Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1982 Oct 1;95(1):137–143. doi: 10.1083/jcb.95.1.137

Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells

PMCID: PMC2112358  PMID: 6982900

Abstract

Specific binding (conjugation) of cytotoxic T lymphocytes (CTL) to target cells (TC) is the first step in a multistage process ultimately resulting in dissolution of the TC and recycling of the CTL. We examined the position of the microtubule organizing center (MTOC) of immune CTL bound to specific TC. Immunofluorescence labeling of freshly prepared CTL-TC conjugates with tubulin antibodies indicated that the MTOC in essentially all conjugated CTL but not in the conjugated TC were oriented towards the intercellular contact site. This finding was corroborated by electron microscopy examination of CTL-TC conjugates fixed either immediately after conjugation or during the lytic process. Antibody-induced caps of membrane antigens of CTL such as H-2 and Thy 1, did not show a similar relationship to the MTOC. Incubation of CTL- TC conjugates, 10-15 min at room temperature, resulted in an apparent deterioration of the microtubular system of conjugated CTL. It is proposed that the CTL plasma membrane proximal to the MTOC is particularly active in forming stable intercellular contacts, resulting in CTL-TC conjugation, and that subsequent modulation of the microtubular system of the CTL may be related to the cytolytic response and to detachment of the effector cell.

Full Text

The Full Text of this article is available as a PDF (3.1 MB).

