Mechanism of T-Dependent Cytotoxicity: Role of Papain-Sensitive Non Class I MHC Target Molecules and Expression of Target Antigen for Cytotoxicity

  • Benjamin Bonavida
  • Hanna Ostergaard
  • Jonathan Katz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 187)


Cell mediated cytotoxicity (CMC) has been shown to play a major role in resistance to viral infections, tumor rejection and allograft rejection. The mechanism by which the cytotoxic phenomenon operates has been the subject of many investigations, but still remains elusive. Several approaches have been used, such as chemical inhibitors which allow for the dissection of lysis into three steps, namely, binding and/or recognition, programming for lysis, and the killer cell independent lysis stage (1). Other approaches have made use of blocking antibodies which allow for the characterization of surface molecules involved in lysis (2). These studies suggest that lysis is a complex phenomenon requiring several interactions between the lymphocyte and the target cell before lysis is achieved. The nature of these interactions and the biochemical nature of the molecules involved has been studied in part. For instance, it is clear that H2 antigens on target cells are recognized by the CTL receptor. Likewise, several molecular species on CTL have also been implicated in cytotolysis such as Lyt23 and the LFA family of molecules (3–5).


Target Cell Effector Cell Sodium Periodate 51Cr Release Target Cell Membrane 
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  1. 1.
    E. Martz, Mechanism of specific tumor cell lysis by alloimmune T lymphocytes. Resolution and characterization of discrete steps in the cellular interaction. Contemp. Topics Immunobiol. 7:301 (1977).CrossRefGoogle Scholar
  2. 2.
    J. Fan and B. Bonavida, Studies on the induction and expression of T-cell mediated immunity XIV. Role of Lyt-2 antigens of CTL and H2 antigens of target cells on antigen non-specific oxidation dependent cellular cytotoxicity (ODCC) mediated by sodium periodate oxidation of either effector or target cells. J. Immunol. 131:1426 (1983).PubMedGoogle Scholar
  3. 3.
    B. Bonavida, T. P. Bradley, J. Fan, R. Effros, J. R. Hiserodt, and H. Wexler, Molecular interactions in T-cell mediated cytotoxicity. Immunol. Rev. 72:119 (1983).PubMedCrossRefGoogle Scholar
  4. 4.
    E. Martz, W. Heagy, and S. H. Gromkowski, The mechanism of CTL-mediated killing: monoclonal antibody analysis of the roles of killer and target cell membrane proteins. Immunol. Rev. 72:73 (1983).PubMedCrossRefGoogle Scholar
  5. 5.
    T. A. Springer, D. Davignon, M. Y. Ho, K. Kurzinger, E. Martz, and F. Sanchez-Madrid, LFA-1 and Lyt-2,3 molecules associated with T lymphocyte-mediated killing: and Mac-1, and LFA-1 homologue associated with complement receptor function. Immunol. Rev. 68:171 (1982).PubMedCrossRefGoogle Scholar
  6. 6.
    M. J. Bevan and M. Cohn, Cytotoxic effects of antigen-and mitogen-induced T cells on various targets. J. Immunol. 114:559 (1975).PubMedGoogle Scholar
  7. 7.
    A. Novogrodsky, Induction of lymphocyte cytotoxicity by modification of the effector or target cells with periodate or with neuraminidase and galactose oxidase. J. Immunol. 114:1089 (1975).PubMedGoogle Scholar
  8. 8.
    B. Bonavida and T. P. Bradley, Studies on the induction and expression of T-cell mediated immunity. V. Lectin-induced nonspecific cell-mediated cytotoxicity by alloimmune lymphocytes. Transplantation 21:94 (1976).PubMedCrossRefGoogle Scholar
