Skip to main content
SpringerLink
Log in

T-Cell Receptor

  • Chapter
Multichain Immune Recognition Receptor Signaling

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 640))

Abstract

The T-cell antigen receptor complex (TCR/CD3) is a cell surface structure that defines the T lymphocyte lineage, where it fulfills two basic functions, namely antigen recognition and triggering of signals needed to mount adequate responses to foreign aggression and/or to undergo differentiation. Knowing the precise structure of the complex in terms of its components and their relative arrangement and interactions before and after antigen recognition is essential to understand how ligand binding transforms into functionally relevant T-cell responses. These include not only full responses to foreign peptide antigens by mature T-cells, but also other phenomena like modulation of T-cell activation with altered peptide ligands, positive and negative selection of thymocytes, alloreactivity and autoimmune reactions.

A wealth of new data has accumulated in recent years on the structure of TCR/antigen complexes and CD3 Polypeptides and on the stoichiometry of the TCR/CD3 complex and intersubunit interactions. In this review, we discuss how these data fit into a meaningful model of the TCR/CD3 function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Clevers H, Alarcón B, Wileman T et al. The T-cell receptor/CD3 complex: A dynamic protein ensemble. Ann Rev Immunol 1988; 6:629–662.

    Article  CAS  Google Scholar 

  2. Klausner RD, Lippincott-Schwartz J, Bonifacino JS. The T-cell antigen receptor: Insight into organelle biology. Annu Rev Cell Biol 1990; 6:403–431.

    Article  PubMed  CAS  Google Scholar 

  3. Kuhns MS, Davis MM, Garcia KC et al. Deconstructing the form and function of the TCR/CD3 Complex. Immunity 2006; 24:133–9.

    Article  PubMed  CAS  Google Scholar 

  4. Göbel TWF, Bolliger L. Evolution of the T-cell receptor signal transduction units. Curr Top Microbiol Immunol 2000; 248:303–320.

    PubMed  Google Scholar 

  5. Rudolph MG, Stanfield RL, Wilson IA. How TCRs bind MHCs, peptides and coreceptors. Annu Rev Immunol 2006; 24:419–466.

    Article  PubMed  CAS  Google Scholar 

  6. Call ME, Wucherpfennig KW. The T-cell receptor: Critical role of the membrane environment in receptor assembly and function. Annu Rev Immunol 2005; 23:101–125.

    Article  PubMed  CAS  Google Scholar 

  7. García KC, Degano M, Stanfield RL et al. An αβ T-cell receptor structure at 2.5 Å and its orientation in the TCR-MHC complex. Science 1996; 274:209–219.

    Article  PubMed  Google Scholar 

  8. Alarcón B, Gil D, Delgado P et al. Initiation of TCR signaling: Regulation within CD3 dimers. Immunol Rev 2003; 191:38–46.

    Article  PubMed  Google Scholar 

  9. Gil D, Schamel WWA, Montoya M et al. Recruitment of Nek by CD3ε reveals a ligand-induced conformational change essential for T-cell receptor signaling and synapse formation. Cell 2002; 109:901–912.

    Article  PubMed  CAS  Google Scholar 

  10. Cambier JC. New nomenclature for the Reth motif (or ARH1ARAM/YxxL). Immunol Today 1995; 16:110.

    Article  PubMed  CAS  Google Scholar 

  11. Buferne M, Luton F, Letorneur F et al. Role of CD3δ in surface expression of the TCR/CD3 complex and in activation for killing analyzed with a CD3δ-negative cytotoxic T-lymphocyte variant. J Immunol 1992; 148:657–664.

    PubMed  CAS  Google Scholar 

  12. Dietrich J, Neising A, Hou X et al. Role of CD3y in T-cell receptor assembly. J Cell Biol 1996; 132:299–310.

    Article  PubMed  CAS  Google Scholar 

  13. Luton F, Buferne M, Legendre V et al. Role of CD3y and CD3δ cytoplasmic domains in cytolytic T-lymphocyte functions and TCR/CD3 down-modulation. J Immunol 1997; 158:4162–4170.

    PubMed  CAS  Google Scholar 

  14. Transy C, Moingeon P, Stebbins C et al. Deletion of the cytoplasmic region of the CD3 epsilon subunit does not prevent assembly of a functional T-cell receptor. Proc Natl Acad Sci USA 1989; 86:7108–7112.

    Article  PubMed  CAS  Google Scholar 

  15. Wegener AMK, Letourneur F, Hoeveler A et al. The T-cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell 1992; 68:83–95.

    Article  PubMed  CAS  Google Scholar 

  16. Adams EJ, Chien Y-H, Garcia KC. Structure of a γδ T-cell receptor in complex with the nonclassical MHC T22. Science 2005; 308:227–231.

    Article  PubMed  CAS  Google Scholar 

  17. Alarcón B, Ley SC, Sánchez-Madrid F et al. The CD3-γ and CD3-δ subunits of the T-cell antigen recep-tor can be expressed within distinct functional TCR/CD3 complexes. EMBO J 1991; 10:903–912.

    PubMed  Google Scholar 

  18. Sun ZJ, Kim ST, Kim IC et al. Solution structure of the CD3εδ ectodomain and comparison with CD3εγ as a basis for modeling T-cell receptor topology and signaling. Proc Natl Acad Sci USA 2004; 101:16867–16872.

    Article  PubMed  CAS  Google Scholar 

  19. Sun ZJ, Kim KS, Wagner G et al. Mechanisms contributing to T-cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3εγ heterodimer. Cell 2001; 105:913–923.

    Article  PubMed  CAS  Google Scholar 

  20. Kjer-Nielsen L, Dunstone MA, Kostenko L et al. Crystal structure of the human T-cell receptor CD38Y heterodimer complexed to the therapeutic mAb OKT3. Proc Natl Acad Sci USA 2004; 101:7675–7680.

    Article  PubMed  CAS  Google Scholar 

  21. Arnett KL, Harrison SC, Wiley DC. Crystal structure of a human CD3-ε/δ dimer in complex with a UCHT1 single-chain antibody fragment. Proc Natl Acad Sci USA 2004; 101:16268–16273.

    Article  PubMed  CAS  Google Scholar 

  22. Blumberg RS, Ley S, Sancho J et al. Structure of the T-cell antigen receptor: Evidence for two CD3 ε subunits in the T-cell receptor complex. Proc Natl Acad Sci USA 1990; 87:7220–7224.

    Article  PubMed  CAS  Google Scholar 

  23. de 1a Hera A, Müller U, Olsson C et al. Structure of the T-cell antigen receptor (TCR): Two CD3ε subunits in a functional TCR/CD3 complex. J Exp Med 1991; 173:7–17.

    Article  PubMed  Google Scholar 

  24. Schamel WWA, Arechaga I, Risueno RM et al. Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response. J Exp Med 2005; 202:493–503.

    Article  PubMed  CAS  Google Scholar 

  25. Meuer S, Acuto O, Hussey RE et al. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor. Nature 1983; 303:808–810.

    Article  PubMed  CAS  Google Scholar 

  26. Portolés P, Rojo J, Golby A et al. Monoclonal antibodies to murine CD3µ define distinct epitopes, one of which may interact with CD4 during T-cell activation. J Immunol 1989; 142:4169–4175.

    PubMed  Google Scholar 

  27. Punt JA, Roberts JL, Kearse KP et al. Stoichiometry of the T-cell antigen receptor (TCR) complex: Each TCR/CD3 complex contains one TCR α, one TCR β and two CD3ε chains. J Exp Med 1994; 180:587–593.

    Article  PubMed  CAS  Google Scholar 

  28. Thibault G, Bardos P. Compared TCR and CD3ε expression on αβ and γδ T-cells. Evidence for the association of two TCR heterodimers with three CD3ε chains in the TCR/CD3 complex. J Immunol 1995; 154:3814–3820.

    PubMed  CAS  Google Scholar 

  29. San José E, Sahuquillo AG, Bragado R et al. Assembly of the TCR/CD3 complex: CD3e/δ and CD3ε/γ dimers associate indistinctly with both TCRa and TCRβ chains. Evidence for a double TCR heterodimer model. Eut J Immunol 1998; 28:12–21.

    Article  Google Scholar 

  30. Wang J, Lim K, Smoylar A et al. Atomic structure of an αβ T-cell receptor (TCR) heterodimer in complex with an anti-TCR Fab fragment derived from a mitogenic antibody. EMBO J 1998; 17:10–26.

    Article  PubMed  Google Scholar 

  31. Fernández-Miguel G, Alarcón B, Iglesias A et al. Multivalent structure of an αβ T-cell receptor. Proc Natl Acad Sci USA 1999; 96:1547–1552.

