CD3e ( English T-cell surface glycoprotein CD3 epsilon chain ) is a transmembrane protein of the CD3 glycoprotein family located on the surface of T-lymphocytes . The product of the human CD3E gene is located on the 11th chromosome [1] [2] .
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Content
- 1 Functions
- 2 Clinical significance
- 3 Interactions
- 4 notes
- 5 Literature
Functions
Part of the TCR-CD3 multimolecular complex on the surface of T-lymphocytes , which plays a key role in acquired immunity . When antigen-presenting cells activate TCR , the signal is transmitted through the membrane by the CD3 receptor complex polypeptide chains: CD3D (δ chain), CD3E (ε chain), CD3G (γ chain) and CD3Z (ζ chain). All these chains contain activating ITAM motifs in their cytoplasmic domains. After receptor activation, ITAM motifs are phosphorylated by tyrosine kinases LCK and FYN of the Src family, which leads to the activation of a further signaling cascade [3] . [4] . In addition, CD3E plays a key role in the normal development of T-lymphocytes . Initiates the assembly of the TCR-CD3 complex, forming heterodimers CD3D / CD3E and CD3G / CD3E. Participates in the internalization of the regulation of the membrane complex through endocytosis , activated by the cytosolic portion of the molecule [5] [6] .
Clinical Importance
Defects of this gene lead to severe immunodeficiency [7] [8] . In addition, the CD3E gene is associated with sensitivity to type 1 diabetes in women [9] .
Interactions
CD3E interacts with the TOP2B protein [10] , CD3EAP [11], and NCK2 . [12] .
Notes
- ↑ 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: journal. - 1986. - Vol. 321 , no. 6068 . - P. 431-434 . - DOI : 10.1038 / 321431a0 . - PMID 3012357 .
- ↑ Clevers HC, Dunlap S., Wileman TE, Terhorst C. Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter (Eng.) // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1988 .-- November ( vol. 85 , no. 21 ). - P. 8156-8160 . - DOI : 10.1073 / pnas.85.21.8156 . - PMID 3267235 .
- ↑ 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. (Eng.) // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1989. - Vol. 86 , no. 9 . - P. 3277-3281 . - DOI : 10.1073 / pnas.86.9.3277 . - PMID 2470098 .
- ↑ Entrez Gene: CD3E CD3e molecule, epsilon (CD3-TCR complex) .
- ↑ Borroto A., Lama J., Niedergang F., Dautry-Varsat A., Alarcón B., Alcover A. The CD3 epsilon subunit of the TCR contains endocytosis signals. (Eng.) // J Immunol : journal. - 1999. - Vol. 163 , no. 1 . - P. 25-31 . - PMID 10384095 .
- ↑ Martin-Blanco N., Jiménez Teja D., Bretones G., Borroto A., Caraballo M., Screpanti I et al. CD3ε recruits Numb to promote TCR degradation. (Eng.) // Int Immunol : journal. - 2016. - Vol. 28 , no. 3 . - P. 127-137 . - DOI : 10.1093 / intimm / dxv060 . - PMID 26507128 .
- ↑ 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 (Eng.) // Nature Genetics : journal. - 1993 .-- January ( vol. 3 , no. 1 ). - P. 77-81 . - DOI : 10.1038 / ng0193-77 . - PMID 8490660 .
- ↑ 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 (Eng.) // The Journal of Clinical Investigation : journal. - 2004 .-- November ( vol. 114 , no. 10 ). - P. 1512-1517 . - DOI : 10.1172 / JCI22588 . - PMID 15546002 .
- ↑ 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 (English) // Clinical and Experimental Immunology : journal. - 1991 .-- January ( vol. 83 , no. 1 ). - P. 69-73 . - DOI : 10.1111 / j.1365-2249.1991.tb05590.x . - PMID 1671006 .
- ↑ 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 (Eng.) // The Journal of Biological Chemistry : journal. - 1996 .-- March ( vol. 271 , no. 11 ). - P. 6483-6489 . - DOI : 10.1074 / jbc.271.11.6483 . - PMID 8626450 .
- ↑ 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 : journal. - 1999 .-- June ( vol. 274 , no. 26 ). - P. 18173-18180 . - DOI : 10.1074 / jbc.274.26.18173 . - PMID 10373416 .
- ↑ 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 (Eng.) // Cell : journal. - Cell Press 2002. June ( vol. 109 , no. 7 ). - P. 901-912 . - DOI : 10.1016 / S0092-8674 (02) 00799-7 . - PMID 12110186 .
Literature
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- 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 (Eng.) // The Journal of Biological Chemistry : journal. - 1992 .-- January ( vol. 267 , no. 1 ). - P. 487-493 . - PMID 1370449 .
- 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 (Eng.) // Immunology Letters : journal. - 1992 .-- August ( vol. 33 , no. 3 ). - P. 307-314 . - DOI : 10.1016 / 0165-2478 (92) 90078-3 . - PMID 1385321 .
- 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 (English) // Journal of Immunology : journal. - 1992 .-- September ( vol. 149 , no. 6 ). - P. 1876-1880 . - PMID 1387664 .
- 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 (English) // Clinical and Experimental Immunology : journal. - 1991 .-- January ( vol. 83 , no. 1 ). - P. 69-73 . - DOI : 10.1111 / j.1365-2249.1991.tb05590.x . - PMID 1671006 .
- 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 (English) // Cellular Immunology: journal. - 1991 .-- October ( vol. 137 , no. 1 ). - P. 1-13 . - DOI : 10.1016 / 0008-8749 (91) 90051-C . - PMID 1832084 .
- 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 (English) / / The Journal of Clinical Investigation : journal. - 1990 .-- December ( vol. 86 , no. 6 ). - P. 2117-2124 . - DOI : 10.1172 / JCI114950 . - PMID 1979339 .
- 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 ( English) // Folia Biologica: journal. - 1990. - Vol. 36 , no. 1 . - P. 71-7 . - PMID 2111780 .
- Koning F., Maloy WL, Coligan JE The implications of subunit interactions for the structure of the T cell receptor-CD3 complex (Eng.) // European Journal of Immunology : journal. - 1990 .-- February ( vol. 20 , no. 2 ). - P. 299-305 . - DOI : 10.1002 / eji.1830200211 . - PMID 2138083 .
- 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 (Eng.) // Nature: journal. - 1985. - Vol. 314 , no. 6011 - P. 542-544 . - DOI : 10.1038 / 314542a0 . - PMID 2859526 .
- 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: journal. - 1986. - Vol. 321 , no. 6068 . - P. 431-434 . - DOI : 10.1038 / 321431a0 . - PMID 3012357 .
- Clevers HC, Dunlap S., Wileman TE, Terhorst C. Human CD3-epsilon gene contains three miniexons and is transcribed from a non-TATA promoter (Eng.) // Proceedings of the National Academy of Sciences of the United States of America : journal. - 1988 .-- November ( vol. 85 , no. 21 ). - P. 8156-8160 . - DOI : 10.1073 / pnas.85.21.8156 . - PMID 3267235 .
- 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 : journal. - 1987. - November ( vol. 84 , no. 21 ). - P. 7649-7653 . - DOI : 10.1073 / pnas.84.21.7649 . - PMID 3478717 .
- 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 (Eng.) // Human Immunology : journal. - 1995 .-- August ( vol. 43 , no. 4 ). - P. 283-294 . - DOI : 10.1016 / 0198-8859 (95) 91034-U . - PMID 7499176 .
- Kishimoto H., Kubo RT, Yorifuji H., Nakayama T., Asano Y., Tada T. Physical dissociation of the TCR-CD3 complex accompanies receptor ligation (Eng.) // The Journal of Experimental Medicine : journal. - Rockefeller University Press 1995 .-- December ( vol. 182 , no. 6 ). - P. 1997-2006 . - DOI : 10.1084 / jem.182.6.1997 . - PMID 7500045 .
- 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 (Eng.) // AIDS Research and Human Retroviruses : journal. - 1993 .-- October ( vol. 9 , no. 10 ). - P. 945-955 . - DOI : 10.1089 / aid . 1993.9.945 . - PMID 7506554 .
- Beecher MS, Baiocchi RA, Linett ML, Krajewski CA, Caligiuri MA Expression of the zeta protein subunit in CD3- NK effectors derived from human thymus (English) // Cellular Immunology: journal. - 1994 .-- May ( vol. 155 , no. 2 ). - P. 508-516 . - DOI : 10.1006 / cimm.1994.1143 . - PMID 7514106 .
- 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 ( English) // Cellular Immunology: journal. - 1994 .-- July ( vol. 156 , no. 2 ). - P. 286-295 . - DOI : 10.1006 / cimm.1994.1175 . - PMID 7517794 .
- 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 (English) // European Journal of Immunology : journal. - 1995 .-- May ( vol. 25 , no. 5 ). - P. 1306-1311 . - DOI : 10.1002 / eji.1830250526 . - PMID 7539755 .
- Müller B., Cooper L., Terhorst C. Interplay between the human TCR / CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29) (Eng.) // Immunology Letters : journal. - 1995. - January ( vol. 44 , no. 2-3 ). - P. 97-103 . - DOI : 10.1016 / 0165-2478 (94) 00199-2 . - PMID 7541024 .