Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Nov 1;182(5):1585–1590. doi: 10.1084/jem.182.5.1585

The pre-T cell receptor (TCR) complex is functionally coupled to the TCR-zeta subunit

PMCID: PMC2192214  PMID: 7595229

Abstract

The pre-T cell receptor (TCR) complex regulates early T cell development and consists of a heterodimer of the TCR-beta subunit in association with the pre-TCR-alpha chain. Notably, in contrast to alpha/beta-expressing T cells, several studies suggested that the TCR- zeta chain is not stably associated with this pre-TCR complex. To examine the proximal signaling processes mediated by the pre-TCR complex and the role of the TCR-zeta chain in these processes, we stimulated pre-TCR-expressing cells and analyzed the interactions of the TCR/CD3 invariant chains with the Syk/ZAP-70 family of protein tyrosine kinases. Stimulation of the pre-TCR complex led to the tyrosine phosphorylation of the CD3 epsilon and TCR-zeta chains, as well as the phosphorylation and association of ZAP-70 and Syk with phosphorylated CD3 epsilon and TCR-zeta. These results demonstrate that the pre-TCR complex is functionally coupled to the TCR-zeta subunit and to the ZAP-70 and Syk protein tyrosine kinases.

Full Text

The Full Text of this article is available as a PDF (852.2 KB).

Selected References

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

  1. Chan A. C., Irving B. A., Fraser J. D., Weiss A. The zeta chain is associated with a tyrosine kinase and upon T-cell antigen receptor stimulation associates with ZAP-70, a 70-kDa tyrosine phosphoprotein. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9166–9170. doi: 10.1073/pnas.88.20.9166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chan A. C., Iwashima M., Turck C. W., Weiss A. ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR zeta chain. Cell. 1992 Nov 13;71(4):649–662. doi: 10.1016/0092-8674(92)90598-7. [DOI] [PubMed] [Google Scholar]
  3. Duplay P., Thome M., Hervé F., Acuto O. p56lck interacts via its src homology 2 domain with the ZAP-70 kinase. J Exp Med. 1994 Apr 1;179(4):1163–1172. doi: 10.1084/jem.179.4.1163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Groettrup M., Ungewiss K., Azogui O., Palacios R., Owen M. J., Hayday A. C., von Boehmer H. A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor beta chain and a 33 kd glycoprotein. Cell. 1993 Oct 22;75(2):283–294. doi: 10.1016/0092-8674(93)80070-u. [DOI] [PubMed] [Google Scholar]
  5. Groettrup M., von Boehmer H. A role for a pre-T-cell receptor in T-cell development. Immunol Today. 1993 Dec;14(12):610–614. doi: 10.1016/0167-5699(93)90201-U. [DOI] [PubMed] [Google Scholar]
  6. Groettrup M., von Boehmer H. T cell receptor beta chain dimers on immature thymocytes from normal mice. Eur J Immunol. 1993 Jun;23(6):1393–1396. doi: 10.1002/eji.1830230633. [DOI] [PubMed] [Google Scholar]
  7. Irving B. A., Chan A. C., Weiss A. Functional characterization of a signal transducing motif present in the T cell antigen receptor zeta chain. J Exp Med. 1993 Apr 1;177(4):1093–1103. doi: 10.1084/jem.177.4.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Irving B. A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-o. [DOI] [PubMed] [Google Scholar]
  9. Kishi H., Borgulya P., Scott B., Karjalainen K., Traunecker A., Kaufman J., von Boehmer H. Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells. EMBO J. 1991 Jan;10(1):93–100. doi: 10.1002/j.1460-2075.1991.tb07924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuwabara I., Ohno H., Punt J. A., Hashimoto Y., Saito T. Transition from TCR-beta dimer to TCR-alpha beta-expressing cells by introduction of an alpha-chain in an immature thymocyte cell line. J Immunol. 1994 Mar 1;152(5):2148–2156. [PubMed] [Google Scholar]
  11. Letourneur F., Klausner R. D. Activation of T cells by a tyrosine kinase activation domain in the cytoplasmic tail of CD3 epsilon. Science. 1992 Jan 3;255(5040):79–82. doi: 10.1126/science.1532456. [DOI] [PubMed] [Google Scholar]
  12. Liu C. P., Ueda R., She J., Sancho J., Wang B., Weddell G., Loring J., Kurahara C., Dudley E. C., Hayday A. Abnormal T cell development in CD3-zeta-/- mutant mice and identification of a novel T cell population in the intestine. EMBO J. 1993 Dec;12(12):4863–4875. doi: 10.1002/j.1460-2075.1993.tb06176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Love P. E., Shores E. W., Johnson M. D., Tremblay M. L., Lee E. J., Grinberg A., Huang S. P., Singer A., Westphal H. T cell development in mice that lack the zeta chain of the T cell antigen receptor complex. Science. 1993 Aug 13;261(5123):918–921. doi: 10.1126/science.7688481. [DOI] [PubMed] [Google Scholar]
  14. Madrenas J., Wange R. L., Wang J. L., Isakov N., Samelson L. E., Germain R. N. Zeta phosphorylation without ZAP-70 activation induced by TCR antagonists or partial agonists. Science. 1995 Jan 27;267(5197):515–518. doi: 10.1126/science.7824949. [DOI] [PubMed] [Google Scholar]
  15. Malissen M., Gillet A., Rocha B., Trucy J., Vivier E., Boyer C., Köntgen F., Brun N., Mazza G., Spanopoulou E. T cell development in mice lacking the CD3-zeta/eta gene. EMBO J. 1993 Nov;12(11):4347–4355. doi: 10.1002/j.1460-2075.1993.tb06119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mombaerts P., Clarke A. R., Rudnicki M. A., Iacomini J., Itohara S., Lafaille J. J., Wang L., Ichikawa Y., Jaenisch R., Hooper M. L. Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages. Nature. 1992 Nov 19;360(6401):225–231. doi: 10.1038/360225a0. [DOI] [PubMed] [Google Scholar]
  17. Nakayama T., Singer A., Hsi E. D., Samelson L. E. Intrathymic signalling in immature CD4+CD8+ thymocytes results in tyrosine phosphorylation of the T-cell receptor zeta chain. Nature. 1989 Oct 19;341(6243):651–654. doi: 10.1038/341651a0. [DOI] [PubMed] [Google Scholar]
  18. Saint-Ruf C., Ungewiss K., Groettrup M., Bruno L., Fehling H. J., von Boehmer H. Analysis and expression of a cloned pre-T cell receptor gene. Science. 1994 Nov 18;266(5188):1208–1212. doi: 10.1126/science.7973703. [DOI] [PubMed] [Google Scholar]
  19. Shinkai Y., Rathbun G., Lam K. P., Oltz E. M., Stewart V., Mendelsohn M., Charron J., Datta M., Young F., Stall A. M. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992 Mar 6;68(5):855–867. doi: 10.1016/0092-8674(92)90029-c. [DOI] [PubMed] [Google Scholar]
  20. Shores E. W., Huang K., Tran T., Lee E., Grinberg A., Love P. E. Role of TCR zeta chain in T cell development and selection. Science. 1994 Nov 11;266(5187):1047–1050. doi: 10.1126/science.7526464. [DOI] [PubMed] [Google Scholar]
  21. Sloan-Lancaster J., Shaw A. S., Rothbard J. B., Allen P. M. Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy. Cell. 1994 Dec 2;79(5):913–922. doi: 10.1016/0092-8674(94)90080-9. [DOI] [PubMed] [Google Scholar]
  22. Wegener A. M., Letourneur F., Hoeveler A., Brocker T., Luton F., Malissen B. The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules. Cell. 1992 Jan 10;68(1):83–95. doi: 10.1016/0092-8674(92)90208-t. [DOI] [PubMed] [Google Scholar]
  23. Weiss A., Littman D. R. Signal transduction by lymphocyte antigen receptors. Cell. 1994 Jan 28;76(2):263–274. doi: 10.1016/0092-8674(94)90334-4. [DOI] [PubMed] [Google Scholar]
  24. Weiss A. T cell antigen receptor signal transduction: a tale of tails and cytoplasmic protein-tyrosine kinases. Cell. 1993 Apr 23;73(2):209–212. doi: 10.1016/0092-8674(93)90221-b. [DOI] [PubMed] [Google Scholar]
  25. van Oers N. S., Killeen N., Weiss A. ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR zeta in murine thymocytes and lymph node T cells. Immunity. 1994 Nov;1(8):675–685. doi: 10.1016/1074-7613(94)90038-8. [DOI] [PubMed] [Google Scholar]
  26. van Oers N. S., Teh S. J., Irving B. A., Tiong J., Weiss A., Teh H. S. Production and characterization of monoclonal antibodies specific for the murine T cell receptor zeta chain. J Immunol Methods. 1994 Apr 15;170(2):261–268. doi: 10.1016/0022-1759(94)90401-4. [DOI] [PubMed] [Google Scholar]
  27. von Boehmer H. Developmental biology of T cells in T cell-receptor transgenic mice. Annu Rev Immunol. 1990;8:531–556. doi: 10.1146/annurev.iy.08.040190.002531. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES