Changes in Early and Late Steps of T Cell Activation by WT31 MoAb

  • Sudhir Gupta
  • Makito Shimizu
  • Renu Batra
  • Bharathi Vayuvegula


The induction of T cell activation is usually a consequence of interaction between specific T cell receptors and their ligands. The T cell antigen receptor (TcR) is present on almost all T cells as a heterodimer of α and β glycoprotein (reviewed in 1). The TcR heterodimer is non-covalently associated with CD3 glycoprotein forming a TcR/CD3 complex (1). The TcR is responsible for antigen recognition and the CD3 antigen for signal transduction (reviewed in 2). Recently a monoclonal antibody (MoAb), WT31, has been described that recognizes a framework determinant present on all mature T lymphocytes that express α/β TcR heterodimer (3). In this investigation we have examined the effect of WT31 MoAb on some of the early and late steps of T cell activation to determine whether the WT31 moAb will induce signal transduction and activate human T cells. We show that WT31 activates human T cells via a classical signal transduction pathway.


Phorbol Myristate Acetate Phorbol Myristate Acetate Induce Signal Transduction Cytoplasmic Free Calcium Autologous Mixed Lymphocyte Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Meuer S., Acuto O., Hercend T., Schlossman S. and Reinherz E. The human T-cell receptor. Ann. Rev. Immunol. 2: 23, 1984CrossRefGoogle Scholar
  2. 2.
    Weiss A., Imboden J., Hardy K., Manger B., Terhorst C., and Stobo J. The role of T3/antigen receptor complex in T cell activation. Ann. Rev. Immunol. 4: 593, 1986.CrossRefGoogle Scholar
  3. 3.
    Spitz H., Borst J., Tax W., Capel P.J.A., Terhorst C., and de Vries D.E. Characterstics of a monoclonal antibody (WT31) that recognizes a common epitope on the human T cell receptor for antigen. J. Immunol. 135: 1922–1928, 1985.Google Scholar
  4. 4.
    Smith K.G.C., Austyn J.M., Hariri G., Beverley P.C.L. and Morris P.J. T cell activation by anti-T3 antibodies: Comparision of IgGI and IgG2b switch variants and direct evidence of accessory function of macrophage Fc receptors. Eur. J. Immunol. 16: 478–486, 1986.PubMedCrossRefGoogle Scholar
  5. 5.
    Rinnooy Kan E.A., Platzer E., Welte K., and Wang C.Y. Modulation induction of the T3 antigen by OKT3 antibody is monocyte-dependent. J. Immunol. 133: 2979–2985, 1984.Google Scholar
  6. 6.
    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. 161: 446–456, 1985.PubMedCrossRefGoogle Scholar
  7. 7.
    Imboden J., Weiss A., and Stobo J. The antigen receptor on a human T cell line initiates activation by increasing cytoplasmic free calcium. J. Immunol. 134: 663–665, 1985.PubMedGoogle Scholar
  8. 8.
    Weiss M.J., Daley J.F., Hodgdon J.C., and Reinherz E.L. Calcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation. Proc. Natl. Acad. Sci. (USA) 81: 6836–6340, 1984.CrossRefGoogle Scholar
  9. 9.
    Breitmeyer J.B., Daley J.F., Levine H.B., and Schlossman S. F. The Tl1 (CD2) molecule is functionally linked to the T3/Ti T cell receptor in the majority of T cells. J. Immunol. 139: 2899, 1987.PubMedGoogle Scholar
  10. 10.
    June C.H., Rabinowitch P.S., Ledbetter J.A. CD5 antibodies increase intracellular ionized calcium concentration in T cells. J. Immunol. 138:3299–3305, 1986.Google Scholar
  11. 11.
    Panteleo G.,OliveD., Harris D., Poggi A., Moretta L., and Moretta A. Signal transducing mechanisms involved in human T cell activation via surface T44 molecules. Comparison with signal transduced with the T cell receptor complex. Eur. J. Immunol. 16: 1639, 1986.CrossRefGoogle Scholar
  12. 12.
    Hara T., Fu S.M., and Hansen J.A. Human T cell activation. A new activation pathway used by a major T cell population via disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J. Exp. Med. 161: 1513–1624, 1985.PubMedCrossRefGoogle Scholar
  13. 13.
    Weiss A., Imboden J. Shobach D., and Stobo J. Role of T3 surface molecules in the activation of human T cells: T3-dependent activation results in an increase in cytoplasmic free calcium. Proc. Natl. Acad. Sci. (USA) 81: 4169–4173, 1984.Google Scholar
  14. 14.
    Gupta S., Shimizu M. and Vayuvegula B. T cell activation by antibody (WT31) recognizing q,/ß TcR. (Submitted).Google Scholar
  15. 15.
    Meuer S.D., Hussey R.E., Cantrell D.A., Hodgdon J.C., Schlossman S.F., Smith K.A., and Reinherz E.L. Triggering of the T3-Ti antigen receptor complex results in T cell clonal proliferation through an interleukin 2-dependent autocrine pathway. Proc. Natl. Acad. Sci. (USA) 81: 1719, 1984.CrossRefGoogle Scholar
  16. 16.
    Chandy K.G., DeCoursey T.E., Cahalan M.D., and Gupta S. Electroimmunology: The physiological role of ion channel in the immune system. J. Immunol. 135: 787s - 791s, 1985.PubMedGoogle Scholar
  17. 17.
    DeCoursey T.E., Chandy K.G., Gupta S. and Cahalan M.D. Voltage-gated K channels in human Tlymphocytes. A role in mitogenesis. Nature 307: 465–471, 1984.Google Scholar
  18. 18.
    Cahalan M.D., Chandy K.G., DeCoursey T.E., and Gupta S. A voltage-gated K+ channel in human T lymphocytes. J. Physiol. 358: 468–471, 1985.Google Scholar
  19. 19.
    Matteson D.R. and Deutsch C. K+ channels in T lymphocytes. A patch clamp study using monoclonal antibody adhesion. Nature 307: 468–471, 1984.PubMedCrossRefGoogle Scholar
  20. 20.
    Chandy D.G., DeCoursey T.E., Cahalan M.D., McLaughlin C. and Gupta S. Voltage-gated potassium channels are required for human T lymphocyte activation. J. Exp. Med. 160: 369–385, 1985.CrossRefGoogle Scholar
  21. 21.
    Gupta S. Autologous mixed lymphocyte reaction in man. XVII. In vitro effect of ion channel blocking agents on the autologous mixed lymphocyte reaction. Cell. Immunol. 104:290–295, 1987.Google Scholar
  22. 22.
    Kuno M., Gronzy J., Weyand C.M. and Gardner P. Single channel and whole cell recordings of mitogen-regulated inward currents in human cloned helper T lymphocytes. Nature 323: 269–273, 1986.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Sudhir Gupta
    • 1
  • Makito Shimizu
    • 1
  • Renu Batra
    • 1
  • Bharathi Vayuvegula
    • 1
  1. 1.Division of Basic and Clinical ImmunologyUniversity of CaliforniaIrvineUSA

Personalised recommendations