Selected References

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

  1. Albrecht-Buehler G., Bushnell A. The orientation of centrioles in migrating 3T3 cells. Exp Cell Res. 1979 Apr;120(1):111–118. doi: 10.1016/0014-4827(79)90542-1. [DOI] [PubMed] [Google Scholar]
  2. Albrecht-Buehler G. Does the geometric design of centrioles imply their function? Cell Motil. 1981;1(2):237–245. doi: 10.1002/cm.970010206. [DOI] [PubMed] [Google Scholar]
  3. Berke G., Hu V., McVey E., Clark W. R. T lymphocyte-mediated cytolysis. I. A common mechanism for target recognition in specific and lectin-dependent cytolysis. J Immunol. 1981 Aug;127(2):776–781. [PubMed] [Google Scholar]
  4. Berke G. Interaction of cytotoxic T lymphocytes and target cells. Prog Allergy. 1980;27:69–133. [PubMed] [Google Scholar]
  5. Berke G., McVey E., Hu V., Clark W. R. T lymphocyte-mediated cytolysis. II. Role of target cell histocompatibility antigens in recognition and lysis. J Immunol. 1981 Aug;127(2):782–787. [PubMed] [Google Scholar]
  6. Berke G., Sullivan K. A., Amos B. Rejection of ascites tumor allografts. I. Isolation, characterization, and in vitro reactivity of peritoneal lymphoid effector cells from BALB-c mice immune to EL4 leukosis. J Exp Med. 1972 Jun 1;135(6):1334–1350. doi: 10.1084/jem.135.6.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bourguignon L. Y., Singer S. J. Transmembrane interactions and the mechanism of capping of surface receptors by their specific ligands. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5031–5035. doi: 10.1073/pnas.74.11.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bykovskaja S. N., Rytenko A. N., Rauschenbach M. O., Bykovsky A. F. Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells. I. Hypertrophy and change of orientation of the Golgi apparatus. Cell Immunol. 1978 Sep 15;40(1):164–174. doi: 10.1016/0008-8749(78)90324-6. [DOI] [PubMed] [Google Scholar]
  9. Bykovskaja S. N., Rytenko A. N., Rauschenbach M. O., Bykovsky A. F. Ultrastructural alteration of cytolytic T lymphocytes following their interaction with target cells. II. Morphogenesis of secretory granules and intracellular vacuoles. Cell Immunol. 1978 Sep 15;40(1):175–185. doi: 10.1016/0008-8749(78)90325-8. [DOI] [PubMed] [Google Scholar]
  10. Canty T. G., Wunderlich J. R. Quantitative in vitro assay of cytotoxic cellular immunity. J Natl Cancer Inst. 1970 Oct;45(4):761–772. [PubMed] [Google Scholar]
  11. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  12. Fishelson Z., Berke G. T lymphocyte-mediated cytolysis: dissociation of the binding and lytic mechanisms of the effector cell. J Immunol. 1978 Apr;120(4):1121–1126. [PubMed] [Google Scholar]
  13. Flanagan J., Koch G. L. Cross-linked surface Ig attaches to actin. Nature. 1978 May 25;273(5660):278–281. doi: 10.1038/273278a0. [DOI] [PubMed] [Google Scholar]
  14. Geiger B., Singer S. J. Association of microtubules and intermediate filaments in chicken gizzard cells as detected by double immunofluorescence. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4769–4773. doi: 10.1073/pnas.77.8.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Golstein P. Sensitivity of cytotoxic T cells to T-cell mediated cytotoxicity. Nature. 1974 Nov 1;252(5478):81–83. doi: 10.1038/252081a0. [DOI] [PubMed] [Google Scholar]
  16. Golstein P., Smith E. T. Mechanism of T-cell-mediated cytolysis: the lethal hit stage. Contemp Top Immunobiol. 1977;7:273–300. doi: 10.1007/978-1-4684-3054-7_8. [DOI] [PubMed] [Google Scholar]
  17. Henney C. S. T-Cell-mediated cytolysis: an overview of some current issues. Contemp Top Immunobiol. 1977;7:245–272. doi: 10.1007/978-1-4684-3054-7_7. [DOI] [PubMed] [Google Scholar]
  18. Malech H. L., Root R. K., Gallin J. I. Structural analysis of human neutrophil migration. Centriole, microtubule, and microfilament orientation and function during chemotaxis. J Cell Biol. 1977 Dec;75(3):666–693. doi: 10.1083/jcb.75.3.666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marshak-Rothstein A., Fink P., Gridley T., Raulet D. H., Bevan M. J., Gefter M. L. Properties and applications of monoclonal antibodies directed against determinants of the Thy-1 locus. J Immunol. 1979 Jun;122(6):2491–2497. [PubMed] [Google Scholar]
  20. Martz E. Mechanism of specific tumor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaction. Contemp Top Immunobiol. 1977;7:301–361. doi: 10.1007/978-1-4684-3054-7_9. [DOI] [PubMed] [Google Scholar]
  21. Pollard T. D., Weihing R. R. Actin and myosin and cell movement. CRC Crit Rev Biochem. 1974 Jan;2(1):1–65. doi: 10.3109/10409237409105443. [DOI] [PubMed] [Google Scholar]
  22. Rosen D., Fishelson Z., Berke G. The role of cytotoxic T lymphocyte projections in target cell lysis. Transplant Proc. 1981 Mar;13(1 Pt 2):1073–1078. [PubMed] [Google Scholar]
  23. Ryser J. E., Rungger-Brändle E., Chaponnier C., Gabbiani G., Vassalli P. The area of attachment of cytotoxic T lymphocytes to their target cells shows high motility and polarization of actin, but not myosin. J Immunol. 1982 Mar;128(3):1159–1162. [PubMed] [Google Scholar]
  24. Sanderson C. J., Glauert A. M. The mechanism of T-cell mediated cytotoxicity. VI. T-cell projections and their role in target cell killing. Immunology. 1979 Jan;36(1):119–129. [PMC free article] [PubMed] [Google Scholar]
  25. Sanderson C. J. The mechanism of lymphocyte-mediated cytotoxicity. Biol Rev Camb Philos Soc. 1981 May;56(2):153–197. doi: 10.1111/j.1469-185x.1981.tb00346.x. [DOI] [PubMed] [Google Scholar]
  26. Schreiner G. F., Unanue E. R. Membrane and cytoplasmic changes in B lymphocytes induced by ligand-surface immunoglobulin interaction. Adv Immunol. 1976;24:37–165. doi: 10.1016/s0065-2776(08)60329-6. [DOI] [PubMed] [Google Scholar]
  27. Stackpole C. W., Jacobson J. B., Lardis M. P. Two distinct types of capping of surface receptors on mouse lymphoid cells. Nature. 1974 Mar 15;248(445):232–234. doi: 10.1038/248232a0. [DOI] [PubMed] [Google Scholar]
  28. Tilney L. G., Gibbins J. R. Microtubules in the formation and development of the primary mesenchyme in Arbacia punctulata. II. An experimental analysis of their role in development and maintenance of cell shape. J Cell Biol. 1969 Apr;41(1):227–250. doi: 10.1083/jcb.41.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Toh B. H., Hard C. C. Actin co-caps with concanavalin A receptors. Nature. 1977 Oct 20;269(5630):695–697. doi: 10.1038/269695a0. [DOI] [PubMed] [Google Scholar]
  30. Unanue E. R., Perkins W. D., Karnovsky M. J. Ligand-induced movement of lymphocyte membrane macromolecules. I. Analysis by immunofluorescence and ultrastructural radioautography. J Exp Med. 1972 Oct 1;136(4):885–906. doi: 10.1084/jem.136.4.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yahara I., Edelman G. M. Modulation of lymphocyte receptor mobility by concanavalin A and colchicine. Ann N Y Acad Sci. 1975 Jun 30;253:455–469. doi: 10.1111/j.1749-6632.1975.tb19221.x. [DOI] [PubMed] [Google Scholar]
  32. Yahara I., Edelman G. M. Restriction of the mobility of lymphocyte immunoglobulin receptors by concanavalin A. Proc Natl Acad Sci U S A. 1972 Mar;69(3):608–612. doi: 10.1073/pnas.69.3.608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yakara I., Kakimoto-Sameshima F. Microtubule organization of lymphocytes and its modulation by patch and cap formation. Cell. 1978 Sep;15(1):251–259. doi: 10.1016/0092-8674(78)90100-9. [DOI] [PubMed] [Google Scholar]
  34. Zagury D., Bernard J., Jeannesson P., Thiernesse N., Cerottini J. C. Studies on the mechanism of T cell-mediated lysis at the single effector cell level. I. Kinetic analysis of lethal hits and target cell lysis in multicellular conjugates. J Immunol. 1979 Oct;123(4):1604–1609. [PubMed] [Google Scholar]
  35. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  36. de Petris S., Raff M. C. Distribution of immunoglobulin on the surface of mouse lymphoid cells as determined by immunoferritin electron microscopy. Antibody-induced, temperature-dependent redistribution and its implications for membrane structure. Eur J Immunol. 1972 Dec;2(6):523–535. doi: 10.1002/eji.1830020611. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES