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CD3ζ

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Synonyms

ζ; CD247; TCRζ

Introduction

CD3ζ is a homodimer-forming type 1 transmembrane (TM) protein and is part of the T cell antigen receptor (TCR) complex along with TCRαβ, CD3γε, and CD3δε dimers expressed on the surface of T cells (Figs. 1 and 2). T cells are an important component of the vertebrate adaptive immune system that are activated via TCR by the peptides generated from infectious agents and presented on major histocompatibility complex (MHC) molecules on the surface of cells. CD3ζ possesses a small extracellular part, a TM region, and a long cytoplasmic part that contains three immunoreceptor tyrosine-based activation motifs (ITAMs), which correspond to the six tyrosines that get phosphorylated upon antigen binding to the extracellular part of TCRαβ. Phosphorylation subsequently activates several downstream signaling cascades. Hence, CD3ζ plays a vital role in the activation of a T cell. CD3ζ is also part of the pre-TCR in pre-T cells and the γδTCR in γδ T cells that...

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CD3ζ, Fig. 1
CD3ζ, Fig. 2
CD3ζ, Fig. 3
CD3ζ, Fig. 4
CD3ζ, Fig. 5

References

  • Aivazian D, Stern LJ. Phosphorylation of T cell receptor zeta is regulated by a lipid dependent folding transition. Nat Struct Biol. 2000;7(11):1023–6.

    PubMed  CrossRef  CAS  Google Scholar 

  • Baniyash M. TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol. 2004;4(9):675–87.

    PubMed  CrossRef  CAS  Google Scholar 

  • Borroto A, Abia D, et al. Crammed signaling motifs in the T-cell receptor. Immunol Lett. 2014;161(1):113–7.

    PubMed  CrossRef  CAS  Google Scholar 

  • Call ME, Schnell JR, et al. The structure of the zetazeta transmembrane dimer reveals features essential for its assembly with the T cell receptor. Cell. 2006;127(2):355–68.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Curnow SJ, Boyer C, et al. TCR-associated zeta-Fc epsilon RI gamma heterodimers on CD4-CD8- NK1.1+ T cells selected by specific class I MHC antigen. Immunity. 1995;3(4):427–38.

    PubMed  CrossRef  CAS  Google Scholar 

  • Dai H, Wang Y, et al. Chimeric antigen receptors modified T-cells for cancer therapy. J Natl Cancer Inst. 2016;108(7). https://doi.org/10.1093/jnci/djv439.

  • Delgado P, Cubelos B, Calleja E, Martínez-Martín N, Ciprés A, Mérida I, Bellas C, Bustelo XR, Alarcón B. Essential function for the GTPase TC21 in homeostatic antigen receptor signaling. Nat Immunol. 2009;10(8):880–8.

    PubMed  CrossRef  CAS  Google Scholar 

  • Deng GM, Beltran J, et al. T cell CD3ζ deficiency enables multiorgan tissue inflammation. J Immunol. 2013;191(7):3563–7.

    PubMed  CrossRef  CAS  Google Scholar 

  • D’Oro U, Munitic I, Chacko G, Karpova T, McNally J, Ashwell JD. Regulation of constitutive TCR internalization by the zeta-chain. J Immunol. 2002;169(11):6269–78.

    PubMed  CrossRef  Google Scholar 

  • Eleftheriadis T, Kartsios C, et al. Chronic inflammation and CD16+ natural killer cell zeta-chain downregulation in hemodialysis patients. Blood Purif. 2008;26(4):317–21.

    PubMed  CrossRef  CAS  Google Scholar 

  • Fernández-Arenas E, Calleja E, Martínez-Martín N, Gharbi SI, Navajas R, García-Medel N, Penela P, Alcamí A, Mayor F Jr, Albar JP, Alarcón B. β-Arrestin-1 mediates the TCR-triggered re-routing of distal receptors to the immunological synapse by a PKC-mediated mechanism. EMBO J. 2014 Mar;33(6):559–77.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Gagnon E, Schubert DA, et al. Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain. J Exp Med. 2012;209(13):2423–39.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Hayes SM, Love PE. Distinct structure and signaling potential of the gamma delta TCR complex. Immunity. 2002;16(6):827–38.

    PubMed  CrossRef  CAS  Google Scholar 

  • Holst J, Wang H, et al. Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nat Immunol. 2008;9(6):658–66.

    PubMed  CrossRef  Google Scholar 

  • Kersh EN, Shaw AS, et al. Fidelity of T cell activation through multistep T cell receptor zeta phosphorylation. Science. 1998;281(5376):572–5.

    PubMed  CrossRef  CAS  Google Scholar 

  • Lanier LL, Yu G, et al. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989;342(6251):803–5.

    PubMed  CrossRef  CAS  Google Scholar 

  • Lee MS, Glassman CR, et al. A mechanical switch couples T cell receptor triggering to the cytoplasmic juxtamembrane regions of CD3ζζ. Immunity. 2015;43(2):227–39.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Louveau A, Angibaud J, et al. Impaired spatial memory in mice lacking CD3ζ is associated with altered NMDA and AMPA receptors signaling independent of T-cell deficiency. J Neurosci. 2013;33(47):18672–85.

    PubMed  CrossRef  CAS  PubMed Central  Google Scholar 

  • Malissen B. An evolutionary and structural perspective on T cell antigen receptor function. Immunol Rev. 2003;191:7–191.

    PubMed  CrossRef  CAS  Google Scholar 

  • Malissen M, Gillet A, et al. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 1993;12(11):4347–55.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Martín-Cófreces NB, Baixauli F, López MJ, Gil D, Monjas A, Alarcón B, Sánchez-Madrid F. End-binding protein 1 controls signal propagation from the T cell receptor. EMBO J. 2012 Nov;31(21):4140–52.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Minguet S, Schamel WWA. A permissive geometry model for TCR-CD3 activation. Trends Biochem Sci. 2008;33(2):51–7.

    PubMed  CrossRef  CAS  Google Scholar 

  • Minguet S, Swamy M, et al. The short length of the extracellular domain of zeta is crucial for T cell antigen receptor function. Immunol Lett. 2008;116(2):195–202.

    PubMed  CrossRef  CAS  Google Scholar 

  • Molnár E, Swamy M, et al. Cholesterol and sphingomyelin drive ligand-independent T-cell antigen receptor nanoclustering. J Biol Chem. 2012;287(51):42664–74.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Nambiar MP, Enyedy EJ, et al. Polymorphisms/mutations of TCR-zeta-chain promoter and 3′ untranslated region and selective expression of TCR zeta-chain with an alternatively spliced 3′ untranslated region in patients with systemic lupus erythematosus. J Autoimmun. 2001;16(2):133–42.

    PubMed  CrossRef  CAS  Google Scholar 

  • Ohno H, Saito T. CD3 zeta and eta chains are produced by alternative splicing from a common gene. Int Immunol. 1990;2(11):1117–9.

    PubMed  CrossRef  CAS  Google Scholar 

  • Ohno H, Aoe T, et al. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. EMBO J. 1993;12(11):4357–66.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Pitcher LA, Mathis MA, et al. Selective expression of the 21-kilodalton tyrosine-phosphorylated form of TCR zeta promotes the emergence of T cells with autoreactive potential. J Immunol. 2005a;174(10):6071–9.

    PubMed  CrossRef  CAS  Google Scholar 

  • Pitcher LA, Mathis MA, et al. The CD3 gamma epsilon/delta epsilon signaling module provides normal T cell functions in the absence of the TCR zeta immunoreceptor tyrosine-based activation motifs. Eur J Immunol. 2005b;35(12):3643–54.

    PubMed  CrossRef  CAS  Google Scholar 

  • Proust R, Bertoglio J, et al. The adaptor protein SAP directly associates with CD3ζ chain and regulates T cell receptor signaling. PLoS One. 2012;7(8):e43200.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Rieux-Laucat F, Hivroz C, et al. Inherited and somatic CD3zeta mutations in a patient with T-cell deficiency. N Engl J Med. 2006;354(18):1913–21.

    PubMed  CrossRef  CAS  Google Scholar 

  • Samelson LE, Harford JB, et al. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985;43(1):223–31.

    PubMed  CrossRef  CAS  Google Scholar 

  • Schamel WW, Alarcón B. Organization of the resting TCR in nanoscale oligomers. Immunol Rev. 2013;251(1):13–20.

    PubMed  CrossRef  CAS  Google Scholar 

  • Schamel WW, Arechaga I, et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J Exp Med. 2005;202(4):493–202.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Shi X, Bi Y, et al. Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids. Nature. 2013;493(7430):111–5.

    PubMed  CrossRef  CAS  Google Scholar 

  • Swamy M, Beck-Garcia K, et al. A cholesterol-based allostery model of T cell receptor phosphorylation. Immunity. 2016;44(5):1091–101.

    PubMed  CrossRef  CAS  Google Scholar 

  • Takeuchi T, Suzuki K. CD247 variants and single-nucleotide polymorphisms observed in systemic lupus erythematosus patients. Rheumatology (Oxford). 2013;52(9):1551–5.

    CrossRef  CAS  Google Scholar 

  • Takeuchi T, Tsuzaka K, et al. TCR zeta chain lacking exon 7 in two patients with systemic lupus erythematosus. Int Immunol. 1998;10(7):911–21.

    PubMed  CrossRef  CAS  Google Scholar 

  • Taylor DD, Sullivan SA, et al. Modulation of T-cell CD3-zeta chain expression during normal pregnancy. J Reprod Immunol. 2002;54(1–2):15–31.

    PubMed  CrossRef  CAS  Google Scholar 

  • van Oers NS, Tohlen B, et al. The 21- and 23-kD forms of TCR zeta are generated by specific ITAM phosphorylations. Nat Immunol. 2000;1(4):322–8.

    PubMed  CrossRef  CAS  Google Scholar 

  • Wang J, Yi L, et al. Lack of association of the CD247 SNP rs2056626 with systemic sclerosis in Han Chinese. Open Rheumatol J. 2014;8:43–5.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  • Xu HP, Chen H, et al. The immune protein CD3zeta is required for normal development of neural circuits in the retina. Neuron. 2010;65(4):503–15.

    PubMed  PubMed Central  CrossRef  CAS  Google Scholar 

  • Yudushkin IA, Vale RD. Imaging T-cell receptor activation reveals accumulation of tyrosine-phosphorylated CD3{zeta} in the endosomal compartment. Proc Natl Acad Sci USA. 2010;107(51):22128–33.

    PubMed  PubMed Central  CrossRef  Google Scholar 

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Correspondence to Wolfgang W. A. Schamel .

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Morath, A., Deswal, S., Schamel, W.W.A. (2018). CD3ζ. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_613

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