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J Exp Med. Mar 1, 1986; 163(3): 489–498.
PMCID: PMC2188060

On the mechanism of unidirectional killing in mixtures of two cytotoxic T lymphocytes. Unidirectional polarization of cytoplasmic organelles and the membrane-associated cytoskeleton in the effector cell

Abstract

In mixtures of two CTL of the type a anti-b and b anti-c, only the latter is lysed; i.e., killing is unidirectional. Here, we show that two profound types of changes occur in the effector CTL but not in the target CTL upon formation of couples between them. One is that the microtubule organizing center (and presumably the Golgi apparatus that is invariably colocalized with it) is reoriented inside the effector CTL to face the bound target CTL. This unidirectional reorientation, it is proposed, serves to direct putative cytotoxic secretory components derived from the Golgi apparatus of the effector cell to the site of cell-cell binding. The second unidirectional change is in the membrane- associated cytoskeleton of the effector CTL in the area of target cell binding. The cytoskeletal protein talin, but not any of four other such proteins assayed, is highly concentrated at the contacting membrane of the effector CTL, while it is uniformly distributed over the entire membrane of the bound target CTL. This localized, massive cytoskeletal reorganization may reflect a mechanism to protect the membrane of the effector CTL from the effects of putative cytotoxic components secreted by the effector cell into the intercellular space between it and the target cell.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Berke G. Cytotoxic T-lymphocytes. How do they function? Immunol Rev. 1983;72:5–42. [PubMed]
  • Rothstein TL, Mage M, Jones G, McHugh LL. Cytotoxic T lymphocyte sequential killing of immobilized allogeneic tumor target cells measured by time-lapse microcinematography. J Immunol. 1978 Nov;121(5):1652–1656. [PubMed]
  • Kuppers RC, Henney CS. Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells. J Immunol. 1977 Jan;118(1):71–76. [PubMed]
  • Dennert G, Podack ER. Cytolysis by H-2-specific T killer cells. Assembly of tubular complexes on target membranes. J Exp Med. 1983 May 1;157(5):1483–1495. [PMC free article] [PubMed]
  • Kupfer A, Dennert G, Singer SJ. Polarization of the Golgi apparatus and the microtubule-organizing center within cloned natural killer cells bound to their targets. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7224–7228. [PMC free article] [PubMed]
  • Kupfer A, Dennert G. Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells. J Immunol. 1984 Nov;133(5):2762–2766. [PubMed]
  • Kupfer A, Dennert G, Singer SJ. The reorientation of the Golgi apparatus and the microtubule-organizing center in the cytotoxic effector cell is a prerequisite in the lysis of bound target cells. J Mol Cell Immunol. 1985;2(1):37–49. [PubMed]
  • Henkart PA, Millard PJ, Reynolds CW, Henkart MP. Cytolytic activity of purified cytoplasmic granules from cytotoxic rat large granular lymphocyte tumors. J Exp Med. 1984 Jul 1;160(1):75–93. [PMC free article] [PubMed]
  • Podack ER, Konigsberg PJ. Cytolytic T cell granules. Isolation, structural, biochemical, and functional characterization. J Exp Med. 1984 Sep 1;160(3):695–710. [PMC free article] [PubMed]
  • Berlin RD, Oliver JM. Analogous ultrastructure and surface properties during capping and phagocytosis in leukocytes. J Cell Biol. 1978 Jun;77(3):789–804. [PMC free article] [PubMed]
  • Ryser JE, 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]
  • Carpén O, Virtanen I, Lehto VP, Saksela E. Polarization of NK cell cytoskeleton upon conjugation with sensitive target cells. J Immunol. 1983 Dec;131(6):2695–2698. [PubMed]
  • Lazarides E, Burridge K. Alpha-actinin: immunofluorescent localization of a muscle structural protein in nonmuscle cells. Cell. 1975 Nov;6(3):289–298. [PubMed]
  • Geiger B. A 130K protein from chicken gizzard: its localization at the termini of microfilament bundles in cultured chicken cells. Cell. 1979 Sep;18(1):193–205. [PubMed]
  • Geiger B, Tokuyasu KT, Dutton AH, Singer SJ. Vinculin, an intracellular protein localized at specialized sites where microfilament bundles terminate at cell membranes. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4127–4131. [PMC free article] [PubMed]
  • Burridge K, Connell L. A new protein of adhesion plaques and ruffling membranes. J Cell Biol. 1983 Aug;97(2):359–367. [PMC free article] [PubMed]
  • Maher P, Singer SJ. A 200-kd protein isolated from the fascia adherens membrane domains of chicken cardiac muscle cells is detected immunologically in fibroblast focal adhesions. Cell Motil. 1983;3(5-6):419–429. [PubMed]
  • Bretscher A, Weber K. Fimbrin, a new microfilament-associated protein present in microvilli and other cell surface structures. J Cell Biol. 1980 Jul;86(1):335–340. [PMC free article] [PubMed]
  • Geiger B, Singer SJ. The participation of alpha-actinin in the capping of cell membrane components. Cell. 1979 Jan;16(1):213–222. [PubMed]
  • Kupfer A, Louvard D, Singer SJ. Polarization of the Golgi apparatus and the microtubule-organizing center in cultured fibroblasts at the edge of an experimental wound. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2603–2607. [PMC free article] [PubMed]
  • Rogalski AA, Singer SJ. Associations of elements of the Golgi apparatus with microtubules. J Cell Biol. 1984 Sep;99(3):1092–1100. [PMC free article] [PubMed]
  • Abercrombie M, Heaysman JE, Pegrum SM. The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella. Exp Cell Res. 1971 Aug;67(2):359–367. [PubMed]

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