Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1989 Dec 1;8(12):3651–3656. doi: 10.1002/j.1460-2075.1989.tb08539.x

Role of the zeta chain in the expression of the T cell antigen receptor: genetic reconstitution studies.

A M Weissman 1, S J Frank 1, D G Orloff 1, M Merćep 1, J D Ashwell 1, R D Klausner 1
PMCID: PMC402047  PMID: 2583115

Abstract

The zeta (zeta) chain plays a central role in T cell antigen receptor assembly and signal transduction. From previous work in murine T cell hybridomas we have inferred that the zeta subunit is limiting in receptor assembly. Partial receptors made in excess of zeta are assembled in the endoplasmic reticulum, transported through the Golgi, but then rapidly and efficiently degraded in lysosomes. zeta would therefore seem to play a unique role in targeting receptors from the Golgi to the cell surface. To determine directly whether zeta limits receptor assembly we have reconstituted a zeta-deficient T cell line by transfection of the murine zeta cDNA. Transfection results in restoration of expression of surface T cell receptor. In addition, increasing zeta expression results in a commensurate increase in the survival of previously excess subunits. This is reflected in an increased surface expression of complete receptors. Finally, transfection of the zeta cDNA fails to produce detectable zeta-eta heterodimers. The implications of these findings with regard to receptor assembly, and the relationship between zeta and eta, are discussed.

Full text

PDF
3651

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison J. P., Lanier L. L. Structure, function, and serology of the T-cell antigen receptor complex. Annu Rev Immunol. 1987;5:503–540. doi: 10.1146/annurev.iy.05.040187.002443. [DOI] [PubMed] [Google Scholar]
  2. Baniyash M., Garcia-Morales P., Bonifacino J. S., Samelson L. E., Klausner R. D. 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):9874–9878. [PubMed] [Google Scholar]
  3. Baniyash M., Hsu V. W., Seldin M. F., Klausner R. D. The isolation and characterization of the murine T cell antigen receptor zeta chain gene. J Biol Chem. 1989 Aug 5;264(22):13252–13257. [PubMed] [Google Scholar]
  4. Borst J., Prendiville M. A., Terhorst C. The T3 complex on human thymus-derived lymphocytes contains two different subunits of 20 kDa. Eur J Immunol. 1983 Jul;13(7):576–580. doi: 10.1002/eji.1830130712. [DOI] [PubMed] [Google Scholar]
  5. Gold D. P., van Dongen J. J., Morton C. C., Bruns G. A., van den Elsen P., Geurts van Kessel A. H., Terhorst C. The gene encoding the epsilon subunit of the T3/T-cell receptor complex maps to chromosome 11 in humans and to chromosome 9 in mice. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1664–1668. doi: 10.1073/pnas.84.6.1664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gorman C. M., Howard B. H., Reeves R. Expression of recombinant plasmids in mammalian cells is enhanced by sodium butyrate. Nucleic Acids Res. 1983 Nov 11;11(21):7631–7648. doi: 10.1093/nar/11.21.7631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kanellopoulos J. M., Wigglesworth N. M., Owen M. J., Crumpton M. J. Biosynthesis and molecular nature of the T3 antigen of human T lymphocytes. EMBO J. 1983;2(10):1807–1814. doi: 10.1002/j.1460-2075.1983.tb01662.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. King S. M., Otter T., Witman G. B. Characterization of monoclonal antibodies against Chlamydomonas flagellar dyneins by high-resolution protein blotting. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4717–4721. doi: 10.1073/pnas.82.14.4717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krissansen G. W., Owen M. J., Verbi W., Crumpton M. J. Primary structure of the T3 gamma subunit of the T3/T cell antigen receptor complex deduced from cDNA sequences: evolution of the T3 gamma and delta subunits. EMBO J. 1986 Aug;5(8):1799–1808. doi: 10.1002/j.1460-2075.1986.tb04429.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Merćep M., Bonifacino J. S., Garcia-Morales P., Samelson L. E., Klausner R. D., Ashwell J. D. T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis. Science. 1988 Oct 28;242(4878):571–574. doi: 10.1126/science.2845582. [DOI] [PubMed] [Google Scholar]
  11. Minami Y., Weissman A. M., Samelson L. E., Klausner R. D. 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):2688–2692. doi: 10.1073/pnas.84.9.2688. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Oi V. T., Morrison S. L., Herzenberg L. A., Berg P. Immunoglobulin gene expression in transformed lymphoid cells. Proc Natl Acad Sci U S A. 1983 Feb;80(3):825–829. doi: 10.1073/pnas.80.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Orloff D. G., Frank S. J., Robey F. A., Weissman A. M., Klausner R. D. Biochemical characterization of the eta chain of the T-cell receptor. A unique subunit related to zeta. J Biol Chem. 1989 Sep 5;264(25):14812–14817. [PubMed] [Google Scholar]
  14. Saito T., Weiss A., Gunter K. C., Shevach E. M., Germain R. N. Cell surface T3 expression requires the presence of both alpha- and beta-chains of the T cell receptor. J Immunol. 1987 Jul 15;139(2):625–628. [PubMed] [Google Scholar]
  15. Saito T., Weiss A., Miller J., Norcross M. A., Germain R. N. Specific antigen-Ia activation of transfected human T cells expressing murine Ti alpha beta-human T3 receptor complexes. Nature. 1987 Jan 8;325(7000):125–130. doi: 10.1038/325125a0. [DOI] [PubMed] [Google Scholar]
  16. Samelson L. E., Harford J. B., Klausner R. D. Identification of the components of the murine T cell antigen receptor complex. Cell. 1985 Nov;43(1):223–231. doi: 10.1016/0092-8674(85)90027-3. [DOI] [PubMed] [Google Scholar]
  17. Samelson L. E., Schwartz R. H. T cell clone-specific alloantisera that inhibit or stimulate antigen-induced T cell activation. J Immunol. 1983 Dec;131(6):2645–2650. [PubMed] [Google Scholar]
  18. Sarkar G., Sommer S. S. RNA amplification with transcript sequencing (RAWTS). Nucleic Acids Res. 1988 Jun 10;16(11):5197–5197. doi: 10.1093/nar/16.11.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
  20. Sussman J. J., Bonifacino J. S., Lippincott-Schwartz J., Weissman A. M., Saito T., Klausner R. D., Ashwell J. D. 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. doi: 10.1016/0092-8674(88)90533-8. [DOI] [PubMed] [Google Scholar]
  21. Tunnacliffe A., Buluwela L., Rabbitts T. H. Physical linkage of three CD3 genes on human chromosome 11. EMBO J. 1987 Oct;6(10):2953–2957. doi: 10.1002/j.1460-2075.1987.tb02600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weissman A. M., Baniyash M., Hou D., Samelson L. E., Burgess W. H., Klausner R. D. Molecular cloning of the zeta chain of the T cell antigen receptor. Science. 1988 Feb 26;239(4843):1018–1021. doi: 10.1126/science.3278377. [DOI] [PubMed] [Google Scholar]
  23. Weissman A. M., Hou D., Orloff D. G., Modi W. S., Seuanez H., O'Brien S. J., Klausner R. D. 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):9709–9713. doi: 10.1073/pnas.85.24.9709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weissman A. M., Samelson L. E., Klausner R. D. A new subunit of the human T-cell antigen receptor complex. Nature. 1986 Dec 4;324(6096):480–482. doi: 10.1038/324480a0. [DOI] [PubMed] [Google Scholar]
  25. van den Elsen P., Bruns G., Gerhard D. S., Pravtcheva D., Jones C., Housman D., Ruddle F. A., Orkin S., Terhorst C. Assignment of the gene coding for the T3-delta subunit of the T3-T-cell receptor complex to the long arm of human chromosome 11 and to mouse chromosome 9. Proc Natl Acad Sci U S A. 1985 May;82(9):2920–2924. doi: 10.1073/pnas.82.9.2920. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES