Skip to main content
NCBI 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
. 1992 Sep 1;89(17):8035–8039. doi: 10.1073/pnas.89.17.8035

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

N Oyaizu 1, N Chirmule 1, H Yagura 1, R Pahwa 1, R A Good 1, S Pahwa 1
PMCID: PMC49850  PMID: 1355602

Abstract

The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor beta-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor alpha-chain expression, stimulation with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.

Full text

PDF
8035

Selected References

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

  1. 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]
  2. Cammarota G., Scheirle A., Takacs B., Doran D. M., Knorr R., Bannwarth W., Guardiola J., Sinigaglia F. Identification of a CD4 binding site on the beta 2 domain of HLA-DR molecules. Nature. 1992 Apr 30;356(6372):799–801. doi: 10.1038/356799a0. [DOI] [PubMed] [Google Scholar]
  3. Chatila T., Wood N., Parsonnet J., Geha R. S. Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells. J Immunol. 1988 Feb 15;140(4):1250–1255. [PubMed] [Google Scholar]
  4. Chirmule N., Kalyanaraman V. S., Oyaizu N., Slade H. B., Pahwa S. Inhibition of functional properties of tetanus antigen-specific T-cell clones by envelope glycoprotein GP120 of human immunodeficiency virus. Blood. 1990 Jan 1;75(1):152–159. [PubMed] [Google Scholar]
  5. Dianzani U., Shaw A., al-Ramadi B. K., Kubo R. T., Janeway C. A., Jr Physical association of CD4 with the T cell receptor. J Immunol. 1992 Feb 1;148(3):678–688. [PubMed] [Google Scholar]
  6. Doyle C., Strominger J. L. Interaction between CD4 and class II MHC molecules mediates cell adhesion. Nature. 1987 Nov 19;330(6145):256–259. doi: 10.1038/330256a0. [DOI] [PubMed] [Google Scholar]
  7. Fleischer B., Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med. 1988 May 1;167(5):1697–1707. doi: 10.1084/jem.167.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frank S. J., Niklinska B. B., Orloff D. G., Merćep M., Ashwell J. D., Klausner R. D. Structural mutations of the T cell receptor zeta chain and its role in T cell activation. Science. 1990 Jul 13;249(4965):174–177. doi: 10.1126/science.2371564. [DOI] [PubMed] [Google Scholar]
  9. Herman A., Labrecque N., Thibodeau J., Marrack P., Kappler J. W., Sekaly R. P. Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9954–9958. doi: 10.1073/pnas.88.22.9954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Juszczak R. J., Turchin H., Truneh A., Culp J., Kassis S. Effect of human immunodeficiency virus gp120 glycoprotein on the association of the protein tyrosine kinase p56lck with CD4 in human T lymphocytes. J Biol Chem. 1991 Jun 15;266(17):11176–11183. [PubMed] [Google Scholar]
  12. Koning F., Maloy W. L., Coligan J. E. The implications of subunit interactions for the structure of the T cell receptor-CD3 complex. Eur J Immunol. 1990 Feb;20(2):299–305. doi: 10.1002/eji.1830200211. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Liu H., Lampe M. A., Iregui M. V., Cantor H. Conventional antigen and superantigen may be coupled to distinct and cooperative T-cell activation pathways. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8705–8709. doi: 10.1073/pnas.88.19.8705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Manolios N., Bonifacino J. S., Klausner R. D. Transmembrane helical interactions and the assembly of the T cell receptor complex. Science. 1990 Jul 20;249(4966):274–277. doi: 10.1126/science.2142801. [DOI] [PubMed] [Google Scholar]
  17. Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
  18. O'Rourke A. M., Mescher M. F., Webb S. R. Activation of polyphosphoinositide hydrolysis in T cells by H-2 alloantigen but not MLS determinants. Science. 1990 Jul 13;249(4965):171–174. doi: 10.1126/science.2164711. [DOI] [PubMed] [Google Scholar]
  19. Oyaizu N., Chirmule N., Pahwa S. Role of CD4 molecule in the induction of interleukin 2 and interleukin 2 receptor in class II major histocompatibility complex-restricted antigen-specific T helper clones. T cell receptor/CD3 complex transmits CD4-dependent and CD4-independent signals. J Clin Invest. 1992 Jun;89(6):1807–1816. doi: 10.1172/JCI115785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Patarca R., Wei F. Y., Iregui M. V., Cantor H. Differential induction of interferon gamma gene expression after activation of CD4+ T cells by conventional antigen and Mls superantigen. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2736–2739. doi: 10.1073/pnas.88.7.2736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Punt J. A., Kubo R. T., Saito T., Finkel T. H., Kathiresan S., Blank K. J., Hashimoto Y. Surface expression of a T cell receptor beta (TCR-beta) chain in the absence of TCR-alpha, -delta, and -gamma proteins. J Exp Med. 1991 Oct 1;174(4):775–783. doi: 10.1084/jem.174.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Quaratino S., Murison G., Knyba R. E., Verhoef A., Londei M. Human CD4- CD8- alpha beta+ T cells express a functional T cell receptor and can be activated by superantigens. J Immunol. 1991 Nov 15;147(10):3319–3323. [PubMed] [Google Scholar]
  23. Rojo J. M., Janeway C. A., Jr The biologic activity of anti-T cell receptor V region monoclonal antibodies is determined by the epitope recognized. J Immunol. 1988 Feb 15;140(4):1081–1088. [PubMed] [Google Scholar]
  24. Rosenstein Y., Burakoff S. J., Herrmann S. H. HIV-gp120 can block CD4-class II MHC-mediated adhesion. J Immunol. 1990 Jan 15;144(2):526–531. [PubMed] [Google Scholar]
  25. Rudd C. E. CD4, CD8 and the TCR-CD3 complex: a novel class of protein-tyrosine kinase receptor. Immunol Today. 1990 Nov;11(11):400–406. doi: 10.1016/0167-5699(90)90159-7. [DOI] [PubMed] [Google Scholar]
  26. Scholl P. R., Diez A., Geha R. S. Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. J Immunol. 1989 Oct 15;143(8):2583–2588. [PubMed] [Google Scholar]
  27. Spertini F., Spits H., Geha R. S. Staphylococcal exotoxins deliver activation signals to human T-cell clones via major histocompatibility complex class II molecules. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7533–7537. doi: 10.1073/pnas.88.17.7533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sékaly R. P., Croteau G., Bowman M., Scholl P., Burakoff S., Geha R. S. The CD4 molecule is not always required for the T cell response to bacterial enterotoxins. J Exp Med. 1991 Feb 1;173(2):367–371. doi: 10.1084/jem.173.2.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Yagi J., Baron J., Buxser S., Janeway C. A., Jr Bacterial proteins that mediate the association of a defined subset of T cell receptor:CD4 complexes with class II MHC. J Immunol. 1990 Feb 1;144(3):892–901. [PubMed] [Google Scholar]
  32. de la Hera A., Müller U., Olsson C., Isaaz S., Tunnacliffe A. Structure of the T cell antigen receptor (TCR): two CD3 epsilon subunits in a functional TCR/CD3 complex. J Exp Med. 1991 Jan 1;173(1):7–17. doi: 10.1084/jem.173.1.7. [DOI] [PMC free article] [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