Human T Lymphocyte Activation

  • Claudio Milanese
  • Robert F. Siliciano
  • Neil E. Richardson
  • Hsiu-Ching Chang
  • Andres Alcover
  • Ellis L. Reinherz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 213)


The T lymphocyte receptor for antigen and histocompatibility molecules is a molecular complex comprised of five polypeptide chains. Both the 49KD alpha and 43KD beta chains are immunoglobulin-like and thus contain variable domains responsible for ligand binding. In contrast, the 20–25KD T3 gamma, delta and epsilon chains are monomorphic structures presumably involved in transmembrane signalling. The alpha and beta subunits are disulfide bonded to each other and held in noncovalent association with the T3 chains. T3-Ti receptor crosslinking leads to conformational modification of a second T lineage specific molecule, termed the 50KD T11 structure and in turn, protein kinase C activation, elevation in intracytoplasmic free calcium and Na+/H+ antiport stimulation.


Major Histocompatibility Complex Phorbol Ester Antigen Receptor Beta Subunit Clonal Proliferation 
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.


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  1. 1.
    B. Benacerraf, and H. O. McDevitt. Histocompatibility linked immune response genes. Science 175:273, (1972).ADSCrossRefGoogle Scholar
  2. 2.
    R. M. Zinkernagel, and P. C. Doherty. H-2 compatibility requirement for T cell mediated lysis of target cells infected with lymphocytic choiromeningitis virus; different cytotoxic T cell specificities are associated with structures coded for in either H-2KI or H-2D. J. Exp. Med. 141:1427, (1975).CrossRefGoogle Scholar
  3. 3.
    O. Acuto, and E. L. Reinherz. The human T cell receptor: Structure and function. N. Engl. J. Med. 312:1100. (1985).CrossRefGoogle Scholar
  4. 4.
    J. Borst, J. E. Colizan, H. Oettgen, S. Pessaro, R. Malin, and C. Terhorst. The human T3/T cell receptor complex: The T3- and T3- subunits are distinct polypeptide chains. Nature 312:455, (1984).ADSCrossRefGoogle Scholar
  5. 5.
    J. M. Kanellopoulos, N. M. Wigglesworth, M. J. Owen, and M. J. Crumpton. Biosynthesis and molecular nature of the T3 antigen of human T lymphocyte. EMBO J. 2:1807, (1983).Google Scholar
  6. 6.
    K. A. Smith, P. E. Baker, S. Gillis, and F. W. Ruscetti. Functional and molecular characteristics of T cell growth factor. Mol. Immunol. 17:579, (1980).CrossRefGoogle Scholar
  7. 7.
    S. C. Meuer, R. E. Hussey, D. A. Cantrell, J. C. Hodgdon, S. F. Schlossman, K. A. Smith, and E. L. Reinherz. Triggering of the T3-Ti antigen receptor complex results in clonal T cell proliferation via an interleukin 2 dependent autocrine pathway. Proc. Natl. Acad. Sci. USA 81:1509, (1984).ADSCrossRefGoogle Scholar
  8. 8.
    J. M. Williams, D. Deloria, J. A. Hansen, C. A. Dinarello, R. Loertscher, H. M. Shapiro, and T. B. Strom. The events of primary T cell activation can be stage by use of Sepharose-bound anti-T3 (64.1) monoclonal antibody and purified interleukin 1. J. Immunol. 135:2249. (1985).Google Scholar
  9. 9.
    D. A. Cantrell, and K. A. Smith. Transient expression of interleukin 2 receptors. Consequences for T cell growth. J. Exp. Med. 158:1895, (1983).CrossRefGoogle Scholar
  10. 10.
    S. C. Meuer, R. E. Hussey, M. Fabbi, D. Fox, O. Acuto, K. A. Fitzgerald, J. C. Hodgdon, J. P. Protentis, S. F. Schlossman, and E. L. Reinherz. An alternative pathway of T cell activation: A functional role for the 50KD T11 sheep erythrocyte receptor. Cell 36:397, (1984).CrossRefGoogle Scholar
  11. 11.
