui, L.-C., Parnes, J. R., Chamberlain, J. W. Chromosomal mapping of the second human CD8B gene locus. Immunogenetics 43: 220-226, 1996. [PubMed: 8575821] [Full Text: https://doi.org/10.1007/BF00587303]