The Role of Granzyme B in Cytotoxic T Lymphocyte Assisted Suicide

  • R. Chris Bleackley


Two branches have evolved in the immune system to recognize foreign molecules and thus protect against pathogens. In humoral immunity, antibodies are produced that bind to these specific structures and hence stimulate their removal by phagocytosis or complement mediated lysis. T lymphocytes have on their surface a receptor that, like antibodies, binds to foreign peptides presented in the context of the major histocompatibility proteins. As a result the effectors of cell mediated immunity, the cytotoxic T lymphocytes, become activated and can then recognize and destroy any antigen expressing pathogenic cell. This branch of the immune system is particularly involved in the eradication of virus infected cells, but also may play a role in lysis of tumors, transplanted cells and in the destruction of normal host cells in autoimmune disorders.


Serine Protease Assisted Suicide Complement Mediate Lysis Serine Esterase Serine Protease Gene 
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. Babichuk, C.K., B.L. Duggan & R.C. Bleackley. In vivo regulation of murine granzyme B gene transcription in activated primary T cells. J. Biol. Chem. 271:16485–16493 (1996).PubMedCrossRefGoogle Scholar
  2. Bleackley, R.C., C.G. Lobe, B. Duggan, N. Ehrman, C. Fregeau, M. Meier, M. Letellier, C. Havele, J. Shaw & V. Paetkau. The isolation and characterization of a family of serine protease genes expressed inactivated cytotoxic T lymphocytes. Immunological Reviews 103:5–19 (1988a).PubMedCrossRefGoogle Scholar
  3. Bleackley, R.C., B. Duggan, N. Ehrman & C.G. Lobe. Isolation of two cDNA sequences which encode cytotoxic cell proteases. FEBS Lett. 234:153–159 (1988b).PubMedCrossRefGoogle Scholar
  4. Caputo, A., M.N.G. James, J.C. Powers, D. Hudig & R.C. Bleackley. Conversion of the substrate specificity of mouse proteinase granzyme B. Nature Structural Biology 1:364–367 (1994).PubMedCrossRefGoogle Scholar
  5. Caputo, A., R.S. Garner, U. Winkler, D. Hudig & R.C. Bleackley. Activation of recombinant murine cytotoxic cell proteinase-1 requires deletion of an amino-terminal dipeptide. J. Biol. Chem. 268:17672–17675 (1993).PubMedGoogle Scholar
  6. Crosby, J.L., R.C. Bleackley & J.H. Nadeau. A complex of serine protease genes expressed preferentially in cytotoxic T-lymphocytes is closely linked to the T-cell receptor å and_-chain genes on mouse chromosome 14. Genomics 6:252–259 (1990).PubMedCrossRefGoogle Scholar
  7. Darmon, A. & R.C. Bleackley. An ICE-like protease is a key component of fas-mediated apoptosis. J. Biol. Chem. 00:000–000 (1996). (in press).Google Scholar
  8. Darmon, A.J., D.W. Nicholson & R.C. Bleackley. Activation of the apoptotic protease CPP32 by cytotoxic T-cellderived granzyme B. Nature 377:446–448 (1995).PubMedCrossRefGoogle Scholar
  9. Darmon, A.J., N. Ehrman, A. Caputo, J. Fujinaga & R.C. Bleackley. The cytotoxic T cell proteinase granzyme B does not activate interleukin-l_-converting enzyme. J. Biol. Chem. 269:32043–32046 (1994).PubMedGoogle Scholar
  10. Darmon, A.J., T.J. Ley, D.W. Nicholson & R.C. Bleackley. Cleavage of CPP32 by granzyme B represents a nonredundant role for granzyme B in the induction of target cell DNA fragmentation. J. Biol. Chem. 00:000–000 (1996). (in press).Google Scholar
  11. Duke, R.C., P.M. Persechini, S. Chang, C.-C. Liu, J.J. Cohen & J.D.-E. Young. Purified perforin induces target cell lysis but not DNA fragmentation. J. Exp. Med., 170:1451–1456 (1989).PubMedCrossRefGoogle Scholar
  12. Frégeau, C.J. & R.C. Bleackley. Transcription of two cytotoxic cell protease genes is under the control of different regulatory elements. Nucleic Acids Research 19:5583–5590 (1991).PubMedCrossRefGoogle Scholar
  13. Garner, R., C.D. Helgason, E.A. Atkinson, M.J. Pinkoski, H.L. Ostergaard, O. Sorensen, A. Fu, P.H. Lapchak, A. Rabinovitch, J.E. McElhaney, G. Berke & R.C. Bleackley. Characterization of a granule-independent lytic mechanism used by CTL hybridomas. J. Immunol. 153:5413–5421 (1994).PubMedGoogle Scholar
  14. Gershenfeld, H.K. & I.L. Weissman. Cloning of a cDNA for a T cell-specific serine protease from a cytotoxic T lymphocyte. Science 232:854–858 (1986).PubMedCrossRefGoogle Scholar
  15. Gu, Y., C. Sarnecki, M.A. Fleming, J.A. Lippke, R.C. Bleackley & M.S.-S. Su. Processing and activation of CMH-1 by granzyme B. J. Biol. Chem. 271:10816–10820 (1996).PubMedCrossRefGoogle Scholar
  16. Helgason, C.D., J.A. Prendergast, G. Berke & R.C Bleackley. Peritoneal exudate lymphocyte and mixed lymphocyte culture hybridomas are cytolytic in the absence of cytotoxic cell protease and perforin. Eur. J. Immunol. 22:3187–3190(1992).PubMedCrossRefGoogle Scholar
  17. Henkart, M.P. & P.A. Henkart. Lymphocyte mediated cytolysis as a secretory phenomenon. Adv. Exp. Med. Biol. 146:227–247(1982).PubMedCrossRefGoogle Scholar
  18. Lipman, M.L., A.C. Stevens, R.C. Bleackley, H. Helderman, T.R. McCune, W.H. Harmon, M.E. Shapiro, S. Rosen & T.B. Strom. The strong correlation of cytotoxic T lymphocyte-specific serine protease gene transcripts with renal allograft rejection. Transplantation 53:73–79 (1992).PubMedCrossRefGoogle Scholar
  19. Lobe, C.G., C. Havele & R.C. Bleackley. Cloning of two genes which are specifically expressed in activated cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 83:1448–1452 (1986a).PubMedCrossRefGoogle Scholar
  20. Lobe, C.G., B. Finlay, W. Paranchych, V.H. Paetkau & R.C. Bleackley. Two cytotoxic T lymphocyte-specific genes encode unique serine proteases. Science 232:858–861 (1986b).PubMedCrossRefGoogle Scholar
  21. Lobe, C.G., J. Shaw, C Fregeau, B. Duggan, M. Meier, A. Brewer, C Upton, G. McFadden, R.K. Patient, V.H. Paetkau & R.C Bleackley. Transcriptional regulation of two cytotoxic T lymphocyte-specific serine protease genes. Nucleic Acids Research 17:5765–5779 (1989).PubMedCrossRefGoogle Scholar
  22. Mueller, C., H.K. Gershenfeld, CG. Lobe, C.Y. Okada, R.C. Bleackley & I.L. Weissman. Expression of two serine esterase genes during an allograft rejection in the mouse. Transplantation Proc. (1988).Google Scholar
  23. Murphy, M.E.P., J. Moult, R.C Bleackley, I.L. Weissman & M.N.G. James. Comparative molecular model building of two serine proteinases from cytotoxic T lymphocytes. Proteins: Structure, Function and Genetics 4:190–204(1988).CrossRefGoogle Scholar
  24. Pinkoski, M.J., U. Winkler, D. Hudig & R.C. Bleackley. Binding of granzyme B in the nucleus of target cells: Recognition of an 80 kDa protein. J. Biol. Chem. 271:10225–10229 (1996).PubMedCrossRefGoogle Scholar
  25. Prendergast, J.A., CD. Helgason & R.C Bleackley. Quantitative polymerase chain reaction analysis of cytotoxic cell proteinase gene transcripts in T cells — pattern of expression is dependent on the nature of the stimulus. J. Biol. Chem. 267:5090–5095 (1992).PubMedGoogle Scholar
  26. Prendergast, J.A., M. Pinkoski, A. Wolfenden & R.C. Bleackley. Structure and evolution of the cytotoxic cell proteinase genes CCP3, CCP4 and CCP5. J. Mol Biol. 220:867–875 (1991).PubMedCrossRefGoogle Scholar
  27. Redmond, M.J., M. Letellier, J.M.R. Parker, C. Lobe, C Havele, V. Paetkau & R.C. Bleackley. A serine protease (CCP1) is sequestered in the cytoplasmic granules of cytotoxic T lymphocytes. J. Immunol. 139:3184–3188(1987).PubMedGoogle Scholar
  28. Shi, L., C.-M. Kam, J.C Powers, R. Aebersold & A.H. Greenberg. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. J. Exp. Med. 176:1521–1529(1992).PubMedCrossRefGoogle Scholar
  29. Yuan, J., S. Shaham, S. Ledoux, H.M. Ellis & H.R. Horvitz. The C elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1B-converting enzyme. Cell 75:641–652 (1993).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • R. Chris Bleackley
    • 1
  1. 1.Department of BiochemistryUniversity of AlbertaEdmontonCanada

Personalised recommendations