Home LiteratureArticle Details
PMID: 15152191 Published · ppublish English Journal Article

Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum.

The EMBO journal ·Vol. 23 ·No. 12 ·2004-06-16 ·Pages 2348-57

Call ME, Pyrdol J, Wucherpfennig KW

Abstract

The T-cell receptor (TCR)-CD3 complex is critical for T-cell development and function, and represents one of the most complex transmembrane receptors. Models of different stoichiometry and valency have been proposed based on cellular experiments and these have important implications for the mechanisms of receptor triggering. Since determination of receptor stoichiometry in T-cells is not possible due to the presence of previously synthesized, unlabeled receptor components with different half-lives, we examined the stoichiometry of the receptor assembled in endoplasmic reticulum (ER) microsomes of B-cell origin. The stoichiometric relationship among all subunits was directly determined using intact radiolabeled TCR-CD3 complexes that were isolated with a sequential, non-denaturing immunoprecipitation method, and identical results were obtained with two detergents belonging to different structural classes. The results firmly establish that the alphabeta TCR-CD3 complex assembled in the ER is monovalent and composed of one copy of the TCRalphabeta, CD3deltaepsilon, CD3gammaepsilon and zeta-zeta dimers.

MeSH Terms
Amino Acid Sequence CD3 Complex/metabolism Endoplasmic Reticulum/metabolism Molecular Sequence Data Precipitin Tests Receptors, Antigen, T-Cell/metabolism
Chemicals
CD3 Complex Receptors, Antigen, T-Cell
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Call Matthew E
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Pyrdol Jason
Wucherpfennig Kai W
References (43)
43 references, click to expand
  1. Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.
    EMBO J. 2000 Nov 1;19(21):5611-24 PMID: 11060013
  2. Requirements for cell surface expression of the human TCR/CD3 complex in non-T cells.
    Int Immunol. 1991 Apr;3(4):359-68 PMID: 1831654
  3. The immunological synapse.
    Annu Rev Immunol. 2001;19:375-96 PMID: 11244041
  4. The use of mRNA display to select high-affinity protein-binding peptides.
    Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):3750-5 PMID: 11274392
  5. Mechanisms contributing to T cell receptor signaling and assembly revealed by the solution structure of an ectodomain fragment of the CD3 epsilon gamma heterodimer.
    Cell. 2001 Jun 29;105(7):913-23 PMID: 11439187
  6. Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone.
    Science. 2001 Aug 31;293(5535):1657-62 PMID: 11533490
  7. The organizing principle in the formation of the T cell receptor-CD3 complex.
    Cell. 2002 Dec 27;111(7):967-79 PMID: 12507424
  8. Electrostatic fasteners hold the T cell receptor-CD3 complex together.
    Mol Cell. 2003 Jan;11(1):5-6 PMID: 12535514
  9. Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin.
    Nature. 1982 Nov 4;300(5887):66-9 PMID: 6982419
  10. Cross-linking of human T cell receptor proteins: association between the T cell idiotype beta subunit and the T3 glycoprotein heavy subunit.
    Cell. 1985 Jan;40(1):183-90 PMID: 3871355
  11. Assembly of the human T cell receptor-CD3 complex takes place in the endoplasmic reticulum and involves intermediary complexes between the CD3-gamma.delta.epsilon core and single T cell receptor alpha or beta chains.
    J Biol Chem. 1988 Feb 25;263(6):2953-61 PMID: 2963821
  12. Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex.
    Cell. 1988 Jan 15;52(1):85-95 PMID: 3278811
  13. Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies.
    EMBO J. 1989 Dec 1;8(12):3651-6 PMID: 2583115
  14. Assembly, intracellular processing, and expression at the cell surface of the human alpha beta T cell receptor/CD3 complex. Function of the CD3-zeta chain.
    J Immunol. 1989 Dec 15;143(12):4069-77 PMID: 2531776
  15. Lysine 271 in the transmembrane domain of the T-cell antigen receptor beta chain is necessary for its assembly with the CD3 complex but not for alpha/beta dimerization.
    J Biol Chem. 1990 Mar 5;265(7):4131-5 PMID: 2137462
  16. Assembly and function of the T cell antigen receptor. Requirement of either the lysine or arginine residues in the transmembrane region of the alpha chain.
    J Biol Chem. 1990 Aug 15;265(23):14036-43 PMID: 2143190
  17. Structure of the T-cell antigen receptor: evidence for two CD3 epsilon subunits in the T-cell receptor-CD3 complex.
    Proc Natl Acad Sci U S A. 1990 Sep;87(18):7220-4 PMID: 2144901