    C. Milanese, N. E. Richardson, and E. L. Reinherz. Identification of a T helper cell derived lymphokine which activates resting T lymphocytes. Science 231:1118, (1986).ADSCrossRefGoogle Scholar
  12. 12.
    E. L. Reinherz, P. C. Kung, G. Goldstein, R. H. Levey, and S. F. Schlossman. Discrete stages of intrathymic differentiation: Analysis of normal thymocytes and leukemic lymphoblasts of T lineage. Proc. Natl. Acad. Sci. USA 77:1588, (1980).ADSCrossRefGoogle Scholar
  13. 13.
    M. M. Davis, Y. S. Chien, N. R. J. Gascoigne, and S. M. Hedrick. A murine T cell receptor gene complex: Isolation structure and rearrangement. Immunol. Rev. 81:235, (1984).CrossRefGoogle Scholar
  14. 14.
    H. D. Royer, O. Acuto, M. Fabbi, R. Tizard, K. Ramachandran, J. Smart, and E. L. Reinherz. Genes encoding the Ti beta subunit of the antigen/MHC receptor undergo rearrangement at a precise stage of intrathymic ontogeny and preceding surface expression of the T3-Ti molecular complex. Cell 39:261, (1984).CrossRefGoogle Scholar
  15. 15.
    H. D. Royer, D. Ramarli, O. Acuto, T. J. Campen, and E. L. Reinherz. Genes encoding the T cell receptor Ti alpha and beta subunits are transcribed in an ordered manner during intrathymic ontogeny. Proc. Natl. Acad. Sci. USA 82:5510, (1985).ADSCrossRefGoogle Scholar
  16. 16.
    D. A. Fox, R. E. Hussey, K. A. Fitzgerald, A. Bensussan, J. F. Daley, S. F. Schlossman, and E. L. Reinherz. Activation of human thymocytes via the 50KD T11 sheep erythrocyte binding protein induces the expression of interleukin 2 receptors on both T3+ and T3- populations. J. Immunol. 134:330, (1985).Google Scholar
  17. 17.
    M. J. Weiss, J. F. Daley, J. C. Hodgdon, and E. L. Reinherz. Calcium dependency of antigen specific (T3-Ti) and alternative (T11) pathways of human T cell activation. Proc. Natl. Acad. Sci. USA 81:6836, (1984).ADSCrossRefGoogle Scholar
  18. 18.
    A. Weiss, D. Imboden, D. Shoback, and J. Stobo. Role of T3 molecules in human T cell activation: T3 dependent activation results in an increase in cytoplasmic free calcium. Proc. Natl. Acad. Sci. USA 81:4169, (1984).ADSCrossRefGoogle Scholar
  19. 19.
    A. Alcover, M. J. Weiss, J. F. Daley, and E. L. Reinherz. The T11 surface glycoprotein is functionally linked to a calcium channel in precursor and mature T lineage cells. Proc. Natl. Acad. Sci. USA (in press).Google Scholar
  20. 20.
    F. Dube, T. Schmidt, C. H. Johnson, and D. Epel. The hierarchy of requirements for an elevated pH during early development of sea urchin embrios. Cell 40:657, (1985).CrossRefGoogle Scholar
  21. 21.
    A. Alcover, C. Milanese, and E. Reinherz. Role of Na+/H+ exchanger in the activation of human lymphocytes. (Submitted).Google Scholar
  22. 22.
    R. F. Siliciano, J. C. Pratt, R. E. Schmidt, J. Ritz, and E. L. Reinherz. Activation of cytolytic T lymphocyte and natural killer cell function through the T11 sheep erythrocyte binding protein. Nature 317:428, (1985).ADSCrossRefGoogle Scholar
  23. 23.
    M. J. Berridge. The molecular basis of communication within the cell. Sci. Amer. 253(4):142, (1985).CrossRefGoogle Scholar
  24. 24.
    J. B. Imboden, and J. D. Stobo. Transmembrane signalling by the T cell antigen receptor. J. Exp. Med. 161:446, (1985).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Claudio Milanese
    • 1
  • Robert F. Siliciano
    • 1
  • Neil E. Richardson
    • 1
  • Hsiu-Ching Chang
    • 1
  • Andres Alcover
    • 1
  • Ellis L. Reinherz
    • 1
  1. 1.Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of MedicineHarvard Medical SchoolBostonUSA

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