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PMID: 1824636 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex.

The Journal of experimental medicine ·Vol. 173 ·No. 1 ·1991-01-01 ·Pages 7-17

de la Hera A, Müller U, Olsson C, Isaaz S, Tunnacliffe A

Abstract

Transgenic mice carrying and expressing the human CD3 epsilon gene incorporate the corresponding protein product into T cell receptor (TCR)/CD3 complexes on thymocyte and T cell surfaces. The chimeric antigen receptors allow normal T cell development and selection of repertoires in vivo and are able to transduce activation signals in vitro. We have exploited the ability to distinguish mouse (m) and human (h)CD3 epsilon chains to analyze the stoichiometry of CD3 epsilon in transgenic mouse TCRs. Immunoprecipitation and fluorescence resonance energy transfer experiments demonstrate that such TCRs can contain both h- and mCD3 epsilon chains, implying that more than one CD3 epsilon subunit occurs per TCR. Antigen comodulation studies are consistent with a stochastic use of h- or mCD3 epsilon during receptor assembly, and further suggest a structure for the TCR/CD3 complex with two CD3 epsilon chains. The determination of CD3 epsilon subunit stoichiometry, together with existing biochemical data, allows the generation of a minimal model for the structure of the TCR and illustrates the potential value of the transgenic approach to the analysis of complex receptors.

MeSH Terms
Animals Antigens, Differentiation, T-Lymphocyte/chemistry CD3 Complex Fluorescence Humans Mice Mice, Transgenic Precipitin Tests Receptors, Antigen, T-Cell/analysis,chemistry T-Lymphocytes/immunology
Chemicals
Antigens, Differentiation, T-Lymphocyte CD3 Complex Receptors, Antigen, T-Cell antigen T cell receptor, epsilon chain
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
de la Hera A
Basel Institute for Immunology, Switzerland.
Müller U
Olsson C
Isaaz S
Tunnacliffe A
References (45)
45 references, click to expand
  1. The T cell receptor/CD3 complex: a dynamic protein ensemble.
    Annu Rev Immunol. 1988;6:629-62 PMID: 3289580
  2. Identification of a monoclonal antibody specific for a murine T3 polypeptide.
    Proc Natl Acad Sci U S A. 1987 Mar;84(5):1374-8 PMID: 2950524
  3. Most anti-human CD3 monoclonal antibodies are directed to the CD3 epsilon subunit.
    Eur J Immunol. 1989 May;19(5):947-50 PMID: 2472280
  4. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors.
    J Immunol. 1989 Apr 15;142(8):2736-42 PMID: 2467936
  5. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors.
    Nature. 1988 Sep 29;335(6189):443-5 PMID: 2458531
  6. Flow cytometric resonance energy transfer measurements support the association of a 95-kDa peptide termed T27 with the 55-kDa Tac peptide.
    Proc Natl Acad Sci U S A. 1987 Oct;84(20):7246-50 PMID: 2444977
  7. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor.
    J Immunol. 1985 Jun;134(6):3994-4000 PMID: 2580901
  8. Kinases and phosphatases in T-cell activation.
    Immunol Today. 1989 Jun;10(6):200-5 PMID: 2546570
  9. The MHC molecule I-E is necessary but not sufficient for the clonal deletion of V beta 11-bearing T cells.
    J Exp Med. 1989 Apr 1;169(4):1405-19 PMID: 2538552
  10. T-cell antigen receptor (TCR)-alpha/beta heterodimer formation is a prerequisite for association of CD3-zeta 2 into functionally competent TCR.CD3 complexes.
    J Biol Chem. 1989 Dec 5;264(34):20760-9 PMID: 2531145
  11. T-cell receptor-CD4 physical association in a murine T-cell hybridoma: induction by antigen receptor ligation.
    Proc Natl Acad Sci U S A. 1989 Nov;86(21):8531-5 PMID: 2530583
  12. Activation-driven programmed cell death and T cell receptor zeta eta expression.
    Science. 1989 Dec 1;246(4934):1162-5 PMID: 2531464
  13. 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
  14. T-cell receptor delta-chain can substitute for alpha to form a beta delta heterodimer.
    Nature. 1989 Aug 17;340(6234):562-5 PMID: 2528071
  15. Alpha beta T cell receptor and CD3 transduce different signals in immature T cells. Implications for selection and tolerance.
    J Immunol. 1989 May 1;142(9):3006-12 PMID: 2523422
  16. The mouse CD3-gamma, -delta, and -epsilon genes reside within 50 kilobases on chromosome 9, whereas CD3-zeta maps to chromosome 1, band H.
    Immunogenetics. 1989;29(4):265-8 PMID: 2522910
  17. The T cell receptor V beta 6 domain imparts reactivity to the Mls-1a antigen.
    Cell Immunol. 1989 Apr 1;119(2):412-26 PMID: 2522825
  18. Triggering T cells by otherwise inert hybrid anti-CD3/antitumor antibodies requires encounter with the specific target cell.
    J Exp Med. 1989 Jul 1;170(1):297-302 PMID: 2526194
  19. The thymus selects the useful, neglects the useless and destroys the harmful.
    Immunol Today. 1989 Feb;10(2):57-61 PMID: 2526642
  20. 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
  21. 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
  22. Subunit interactions within the T-cell antigen receptor: clues from the study of partial complexes.
    Proc Natl Acad Sci U S A. 1988 Sep;85(18):6929-33 PMID: 3261872
  23. Use of fluorescent antibodies in the study of lymphoid cell membrane molecules.
    Methods Enzymol. 1984;108:413-25 PMID: 6084798
  24. Building a multichain receptor: synthesis, degradation, and assembly of the T-cell antigen receptor.
    Proc Natl Acad Sci U S A. 1987 May;84(9):2688-92 PMID: 3495001
  25. Activators of protein kinase C down-regulate and phosphorylate the T3/T-cell antigen receptor complex of human T lymphocytes.
    Proc Natl Acad Sci U S A. 1985 Dec;82(23):8158-62 PMID: 3934668
  26. 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
  27. Characterization of the CD3 gamma and delta invariant subunits of the sheep T cell antigen receptor.
    Eur J Immunol. 1990 Jul;20(7):1505-11 PMID: 2143727
  28. Molecular cloning of the CD3 eta subunit identifies a CD3 zeta-related product in thymus-derived cells.
    Proc Natl Acad Sci U S A. 1990 May;87(9):3319-23 PMID: 2139725
  29. The implications of subunit interactions for the structure of the T cell receptor-CD3 complex.
    Eur J Immunol. 1990 Feb;20(2):299-305 PMID: 2138083
  30. Clonotypic structures involved in antigen-specific human T cell function. Relationship to the T3 molecular complex.
    J Exp Med. 1983 Feb 1;157(2):705-19 PMID: 6185617
  31. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor.
    Nature. 1983 Jun 30;303(5920):808-10 PMID: 6191218
  32. Distinctive functional characteristics of human "T" lymphocytes defined by E rosetting or a monoclonal anti-T cell antibody.
    Eur J Immunol. 1981 Apr;11(4):329-34 PMID: 6788570
  33. OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties.
    J Immunol. 1980 Jun;124(6):2708-13 PMID: 6966296
  34. The majority of human CD3 epitopes are conferred by the epsilon chain.
    Int Immunol. 1989;1(5):546-50 PMID: 2484963
  35. Delineation of human thymocytes with or without functional potential by CD1-specific antibodies.
    Int Immunol. 1989;1(5):496-502 PMID: 2484962
  36. Disulfide linkage of the zeta and eta chains of the T cell receptor. Possible identification of two structural classes of receptors.
    J Biol Chem. 1988 Jul 15;263(20):9874-8 PMID: 3290215
  37. Flow cytometric measurements of fluorescence energy transfer using single laser excitation.
    Cytometry. 1987 Mar;8(2):120-8 PMID: 3582060
  38. Molecular organization of the human CD3 gene family on chromosome 11q23.
    Immunogenetics. 1988;28(5):365-73 PMID: 2971614
  39. T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis.
    Science. 1988 Oct 28;242(4878):571-4 PMID: 2845582
  40. Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex.
    Proc Natl Acad Sci U S A. 1988 Dec;85(24):9709-13 PMID: 2974162
  41. Organization of the human CD3 locus on chromosome 11.
    Eur J Immunol. 1988 Oct;18(10):1639-42 PMID: 2973415
  42. 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
  43. Transfection of genes encoding the T cell receptor-associated CD3 complex into COS cells results in assembly of the macromolecular structure.
    J Biol Chem. 1988 Jun 15;263(17):8528-36 PMID: 2967296
  44. Purification and identification by amino acid sequence analysis of the subunits of the CD3 antigen of human tonsil T-lymphocytes.
    Mol Immunol. 1987 Oct;24(10):1069-79 PMID: 2960887
  45. The immunoglobulin superfamily--domains for cell surface recognition.
    Annu Rev Immunol. 1988;6:381-405 PMID: 3289571
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.173.1.7
Published
1991-01-01
Pages
7-17
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2118768
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.173.1.7 PMC Full Text View journal details
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