    Article  PubMed  Google Scholar 

  32. Call ME, Pyrdol J, Wiedmann M et al. The organizing principle in the formation of the T-cell recep-tor-CD3 complex. Cell 2002; 111:967–979.

    Article  PubMed  CAS  Google Scholar 

  33. Call M, Pyrdol J, Wucherpfennig K. Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum. EMBO J 2004; 23:2348–2357.

    Article  PubMed  CAS  Google Scholar 

  34. Hellwig S, Schamel WWA, Pflugfelder U et al. Differences in pairing and cluster formation of T-cell receptor α-and β-chains in T-cell clones and fusion hybridomas. Immunobiology 2005; 210:685–694.

    Article  PubMed  CAS  Google Scholar 

  35. Schamel WWA, Risueno RM, Minguet S et al. A conformation-and avidity-based proofreading mechanism for the TCR-CD3 complex. Trends Immunol 2006; 27:176–182.

    Article  PubMed  CAS  Google Scholar 

  36. Cochran JR. Cochran JR, Cameron TO et al. Receptor proximity, not intermolecular orientation, is critical for triggering T-cell activation. J Biol Chem 2001; 276:28068–28074.

    Article  PubMed  CAS  Google Scholar 

  37. Ghendler Y, Smolyar A, Chang H-C et al. One of the CD3ε subunits within a T-cell receptor complex lies in close proximity to the Cβ FG loop. J Exp Med 1998; 187:1529–1536.

    Article  PubMed  CAS  Google Scholar 

  38. Borroto A, Mallabiabarrena A, Albar JP et al. Characterization of the region involved in CD3 pairwise interactions within the T-cell receptor complex. J Biol Chem 1998; 273:12807–12816.

    Article  PubMed  CAS  Google Scholar 

  39. Wegener AMK, Hou X, Dietrich J et al. Distinct domains of the CD3-γ chain are involved in the surface expression and function of the T-cell antigen receptor. J Biol Chem 1995; 270:4675–4680.

    Article  PubMed  CAS  Google Scholar 

  40. Bäckström BT, Milia E, Peter A et al. A motif within the T-cell receptor α chain constant region connecting peptide domain controls antigen responsiveness. Immunity 1996; 5:437–447.

    Article  PubMed  Google Scholar 

  41. Werlen G, Hausmann B, Palmer E. A motif in the αβ T-cell receptor controls positive selection by modulating ERK activity. Nature 2000; 406:422–426.

    Article  PubMed  CAS  Google Scholar 

  42. Brenner MB, Trowbridge IS, Strominger JL. Cross-linking of human T-cell receptor proteins: Association between the T-cell idiotype β subunit and the T3 glycoprotein heavy subunit. Cell 1985; 40:183–190.

    Article  PubMed  CAS  Google Scholar 

  43. Tourna M, Chang H-C, Sasada T et al. The TCR Cβ FG loop regulates αβ T-cell development. J Immunol 2006; 176:6812–6823.

    Google Scholar 

  44. Hayes SM, Laky K, El-Khoury D et al. Activation-induced modification in the CD3 complex of the γδ T-cell receptor. J Exp Med 2002; 196:1355–1361. Erratum in: J. Exp. Med. 196: 1653.

    Article  PubMed  CAS  Google Scholar 

  45. Hayes SM, Love PE. Distinct structure and signaling potential of the γδ TCR complex. Immunity 2002; 16:827–838.

    Article  PubMed  CAS  Google Scholar 

  46. Hayes SM, Love PE. Stoichiometry of the murine γδ T-cell receptor. J Exp Med 2006; 203:47–52.

    Article  PubMed  CAS  Google Scholar 

  47. Dadi HK, Simon AJ, Roifman CM. Effect of CD3δ deficiency on maturation of α/β and γ/δ T-cell lineages in severe combined immunodeficiency. New Eng J Med 2003; 349:1821–1828.

    Article  PubMed  CAS  Google Scholar 

  48. Johansson B, Palmer E, Bolliger L. The extracellular domain of the ζ-chain is essential for TCR function. J Immunol 1999; 162:878–885.

    PubMed  CAS  Google Scholar 

  49. Rodríguez-Tarduchy G, Sahuquillo AG, Alarcón B et al. Apoptosis but not other activation events is inhibited by a mutation in the transmembrane domain of T-cell receptor β that impairs CD3ζ association. J Biol Chem 1996; 271:30417–30425.

    Article  PubMed  Google Scholar 

  50. Teixeiro E, Daniels MA, Hausmann B et al. T-cell division and death are segregated by mutation of TCRβ chain constant domains. Immunity 2004; 21:515–526.

    Article  PubMed  CAS  Google Scholar 

  51. Janeway Jr. CA. The T-cell receptor as a multicomponent signalling machine: CD4/CD8 Coreceptors and CD45 in T-cell activation. Ann Rev Immunol 1992; 10:645–674.

    CAS  Google Scholar 

  52. Gao FG, Tormo J, Gerth UC et al. Crystal structure of the complex between human CD8αα and HLA-A2. Nature 1997; 387:630–634.

    Article  PubMed  CAS  Google Scholar 

  53. Doucey M-A, Goffin L, Naeher D et al. CD3δ establishes a functional link between the T-cell receptor and CD8. J Biol Chem 2003; 278:3257–3264.

    Article  PubMed  CAS  Google Scholar 

  54. Suzuki S, Kupsch J, Eichmann K et al. Biochemical evidence of the physical association of majority of the CD3δ chains with the accessoryreceptor molecules CD4 and CD8 on nonactivated T-lymphocytes. Eur J Immunol 1992; 22:2475–2479.

    Article  PubMed  CAS  Google Scholar 

  55. Wang J, Meijers R, Xiong Y et al. Crystal structure of the human CD4 N-terminal two-domain fragment complexed to a class II MHC molecule. Proc Natl Acad Sci USA 2001; 98:10799–10804.

    Article  PubMed  CAS  Google Scholar 

  56. Wu H, Kwong PD, Hendrickson WA. Dimeric association and segmental variability in the structure of human CD4. Nature 1997; 387:527–530.

    Article  PubMed  CAS  Google Scholar 

  57. Moldovan M-C, Yachou A, Levesque K et al. CD4 dimers constitute the functional component required for T-cell activation. J Immunol 2002; 169:6261–6268.

    PubMed  CAS  Google Scholar 

  58. Maekawa A, Schmidt B, Fazekas de St. Groth B et al. Evidence for a domain-swapped CD4 dimer as the coreceptor for binding to Class II MHC. J Immunol 2006; 176:6873–6878.

    Google Scholar 

  59. Dianzani U, Shaw A, Al-Ramadi BK et al. Physical association of CD4 with the T-cell receptor. J Immunol 1992; 148:678–688.

    PubMed  CAS  Google Scholar 

  60. Saint-Ruf C, Panigada M, Azogi O et al. Different initiation of preTCR and γδTCR signalling. Nature 2000; 406:524–527.

    Article  PubMed  CAS  Google Scholar 

  61. Wilson A, MacDonald HR. Expression of genes encoding the preTCR and CD3 complex during thymus development. Int Immunol 1995; 7:1659–1664.

    Article  PubMed  CAS  Google Scholar 

  62. Rudd PM, Wormald MR, Stanfield RL et al. Roles for glycosylation of cell surface receptors involved in cellular immune recognition. J Mol Biol 1999; 293:351–366.

    Article  PubMed  CAS  Google Scholar 

  63. Zapata DA, Schamel WWA, Torres PS et al. Biochemical differences in the alpha beta TCR-CD3 surface complex between CD8+ and CD4+ human mature T-lymphocytes. J Biol Chem 2004; 279:24485–24492.

    Article  PubMed  CAS  Google Scholar 

  64. Criado G, Feito MJ, Ojeda G et al. Variability of invariant mouse CD3ε chains detected by anti-CD3 antibodies. Eur J Immunol 2000; 30:1469–1479.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centra de Investigaciones Biológicas, CSIC, Ramiro de Maeztu, 9, E-28040, Madrid, Spain

    Jose M. Rojo & Raquel Bello

  2. Centro Nacional de Microbiologóa, Institute de Salud Carlos III, Majadahonda, Madrid, Spain

    Pilar Portolés

Authors
  1. Jose M. Rojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel Bello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pilar Portolés
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pathology, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Alexander B. Sigalov PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Rojo, J.M., Bello, R., Portolés, P. (2008). T-Cell Receptor. In: Sigalov, A.B. (eds) Multichain Immune Recognition Receptor Signaling. Advances in Experimental Medicine and Biology, vol 640. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09789-3_1

Download citation

Publish with us

Policies and ethics

Search

Navigation