  9. 9.
    B. Bonavida, A. Robins, and A. Saxon, Lectin-dependent cellular cytotoxicity in man. Transplantation 23:261 (1977).PubMedCrossRefGoogle Scholar
  10. 10.
    T. P. Bradley and B. Bonavida, Mechanism of cell-mediated cytotoxicity at the single cell level. V. The importance of target cell structures in cytotoxic T-lymphocyte mediated antigen non-specific lectin-dependent cellular cytotoxicity. J. Immunol. 129:2352 (1982).PubMedGoogle Scholar
  11. 11.
    G. Berke, H. E. Mcvey, and W. R. Clark, T-lymphocyte mediated cytoloysis. I. One common mechanism for target recognition in specific and lectin-dependent cytolysis. J. Immunol. 127:776 (1982).Google Scholar
  12. 12.
    G. Berke, V. Hu, E. Mcvey, and W. R. Clark, T-lymphocyte-mediated cytolysis. II. Role of target cell histocompatibility antigens in recognition and lysis. J. Immunol. 127:782 (1981).PubMedGoogle Scholar
  13. 13.
    T. P. Bradley and B. Bonavida, Mechanism of cell-mediated cytotoxicity at the single cell level. IV. Natural killing and antibody dependent cellular cytotoxicity can be mediated by the same human effector cell as determined by the two target conjugate assay. J. Immunol. 129:2260 (1982).PubMedGoogle Scholar
  14. 14.
    T. P. Bradley and B. Bonavida, Mechanism of cell-mediated cytotoxicity at the single cell level. VII. Trigger of the lethal hit event is distinct for NK/K and LDCC effector cells as measured in the two target conjugate assay. Cell. Immunol. 83:199 (1984).PubMedCrossRefGoogle Scholar
  15. 15.
    G. Klein, P. Terasaki, R. Billing, Somatic cell hybrids between human lymphoma lines. III. Surface markers. Int. J. Cancer 19:66 (1977).PubMedCrossRefGoogle Scholar
  16. 16.
    M. Jondal, C. Spina, and S. Targan, Human spontaneous killer cells selective for tumor-derived target cells. Nature 272:62 (1978).PubMedCrossRefGoogle Scholar
  17. 17.
    K. Thoma, H. D. Engers, J. -C. Cerottini, and K. T. Brunner, Enzymatic removal of H2 alloantigens from the surface of P815-X2 mouse tumor cells. Eur. J. Immunol. 6:257 (1976).CrossRefGoogle Scholar
  18. 18.
    R. F. Todd, Lymphocyte-mediated cytolysis of allogeneic tumor cells in vitro. III. Enzyme sensitivity of target cell antigens. Cell Immunol. 20:287 (1975).CrossRefGoogle Scholar
  19. 19.
    M. J. Bevan and R. Hyman, The ability of H2+ and H2- cell lines to induce or be lysed by cytotoxic T cells. Immunogenetics 4:7 (1977).CrossRefGoogle Scholar
  20. 20.
    T. Hunig, Monoclonal anti-Lyt2.2 antibody blocks lectin-dependent cellular cytotoxicity of H2 negative target cells. J. Exp. Med. 159:551 (1984).PubMedCrossRefGoogle Scholar
  21. 21.
    S. H. Gromkowski, W. Heagy, F. Sanchez-Madrid, T. A. Springer, and E. Martz, Blocking of CTL-mediated killing by monoclonal antibodies to LFA-1 and Lyt-2,3. I. Increased susceptibility to blocking after papain treatment of target cells. J. Immunol. 130:2546 (1983).PubMedGoogle Scholar
  22. 22.
    S. H. Gromkowski, W. Heagy, and E. Martz, Blocking of CTL-mediated killing by monoclonal antibodies to LFA-1 and Lyt-2,3. II. Evidence that trypsin pretreatment of target cells removes a nort-H2 molecule important in killing. (Submitted for publication.)Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Benjamin Bonavida
    • 1
  • Hanna Ostergaard
    • 1
  • Jonathan Katz
    • 1
  1. 1.Department of Microbiology and ImmunologyUCLA School of MedicineLos AngelesUSA

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