  18. Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains.
    Cell. 1990 Nov 2;63(3):503-13 PMID: 2225064
  19. Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex.
    J Exp Med. 1991 Jan 1;173(1):7-17 PMID: 1824636
  20. The T cell antigen receptor: insights into organelle biology.
    Annu Rev Cell Biol. 1990;6:403-31 PMID: 2275818
  21. Membrane protein association by potential intramembrane charge pairs.
    Nature. 1991 May 30;351(6325):414-6 PMID: 1827877
  22. Role of potentially charged transmembrane residues in targeting proteins for retention and degradation within the endoplasmic reticulum.
    EMBO J. 1991 Oct;10(10):2783-93 PMID: 1915263
  23. Structure, assembly and intracellular transport of the T cell receptor for antigen.
    Semin Immunol. 1991 Sep;3(5):283-97 PMID: 1686832
  24. Failure to synthesize the CD3-gamma chain. Consequences for T cell antigen receptor assembly, processing, and expression.
    J Immunol. 1992 Apr 15;148(8):2437-45 PMID: 1532815
  25. Independent and synergistic effects of disulfide bond formation, beta 2-microglobulin, and peptides on class I MHC folding and assembly in an in vitro translation system.
    J Immunol. 1992 Nov 1;149(9):2935-44 PMID: 1401922
  26. Associations between subunit ectodomains promote T cell antigen receptor assembly and protect against degradation in the ER.
    J Cell Biol. 1993 Jul;122(1):67-78 PMID: 8314847
  27. Assembly of HLA DR1 molecules translated in vitro: binding of peptide in the endoplasmic reticulum precludes association with invariant chain.
    EMBO J. 1994 Jun 1;13(11):2699-707 PMID: 8013468
  28. Stoichiometry of the T cell antigen receptor (TCR) complex: each TCR/CD3 complex contains one TCR alpha, one TCR beta, and two CD3 epsilon chains.
    J Exp Med. 1994 Aug 1;180(2):587-93 PMID: 8046335
  29. TCR alpha-CD3 delta epsilon association is the initial step in alpha beta dimer formation in murine T cells and is limiting in immature CD4+ CD8+ thymocytes.
    Immunity. 1995 Apr;2(4):391-9 PMID: 7719941
  30. Evidence for multivalent structure of T-cell antigen receptor complex.
    Mol Immunol. 1995 Aug;32(11):829-39 PMID: 7675043
  31. Analysis of the T-cell receptor repertoire of human T-cell leukemia virus type 1 (HTLV-1) Tax-specific CD8+ cytotoxic T lymphocytes from patients with HTLV-1-associated disease: evidence for oligoclonal expansion.
    J Virol. 1996 Feb;70(2):843-51 PMID: 8551623
  32. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2.
    Nature. 1996 Nov 14;384(6605):134-41 PMID: 8906788
  33. T cell receptor biochemistry, repertoire selection and general features of TCR and Ig structure.
    Ciba Found Symp. 1997;204:94-100; discussion 100-4 PMID: 9107414
  34. In vitro translation and assembly of a complete T cell receptor-CD3 complex.
    J Exp Med. 1997 Aug 4;186(3):393-403 PMID: 9236191
  35. Pre-TCR/CD3 and TCR/CD3 complexes: decamers with differential signalling properties?
    Immunol Today. 1997 Dec;18(12):565-9 PMID: 9425732
  36. Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. Evidence for a double TCR heterodimer model.
    Eur J Immunol. 1998 Jan;28(1):12-21 PMID: 9485181
  37. Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation.
    Science. 1999 Feb 12;283(5404):987-90 PMID: 9974392
  38. Erythropoietin receptor activation by a ligand-induced conformation change.
    Science. 1999 Feb 12;283(5404):990-3 PMID: 9974393
  39. Multivalent structure of an alphabetaT cell receptor.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1547-52 PMID: 9990061
  40. Protein folding and maturation in a cell-free system.
    Biochem Cell Biol. 1998;76(5):867-73 PMID: 10353722
  41. TCRzeta is transported to and retained in the Golgi apparatus independently of other TCR chains: implications for TCR assembly.
    Eur J Immunol. 1999 May;29(5):1719-28 PMID: 10359127
  42. Pairwise, cooperative and inhibitory interactions describe the assembly and probable structure of the T-cell antigen receptor.
    EMBO J. 1991 Jul;10(7):1643-51 PMID: 1828760
  43. Structure of the complete extracellular domain of the common beta subunit of the human GM-CSF, IL-3, and IL-5 receptors reveals a novel dimer configuration.
    Cell. 2001 Jan 26;104(2):291-300 PMID: 11207369
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600245
Published
2004-06-16
Epub
2004-00-20
Pages
2348-57
Language
English
Region
England
NLM ID
8208664
PMCID
PMC423287
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600245 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2