CD8A explained

T-cell surface glycoprotein CD8 alpha chain (Cluster of Differentiation 8a), is a protein encoded by CD8A gene.^[1]

Function

The CD8 protein is a cell surface glycoprotein found on most cytotoxic T lymphocytes that mediates efficient cell-cell interactions within the immune system. The CD8, acting as a coreceptor, and the T-cell receptor on the T lymphocyte recognize antigen displayed by an antigen-presenting cell (APC) in the context of class I MHC molecules. The functional coreceptor is either a homodimer composed of two alpha chains, or a heterodimer composed of one alpha and one beta chain. Both alpha and beta chains share significant homology to variable domain of immunoglobulin light chains. This gene encodes the CD8 alpha chain isoforms. Two alternative transcripts encoding distinct isoforms, one membrane associated and one secreted, have been identified.^[1]

Interactions

CD8A has been shown to interact with:

• CD3D,^[2]
• HLA-A,^[3] and
• HLA-G.^{[4] [5]}

See also

• Cluster of differentiation

Further reading

• Book: Parnes JR . Molecular Biology and Function of CD4 and CD8 . Advances in Immunology . 44 . 265–311 . 1989 . 2493728 . 10.1016/S0065-2776(08)60644-6 . 9780120224449 .
• Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY . Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. . Cell Res. . 15 . 11–12 . 923–34 . 2006 . 16354571 . 10.1038/sj.cr.7290370 . free .
• Stove V, Verhasselt B . Modelling thymic HIV-1 Nef effects . Curr. HIV Res. . 4 . 1 . 57–64 . 2006 . 16454711 . 10.2174/157016206775197583 .
• Nakayama K, 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. Immunol. . 148 . 6 . 1919–27 . 1992 . 10.4049/jimmunol.148.6.1919 . 1541829 . 8993127 . free .
• Leahy DJ, Axel R, Hendrickson WA . Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6 A resolution . Cell . 68 . 6 . 1145–62 . 1992 . 1547508 . 10.1016/0092-8674(92)90085-Q . 6261613 .
• Erickson JD, Trojanowski JQ, Eiden LE . Regional distribution and partial molecular characterization of CD4-related mRNA in human brain and peripheral tissues . Brain Res. Mol. Brain Res. . 10 . 1 . 23–31 . 1991 . 1676132 . 10.1016/0169-328X(91)90052-Y .
• Moebius U, Kober G, Griscelli AL, Hercend T, Meuer SC . Expression of different CD8 isoforms on distinct human lymphocyte subpopulations . Eur. J. Immunol. . 21 . 8 . 1793–800 . 1991 . 1831127 . 10.1002/eji.1830210803 . 46227655 .
• Mittler RS, Rankin BM, Kiener PA . Physical associations between CD45 and CD4 or CD8 occur as late activation events in antigen receptor-stimulated human T cells . J. Immunol. . 147 . 10 . 3434–40 . 1991 . 10.4049/jimmunol.147.10.3434 . 1834739 . 21291442 .
• Sanders SK, Giblin PA, Kavathas P . Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts . J. Exp. Med. . 174 . 3 . 737–40 . 1991 . 1908512 . 2118947 . 10.1084/jem.174.3.737 .
• Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE . The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex . Proc. Natl. Acad. Sci. U.S.A. . 86 . 9 . 3277–81 . 1989 . 2470098 . 287114 . 10.1073/pnas.86.9.3277 . 1989PNAS...86.3277B . free .
• Norment AM, Lonberg N, Lacy E, Littman DR . Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 alpha gene . J. Immunol. . 142 . 9 . 3312–9 . 1989 . 10.4049/jimmunol.142.9.3312 . 2496167 . 23835202 . free .
• Nakayama K, Tokito S, Okumura K, Nakauchi H . Structure and expression of the gene encoding CD8 alpha chain (Leu-2/T8) . Immunogenetics . 30 . 5 . 393–7 . 1989 . 2509342 . 10.1007/BF02425282 . 42149394 .
• Giblin P, Ledbetter JA, Kavathas P . A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing . Proc. Natl. Acad. Sci. U.S.A. . 86 . 3 . 998–1002 . 1989 . 2536941 . 286608 . 10.1073/pnas.86.3.998 . 1989PNAS...86..998G . free .
• Aruffo A, Seed B . Expression of cDNA clones encoding the thymocyte antigens CD1a, b, c demonstrates a hierarchy of exclusion in fibroblasts . J. Immunol. . 143 . 5 . 1723–30 . 1989 . 10.4049/jimmunol.143.5.1723 . 2701945 . 23168239 . free .
• Bowcock AM, Kavathas P, Margolskee RF, Herzenberg L, Cavalli-Sforza LL . An RFLP associated with pcDLeu2-14, a human T-cell differentiation antigen CD8 (Leu2) cDNA mapped to 2p12 . Nucleic Acids Res. . 14 . 19 . 7817 . 1986 . 2877435 . 311807 . 10.1093/nar/14.19.7817 .
• Norment AM, Littman DR . A second subunit of CD8 is expressed in human T cells . EMBO J. . 7 . 11 . 3433–9 . 1989 . 3145195 . 454842 . 10.1002/j.1460-2075.1988.tb03217.x.
• Littman DR, Thomas Y, Maddon PJ, Chess L, Axel R . The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes . Cell . 40 . 2 . 237–46 . 1985 . 3871356 . 10.1016/0092-8674(85)90138-2 . 35066139 .
• Sukhatme VP, Sizer KC, Vollmer AC, Hunkapiller T, Parnes JR . The T cell differentiation antigen Leu-2/T8 is homologous to immunoglobulin and T cell receptor variable regions . Cell . 40 . 3 . 591–7 . 1985 . 3918796 . 10.1016/0092-8674(85)90207-7 . 22206011 .
• Parnes JR, Sizer KC, Sukhatme VP, Hunkapiller T . Structure of Leu-2/T8 as deduced from the sequence of a cDNA clone . Behring Inst. Mitt. . 77 . 48–55 . 1986 . 3936473 .

Notes and References

1. Web site: Entrez Gene: CD8A CD8a molecule.
2. Doucey MA, Goffin L, Naeher D, Michielin O, Baumgärtner P, Guillaume P, Palmer E, Luescher IF . CD3 delta establishes a functional link between the T cell receptor and CD8 . J. Biol. Chem. . 278 . 5 . 3257–64 . January 2003 . 12215456 . 10.1074/jbc.M208119200 . free .
3. Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK . Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2 . Nature . 387 . 6633 . 630–4 . June 1997 . 9177355 . 10.1038/42523 . 1997Natur.387..630G . 4267617 .
4. Gao GF, Willcox BE, Wyer JR, Boulter JM, O'Callaghan CA, Maenaka K, Stuart DI, Jones EY, Van Der Merwe PA, Bell JI, Jakobsen BK . Classical and nonclassical class I major histocompatibility complex molecules exhibit subtle conformational differences that affect binding to CD8alphaalpha . J. Biol. Chem. . 275 . 20 . 15232–8 . May 2000 . 10809759 . 10.1074/jbc.275.20.15232. free .
5. Sanders SK, Giblin PA, Kavathas P . Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts . J. Exp. Med. . 174 . 3 . 737–40 . September 1991 . 1908512 . 2118947 . 10.1084/jem.174.3.737.