Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1991 Aug 1;174(2):319–326. doi: 10.1084/jem.174.2.319

Expression and function of a variant T cell receptor complex lacking CD3-gamma

PMCID: PMC2118903  PMID: 1713248

Abstract

A T cell line termed DIL2 has been derived from an infant with a polyclonal T cell receptor (TCR)/CD3 cell surface expression defect. Indirect immunofluorescence showed that the expression of certain TCR/CD3 epitopes (like those detected by WT31 and BMA031 monoclonals) was strongly reduced (around five-fold) on DIL2, whereas other epitopes (like those detected by SP34 and Leu4) were only around two-fold lower than in normal T cell lines. Specific immunoprecipitates of surface- radioiodinated DIL2 cells contained TCR-alpha, TCR-beta, CD3-delta, CD3- epsilon and TCR-zeta chains, but lacked CD3-gamma. This structural TCR/CD3 variant was, however, capable of transducing certain activation signals, since normal proliferation and a low but significant calcium flux was observed in DIL2 cells after engagement with specific antibodies. Our data suggest that a functional TCR/CD3 complex can be expressed on the surface of T cells in the absence of CD3-gamma.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Alarcon B., Berkhout B., Breitmeyer J., Terhorst C. 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):2953–2961. [PubMed] [Google Scholar]
  2. Alarcon B., Regueiro J. R., Arnaiz-Villena A., Terhorst C. Familial defect in the surface expression of the T-cell receptor-CD3 complex. N Engl J Med. 1988 Nov 3;319(18):1203–1208. doi: 10.1056/NEJM198811033191806. [DOI] [PubMed] [Google Scholar]
  3. Alarcon B., Terhorst C., Arnaiz-Villena A., Perez-Aciego P., Regueiro J. R. Congenital T-cell receptor immunodeficiencies in man. Immunodefic Rev. 1990;2(1):1–16. [PubMed] [Google Scholar]
  4. Arnaiz-Villena A., Perez-Aciego P., Ballestin C., Sotelo T., Perez-Seoane C., Martin-Villa J. M., Regueiro J. R. Biochemical basis of a novel T lymphocyte receptor immunodeficiency by immunohistochemistry. A possible CD3 gamma abnormality. Lab Invest. 1991 May;64(5):675–681. [PubMed] [Google Scholar]
  5. Berkhout B., Alarcon B., Terhorst C. 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):8528–8536. [PubMed] [Google Scholar]
  6. Blumberg R. S., Ley S., Sancho J., Lonberg N., Lacy E., McDermott F., Schad V., Greenstein J. L., Terhorst C. 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):7220–7224. doi: 10.1073/pnas.87.18.7220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bonifacino J. S., Chen C., Lippincott-Schwartz J., Ashwell J. D., Klausner R. D. 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):6929–6933. doi: 10.1073/pnas.85.18.6929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brenner M. B., Trowbridge I. S., Strominger J. L. 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):183–190. doi: 10.1016/0092-8674(85)90321-6. [DOI] [PubMed] [Google Scholar]
  9. Carrel S., Moretta A., Pantaleo G., Tambussi G., Isler P., Perussia B., Cerottini J. C. Stimulation and proliferation of CD4+ peripheral blood T lymphocytes induced by an anti-CD4 monoclonal antibody. Eur J Immunol. 1988 Mar;18(3):333–339. doi: 10.1002/eji.1830180303. [DOI] [PubMed] [Google Scholar]
  10. Charmley P., Sanal O., Wei S., Chou A., Terhorst C., Gatti R. A. Human T-cell receptor CD3-epsilon (CD3E)/TaqI DNA polymorphism. Nucleic Acids Res. 1989 Mar 25;17(6):2374–2374. doi: 10.1093/nar/17.6.2374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Clevers H., Alarcon B., Wileman T., Terhorst C. The T cell receptor/CD3 complex: a dynamic protein ensemble. Annu Rev Immunol. 1988;6:629–662. doi: 10.1146/annurev.iy.06.040188.003213. [DOI] [PubMed] [Google Scholar]
  12. Geisler C., Schøller J., Wahi M. A., Rubin B., Weiss A. Association of the human CD3-zeta chain with the alpha beta-T cell receptor/CD3 complex. Clues from a T cell variant with a mutated T cell receptor-alpha chain. J Immunol. 1990 Sep 15;145(6):1761–1767. [PubMed] [Google Scholar]
  13. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  14. Imboden J. B., Stobo J. D. Transmembrane signalling by the T cell antigen receptor. Perturbation of the T3-antigen receptor complex generates inositol phosphates and releases calcium ions from intracellular stores. J Exp Med. 1985 Mar 1;161(3):446–456. doi: 10.1084/jem.161.3.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Lerch P. G., van de Rijn M., Smart J. E., Knowles R. W., Terhorst C. Isolation and purification of the human thymocyte antigens T6 and M241. Mol Immunol. 1986 Feb;23(2):131–139. doi: 10.1016/0161-5890(86)90034-9. [DOI] [PubMed] [Google Scholar]
  18. Ley S. C., Tan K. N., Kubo R., Sy M. S., Terhorst C. Surface expression of CD3 in the absence of T cell receptor (TcR): evidence for sorting of partial TcR/CD3 complexes in a post-endoplasmic reticulum compartment. Eur J Immunol. 1989 Dec;19(12):2309–2317. doi: 10.1002/eji.1830191220. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Regueiro J. R., Arnaiz-Villena A., Ortiz de Landázuri M., Martín Villa J. M., Vicario J. L., Pascual-Ruiz V., Guerra-Garcia F., Alcamí J., López-Botet M., Manzanares J. Familial defect of CD3 (T3) expression by T cells associated with rare gut epithelial cell autoantibodies. Lancet. 1986 May 31;1(8492):1274–1275. doi: 10.1016/s0140-6736(86)91413-3. [DOI] [PubMed] [Google Scholar]
  21. Regueiro J. R., López-Botet M., De Landazuri M. O., Alcami J., Corell A., Martín-Villa J. M., Vicario J. L., Arnaiz-Villena A. An in vivo functional immune system lacking polyclonal T-cell surface expression of the CD3/Ti(WT31) complex. Scand J Immunol. 1987 Dec;26(6):699–708. doi: 10.1111/j.1365-3083.1987.tb02306.x. [DOI] [PubMed] [Google Scholar]
  22. Sancho J., Chatila T., Wong R. C., Hall C., Blumberg R., Alarcon B., Geha R. S., Terhorst C. 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):20760–20769. [PubMed] [Google Scholar]
  23. Thoenes G., Le Deist F., Fischer A., Griscelli C., Lisowska-Grospierre B. Immunodeficiency associated with defective expression of the T-cell receptor-CD3 complex. N Engl J Med. 1990 May 10;322(19):1399–1399. doi: 10.1056/NEJM199005103221919. [DOI] [PubMed] [Google Scholar]
  24. Transy C., Moingeon P., Stebbins C., Reinherz E. L. Deletion of the cytoplasmic region of the CD3 epsilon subunit does not prevent assembly of a functional T-cell receptor. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7108–7112. doi: 10.1073/pnas.86.18.7108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wileman T., Carson G. R., Concino M., Ahmed A., Terhorst C. The gamma and epsilon subunits of the CD3 complex inhibit pre-Golgi degradation of newly synthesized T cell antigen receptors. J Cell Biol. 1990 Apr;110(4):973–986. doi: 10.1083/jcb.110.4.973. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES