Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jul;87(13):5021–5025. doi: 10.1073/pnas.87.13.5021

CD4-T-cell antigen receptor complexes on human leukemia T cells.

R S Chuck 1, C R Cantor 1, D B Tse 1
PMCID: PMC54253  PMID: 2195543

Abstract

CD4 and T-cell antigen receptor (TCR) comodulate from the surface of human and murine T cells following exposure to monoclonal anti-CD4 or anti-TCR. This comodulation may occur because expression of CD4 and TCR is regulated by similar transmembrane signals or because CD4 and TCR are physically associated. To study multimolecular assemblies on the plasma membrane, we developed a flow cytometric method for detecting singlet-singlet energy transfer between fluorescein isothiocyanate (FITC)- and tetramethylrhodamine isothiocyanate (TRITC)-conjugated monoclonal antibodies as sensitized TRITC emission on intact, single cells. Using this procedure, we detected CD4-TCR complexes on the surface of the transformed human leukemia T cells, HPB-ALL, in the absence of stimulation. More than one CD4 were found in association with one TCR. CD4-TCR complexes were not in rapid equilibrium with free CD4 and free TCR, and they were not induced by the dye-labeled anti-CD4 or anti-TCR.

Full text

PDF
5021

Selected References

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

  1. Anderson P., Blue M. L., Morimoto C., Schlossman S. F. Cross-linking of T3 (CD3) with T4 (CD4) enhances the proliferation of resting T lymphocytes. J Immunol. 1987 Aug 1;139(3):678–682. [PubMed] [Google Scholar]
  2. Anderson P., Blue M. L., Schlossman S. F. Comodulation of CD3 and CD4. Evidence for a specific association between CD4 and approximately 5% of the CD3:T cell receptor complexes on helper T lymphocytes. J Immunol. 1988 Mar 15;140(6):1732–1737. [PubMed] [Google Scholar]
  3. Bank I., Chess L. Perturbation of the T4 molecule transmits a negative signal to T cells. J Exp Med. 1985 Oct 1;162(4):1294–1303. doi: 10.1084/jem.162.4.1294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bray D., White J. G. Cortical flow in animal cells. Science. 1988 Feb 19;239(4842):883–888. doi: 10.1126/science.3277283. [DOI] [PubMed] [Google Scholar]
  5. Cantor C. R., Pechukas P. Determination of distance distribution functions by singlet-singlet energy transfer. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2099–2101. doi: 10.1073/pnas.68.9.2099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Damjanovich S., Trón L., Szöllösi J., Zidovetzki R., Vaz W. L., Regateiro F., Arndt-Jovin D. J., Jovin T. M. Distribution and mobility of murine histocompatibility H-2Kk antigen in the cytoplasmic membrane. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5985–5989. doi: 10.1073/pnas.80.19.5985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davies A. A., Cantrell D. A., Hexham J. M., Parker P. J., Rothbard J., Crumpton M. J. The human T3 gamma chain is phosphorylated at serine 126 in response to T lymphocyte activation. J Biol Chem. 1987 Aug 15;262(23):10918–10921. [PubMed] [Google Scholar]
  8. Diamond D. C., Sleckman B. P., Gregory T., Lasky L. A., Greenstein J. L., Burakoff S. J. Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. J Immunol. 1988 Dec 1;141(11):3715–3717. [PubMed] [Google Scholar]
  9. Fairclough R. H., Cantor C. R. The use of singlet-singlet energy transfer to study macromolecular assemblies. Methods Enzymol. 1978;48:347–379. doi: 10.1016/s0076-6879(78)48019-x. [DOI] [PubMed] [Google Scholar]
  10. Gallagher P. F., Fazekas de St Groth B., Miller J. F. CD4 and CD8 molecules can physically associate with the same T-cell receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10044–10048. doi: 10.1073/pnas.86.24.10044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gay D., Buus S., Pasternak J., Kappler J., Marrack P. The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5629–5633. doi: 10.1073/pnas.85.15.5629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hoxie J. A., Matthews D. M., Callahan K. J., Cassel D. L., Cooper R. A. Transient modulation and internalization of T4 antigen induced by phorbol esters. J Immunol. 1986 Aug 15;137(4):1194–1201. [PubMed] [Google Scholar]
  13. Hoxie J. A., Rackowski J. L., Haggarty B. S., Gaulton G. N. T4 endocytosis and phosphorylation induced by phorbol esters but not by mitogen or HIV infection. J Immunol. 1988 Feb 1;140(3):786–795. [PubMed] [Google Scholar]
  14. Janeway C. A., Jr The role of CD4 in T-cell activation: accessory molecule or co-receptor? Immunol Today. 1989 Jul;10(7):234–238. doi: 10.1016/0167-5699(89)90260-0. [DOI] [PubMed] [Google Scholar]
  15. Klausner R. D., O'Shea J. J., Luong H., Ross P., Bluestone J. A., Samelson L. E. T cell receptor tyrosine phosphorylation. Variable coupling for different activating ligands. J Biol Chem. 1987 Sep 15;262(26):12654–12659. [PubMed] [Google Scholar]
  16. Krangel M. S. Endocytosis and recycling of the T3-T cell receptor complex. The role of T3 phosphorylation. J Exp Med. 1987 Apr 1;165(4):1141–1159. doi: 10.1084/jem.165.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kupfer A., Singer S. J., Janeway C. A., Jr, Swain S. L. Coclustering of CD4 (L3T4) molecule with the T-cell receptor is induced by specific direct interaction of helper T cells and antigen-presenting cells. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5888–5892. doi: 10.1073/pnas.84.16.5888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ledbetter J. A., June C. H., Grosmaire L. S., Rabinovitch P. S. Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1384–1388. doi: 10.1073/pnas.84.5.1384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ledbetter J. A., June C. H., Rabinovitch P. S., Grossmann A., Tsu T. T., Imboden J. B. Signal transduction through CD4 receptors: stimulatory vs. inhibitory activity is regulated by CD4 proximity to the CD3/T cell receptor. Eur J Immunol. 1988 Apr;18(4):525–532. doi: 10.1002/eji.1830180406. [DOI] [PubMed] [Google Scholar]
  20. Littman D. R. The structure of the CD4 and CD8 genes. Annu Rev Immunol. 1987;5:561–584. doi: 10.1146/annurev.iy.05.040187.003021. [DOI] [PubMed] [Google Scholar]
  21. Meuer S. C., Acuto O., Hercend T., Schlossman S. F., Reinherz E. L. The human T-cell receptor. Annu Rev Immunol. 1984;2:23–50. doi: 10.1146/annurev.iy.02.040184.000323. [DOI] [PubMed] [Google Scholar]
  22. Mittler R. S., Goldman S. J., Spitalny G. L., Burakoff S. J. 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):8531–8535. doi: 10.1073/pnas.86.21.8531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. O'Neill H. C., McGrath M. S., Allison J. P., Weissman I. L. A subset of T cell receptors associated with L3T4 molecules mediates C6VL leukemia cell binding of its cognate retrovirus. Cell. 1987 Apr 10;49(1):143–151. doi: 10.1016/0092-8674(87)90764-1. [DOI] [PubMed] [Google Scholar]
  24. Oettgen H. C., Pettey C. L., Maloy W. L., Terhorst C. A T3-like protein complex associated with the antigen receptor on murine T cells. Nature. 1986 Mar 20;320(6059):272–275. doi: 10.1038/320272a0. [DOI] [PubMed] [Google Scholar]
  25. Rivas A., Takada S., Koide J., Sonderstrup-McDevitt G., Engleman E. G. CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells. J Immunol. 1988 May 1;140(9):2912–2918. [PubMed] [Google Scholar]
  26. Rojo J. M., Saizawa K., Janeway C. A., Jr Physical association of CD4 and the T-cell receptor can be induced by anti-T-cell receptor antibodies. Proc Natl Acad Sci U S A. 1989 May;86(9):3311–3315. doi: 10.1073/pnas.86.9.3311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rudd C. E., Trevillyan J. M., Dasgupta J. D., Wong L. L., Schlossman S. F. The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5190–5194. doi: 10.1073/pnas.85.14.5190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saizawa K., Rojo J., Janeway C. A., Jr Evidence for a physical association of CD4 and the CD3:alpha:beta T-cell receptor. Nature. 1987 Jul 16;328(6127):260–263. doi: 10.1038/328260a0. [DOI] [PubMed] [Google Scholar]
  29. Sheetz M. P., Turney S., Qian H., Elson E. L. Nanometre-level analysis demonstrates that lipid flow does not drive membrane glycoprotein movements. Nature. 1989 Jul 27;340(6231):284–288. doi: 10.1038/340284a0. [DOI] [PubMed] [Google Scholar]
  30. Sibley D. R., Benovic J. L., Caron M. G., Lefkowitz R. J. Regulation of transmembrane signaling by receptor phosphorylation. Cell. 1987 Mar 27;48(6):913–922. doi: 10.1016/0092-8674(87)90700-8. [DOI] [PubMed] [Google Scholar]
  31. Szöllösi J., Damjanovich S., Goldman C. K., Fulwyler M. J., Aszalos A. A., Goldstein G., Rao P., Talle M. A., Waldmann T. A. 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):7246–7250. doi: 10.1073/pnas.84.20.7246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tse D. B., Pernis B. Spontaneous internalization of Class I major histocompatibility complex molecules in T lymphoid cells. J Exp Med. 1984 Jan 1;159(1):193–207. doi: 10.1084/jem.159.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Veillette A., Bookman M. A., Horak E. M., Samelson L. E., Bolen J. B. Signal transduction through the CD4 receptor involves the activation of the internal membrane tyrosine-protein kinase p56lck. Nature. 1989 Mar 16;338(6212):257–259. doi: 10.1038/338257a0. [DOI] [PubMed] [Google Scholar]
  34. Weinhold K. J., Lyerly H. K., Stanley S. D., Austin A. A., Matthews T. J., Bolognesi D. P. HIV-1 GP120-mediated immune suppression and lymphocyte destruction in the absence of viral infection. J Immunol. 1989 May 1;142(9):3091–3097. [PubMed] [Google Scholar]
  35. Weyand C. M., Goronzy J., Fathman C. G. Modulation of CD4 by antigenic activation. J Immunol. 1987 Mar 1;138(5):1351–1354. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES