T-cell surface glycoprotein CD3 epsilon chain explained

CD3e molecule, epsilon also known as CD3E is a polypeptide which in humans is encoded by the CD3E gene which resides on chromosome 11.^{[1] [2]}

Function

The protein encoded by this gene is the CD3-epsilon polypeptide, which together with CD3-gamma, -delta and -zeta, and the T-cell receptor alpha/beta and gamma/delta heterodimers, forms the T cell receptor-CD3 complex. This complex plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. The genes encoding the epsilon, gamma and delta polypeptides are located in the same cluster on chromosome 11. The epsilon polypeptide plays an essential role in T-cell development.^[3]

Clinical significance

Defects in this gene cause severe immunodeficiency.^{[4] [5]} This gene has also been linked to a susceptibility to type I diabetes in women.^[6]

Interactions

T-cell surface glycoprotein CD3 epsilon chain has been shown to interact with TOP2B,^[7] CD3EAP^[8] and NCK2.^[9]

See also

• CD3 (immunology)
• Cluster of differentiation

References

Further reading

• Li CJ . Therapeutic biology: checkpoint pathway activation therapy, HIV Tat, and transkingdom RNA interference . Journal of Cellular Physiology . 209 . 3 . 695–700 . December 2006 . 17001685 . 10.1002/jcp.20817 . 37846031 .
• Thoenes G, Soudais C, le Deist F, Griscelli C, Fischer A, Lisowska-Grospierre B . Structural analysis of low TCR-CD3 complex expression in T cells of an immunodeficient patient . The Journal of Biological Chemistry . 267 . 1 . 487–93 . January 1992 . 10.1016/S0021-9258(18)48521-3 . 1370449 . free .
• Luzzati AL, Giacomini E, Giordani L, Pugliese O, Viora M, Chersi A . The antigen-specific induction of normal human lymphocytes in vitro is down-regulated by a conserved HIV p24 epitope . Immunology Letters . 33 . 3 . 307–14 . August 1992 . 1385321 . 10.1016/0165-2478(92)90078-3 .
• Lanier LL, Chang C, Spits H, Phillips JH . Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes . Journal of Immunology . 149 . 6 . 1876–80 . September 1992 . 10.4049/jimmunol.149.6.1876 . 1387664 . free .
• Wong S, Moore S, Orisio S, Millward A, Demaine AG . Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11 . Clinical and Experimental Immunology . 83 . 1 . 69–73 . January 1991 . 1671006 . 1535466 . 10.1111/j.1365-2249.1991.tb05590.x .
• Ruegg CL, Strand M . A synthetic peptide with sequence identity to the transmembrane protein GP41 of HIV-1 inhibits distinct lymphocyte activation pathways dependent on protein kinase C and intracellular calcium influx . Cellular Immunology . 137 . 1 . 1–13 . October 1991 . 1832084 . 10.1016/0008-8749(91)90051-C . free .
• Cefai D, Debre P, Kaczorek M, Idziorek T, Autran B, Bismuth G . Human immunodeficiency virus-1 glycoproteins gp120 and gp160 specifically inhibit the CD3/T cell-antigen receptor phosphoinositide transduction pathway . The Journal of Clinical Investigation . 86 . 6 . 2117–24 . December 1990 . 1979339 . 329852 . 10.1172/JCI114950 .
• Luzzati AL, Pugliese O, Giacomini E, Giordani L, Quintieri F, Hraba T, Mach O, Krchnák V, Vágner J . Immunoregulatory effect of a synthetic peptide corresponding to a region of protein p24 of HIV . Folia Biologica . 36 . 1 . 71–7 . 1990 . 2111780 .
• Koning F, Maloy WL, Coligan JE . The implications of subunit interactions for the structure of the T cell receptor-CD3 complex . European Journal of Immunology . 20 . 2 . 299–305 . February 1990 . 2138083 . 10.1002/eji.1830200211 . 2180901 .
• van den Elsen P, Shepley BA, Cho M, Terhorst C . Isolation and characterization of a cDNA clone encoding the murine homologue of the human 20K T3/T-cell receptor glycoprotein . Nature . 314 . 6011 . 542–4 . 1985 . 2859526 . 10.1038/314542a0 . 1985Natur.314..542V . 4321989 .
• Gold DP, Puck JM, Pettey CL, Cho M, Coligan J, Woody JN, Terhorst C . Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex . Nature . 321 . 6068 . 431–4 . 1986 . 3012357 . 10.1038/321431a0 . 1986Natur.321..431G . 4318166 .
• Clevers HC, Dunlap S, Wileman TE, Terhorst C . Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter . Proceedings of the National Academy of Sciences of the United States of America . 85 . 21 . 8156–60 . November 1988 . 3267235 . 282386 . 10.1073/pnas.85.21.8156 . free .
• Gold DP, Clevers H, Alarcon B, Dunlap S, Novotny J, Williams AF, Terhorst C . Evolutionary relationship between the T3 chains of the T-cell receptor complex and the immunoglobulin supergene family . Proceedings of the National Academy of Sciences of the United States of America . 84 . 21 . 7649–53 . November 1987 . 3478717 . 299357 . 10.1073/pnas.84.21.7649 . 1987PNAS...84.7649G . free .
• DeNofrio D, Radcliff G, Weinhold KJ, Denning SM . CD3 delta and epsilon gene expression in CD3-CD16+ natural killer cell clones derived from thymic precursors . Human Immunology . 43 . 4 . 283–94 . August 1995 . 7499176 . 10.1016/0198-8859(95)91034-U .
• Kishimoto H, Kubo RT, Yorifuji H, Nakayama T, Asano Y, Tada T . Physical dissociation of the TCR-CD3 complex accompanies receptor ligation . The Journal of Experimental Medicine . 182 . 6 . 1997–2006 . December 1995 . 7500045 . 2192252 . 10.1084/jem.182.6.1997 .
• Oravecz T, Norcross MA . Costimulatory properties of the human CD4 molecule: enhancement of CD3-induced T cell activation by human immunodeficiency virus type 1 through viral envelope glycoprotein gp120 . AIDS Research and Human Retroviruses . 9 . 10 . 945–55 . October 1993 . 7506554 . 10.1089/aid.1993.9.945 .
• Beecher MS, Baiocchi RA, Linett ML, Krajewski CA, Caligiuri MA . Expression of the zeta protein subunit in CD3- NK effectors derived from human thymus . Cellular Immunology . 155 . 2 . 508–16 . May 1994 . 7514106 . 10.1006/cimm.1994.1143 .
• Luzzati AL, Giacomini E, Giordani L, Viora M, Chersi A, Camponeschi B, Pugliese O . An HIV p24 heptapeptide down-regulates antigen-specific responses in vitro interfering at the level of the T3-Ti complex . Cellular Immunology . 156 . 2 . 286–95 . July 1994 . 7517794 . 10.1006/cimm.1994.1175 .
• Dianzani U, Bragardo M, Buonfiglio D, Redoglia V, Funaro A, Portoles P, Rojo J, Malavasi F, Pileri A . Modulation of CD4 lateral interaction with lymphocyte surface molecules induced by HIV-1 gp120 . European Journal of Immunology . 25 . 5 . 1306–11 . May 1995 . 7539755 . 10.1002/eji.1830250526 . 37717142 .
• Müller B, Cooper L, Terhorst C . Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29) . Immunology Letters . 44 . 2–3 . 97–103 . January 1995 . 7541024 . 10.1016/0165-2478(94)00199-2 .

Notes and References

1. Gold DP, Puck JM, Pettey CL, Cho M, Coligan J, Woody JN, Terhorst C . Isolation of cDNA clones encoding the 20K non-glycosylated polypeptide chain of the human T-cell receptor/T3 complex . Nature . 321 . 6068 . 431–4 . 1986 . 3012357 . 10.1038/321431a0 . 1986Natur.321..431G . 4318166 .
2. Clevers HC, Dunlap S, Wileman TE, Terhorst C . Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter . Proceedings of the National Academy of Sciences of the United States of America . 85 . 21 . 8156–60 . November 1988 . 3267235 . 282386 . 10.1073/pnas.85.21.8156 . free .
3. Web site: Entrez Gene: CD3E CD3e molecule, epsilon (CD3-TCR complex).
4. Soudais C, de Villartay JP, Le Deist F, Fischer A, Lisowska-Grospierre B . Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency . Nature Genetics . 3 . 1 . 77–81 . January 1993 . 8490660 . 10.1038/ng0193-77 . 205341366 .
5. de Saint Basile G, Geissmann F, Flori E, Uring-Lambert B, Soudais C, Cavazzana-Calvo M, Durandy A, Jabado N, Fischer A, Le Deist F . Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3 . The Journal of Clinical Investigation . 114 . 10 . 1512–7 . November 2004 . 15546002 . 525745 . 10.1172/JCI22588 .
6. Wong S, Moore S, Orisio S, Millward A, Demaine AG . Susceptibility to type I diabetes in women is associated with the CD3 epsilon locus on chromosome 11 . Clinical and Experimental Immunology . 83 . 1 . 69–73 . January 1991 . 1671006 . 1535466 . 10.1111/j.1365-2249.1991.tb05590.x .
7. Nakano H, Yamazaki T, Miyatake S, Nozaki N, Kikuchi A, Saito T . Specific interaction of topoisomerase II beta and the CD3 epsilon chain of the T cell receptor complex . The Journal of Biological Chemistry . 271 . 11 . 6483–9 . March 1996 . 8626450 . 10.1074/jbc.271.11.6483 . free .
8. Yamazaki T, Hamano Y, Tashiro H, Itoh K, Nakano H, Miyatake S, Saito T . CAST, a novel CD3epsilon-binding protein transducing activation signal for interleukin-2 production in T cells . The Journal of Biological Chemistry . 274 . 26 . 18173–80 . June 1999 . 10373416 . 10.1074/jbc.274.26.18173 . free .
9. Gil D, Schamel WW, Montoya M, Sánchez-Madrid F, Alarcón B . Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation . Cell . 109 . 7 . 901–12 . June 2002 . 12110186 . 10.1016/S0092-8674(02)00799-7 . 2714623 . free .