Abstract
Cloned allospecific cytolytic T lymphocytes (CTL) adhere to purified class I alloantigen immobilized on plastic and degranulate in response to it. Binding and degranulation are inhibited by drugs that impair cytoskeletal function. Cytochalasins D and E, which interfere with microfilament function, and colchicine, which disrupts microtubules, were used and gave qualitatively similar results. Concentrations of these drugs that inhibited degranulation in response to alloantigen did not inhibit response to immobilized anti-T cell receptor (TCR) antibody. Neither did they inhibit response when alloantigen was co- immobilized with an antibody against class I on the CTL to promote adhesion between the CTL and antigen-bearing surface. Thus, neither transmembrane signal generation via the TCR nor degranulation per se were prevented. Instead, the drugs act to prevent the initial adhesion to alloantigen. CTL binding to alloantigen depends in part on CD8-class I interaction, and adhesion via CD8 is "activated" by crosslinking the TCR with soluble anti-TCR antibody. This adhesion, too, is shown to be cytoskeleton dependent.
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- Bierer B. E., Burakoff S. J. T cell adhesion molecules. FASEB J. 1988 Jul;2(10):2584–2590. doi: 10.1096/fasebj.2.10.2838364. [DOI] [PubMed] [Google Scholar]
- 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]
- Cerottini J. C., Brunner K. T. Reversible inhibition of lymphocyte-mediated cytotoxicity by cytochalasin B. Nat New Biol. 1972 Jun 28;237(78):272–273. doi: 10.1038/newbio237272a0. [DOI] [PubMed] [Google Scholar]
- Detmers P. A., Wright S. D., Olsen E., Kimball B., Cohn Z. A. Aggregation of complement receptors on human neutrophils in the absence of ligand. J Cell Biol. 1987 Sep;105(3):1137–1145. doi: 10.1083/jcb.105.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dustin M. L., Springer T. A. T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1. Nature. 1989 Oct 19;341(6243):619–624. doi: 10.1038/341619a0. [DOI] [PubMed] [Google Scholar]
- Geiger B., Rosen D., Berke G. Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells. J Cell Biol. 1982 Oct;95(1):137–143. doi: 10.1083/jcb.95.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein S. A., Mescher M. F. Cell-sized, supported artificial membranes (pseudocytes): response of precursor cytotoxic T lymphocytes to class I MHC proteins. J Immunol. 1986 Dec 1;137(11):3383–3392. [PMC free article] [PubMed] [Google Scholar]
- Golstein P., Foa C., MacLennan I. C. Mechanism of T cell-mediated cytolysis: the differential impact of cytochalasins at the recognition and lethal hit stages. Eur J Immunol. 1978 May;8(5):302–309. doi: 10.1002/eji.1830080504. [DOI] [PubMed] [Google Scholar]
- Green W. R., Henney C. S. The mechanism of T cell-mediated cytolysis. Crit Rev Immunol. 1981 Feb;1(4):259–286. [PubMed] [Google Scholar]
- Kane K. P., Champoux P., Mescher M. F. Solid-phase binding of class I and II MHC proteins: immunoassay and T cell recognition. Mol Immunol. 1989 Aug;26(8):759–768. doi: 10.1016/0161-5890(89)90036-9. [DOI] [PubMed] [Google Scholar]
- Kane K. P., Goldstein S. A., Mescher M. F. Class I alloantigen is sufficient for cytolytic T lymphocyte binding and transmembrane signaling. Eur J Immunol. 1988 Dec;18(12):1925–1929. doi: 10.1002/eji.1830181209. [DOI] [PubMed] [Google Scholar]
- Kane K. P., Mescher M. F. Antigen recognition by T cells. Quantitative effects of augmentation by antibodies providing accessory interactions. J Immunol. 1990 Feb 1;144(3):824–829. [PubMed] [Google Scholar]
- Kane K. P., Sherman L. A., Mescher M. F. Molecular interactions required for triggering alloantigen-specific cytolytic T lymphocytes. J Immunol. 1989 Jun 15;142(12):4153–4160. [PubMed] [Google Scholar]
- 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] [Google Scholar]
- Kupfer A., Singer S. J. Cell biology of cytotoxic and helper T cell functions: immunofluorescence microscopic studies of single cells and cell couples. Annu Rev Immunol. 1989;7:309–337. doi: 10.1146/annurev.iy.07.040189.001521. [DOI] [PubMed] [Google Scholar]
- Kupfer A., Singer S. J., Dennert G. 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. J Exp Med. 1986 Mar 1;163(3):489–498. doi: 10.1084/jem.163.3.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Martz E. LFA-1 and other accessory molecules functioning in adhesions of T and B lymphocytes. Hum Immunol. 1987 Jan;18(1):3–37. doi: 10.1016/0198-8859(87)90110-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Menon A. K., Holowka D., Webb W. W., Baird B. Cross-linking of receptor-bound IgE to aggregates larger than dimers leads to rapid immobilization. J Cell Biol. 1986 Feb;102(2):541–550. doi: 10.1083/jcb.102.2.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Rourke A. M., Rogers J., Mescher M. F. Activated CD8 binding to class I protein mediated by the T-cell receptor results in signalling. Nature. 1990 Jul 12;346(6280):187–189. doi: 10.1038/346187a0. [DOI] [PubMed] [Google Scholar]
- Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
- Oliver J. M., Seagrave J., Stump R. F., Pfeiffer J. R., Deanin G. G. Signal transduction and cellular response in RBL-2H3 mast cells. Prog Allergy. 1988;42:185–245. [PubMed] [Google Scholar]
- Pasternack M. S., Eisen H. N. A novel serine esterase expressed by cytotoxic T lymphocytes. 1985 Apr 25-May 1Nature. 314(6013):743–745. doi: 10.1038/314743a0. [DOI] [PubMed] [Google Scholar]
- Patarroyo M., Jondal M., Gordon J., Klein E. Characterization of the phorbol 12,13-dibutyrate (P(Bu)2) induced binding between human lymphocytes. Cell Immunol. 1983 Oct 15;81(2):373–383. doi: 10.1016/0008-8749(83)90244-7. [DOI] [PubMed] [Google Scholar]
- Perez P., Bluestone J. A., Stephany D. A., Segal D. M. Quantitative measurements of the specificity and kinetics of conjugate formation between cloned cytotoxic T lymphocytes and splenic target cells by dual parameter flow cytometry. J Immunol. 1985 Jan;134(1):478–485. [PubMed] [Google Scholar]
- Plaut M., Lichtenstein L. M., Henney C. S. Studies on the mechanism of lymphocyte-mediated cytolysis. 3. The role of microfilaments and microtubules. J Immunol. 1973 Mar;110(3):771–780. [PubMed] [Google Scholar]
- Rothlein R., Springer T. A. The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester. J Exp Med. 1986 May 1;163(5):1132–1149. doi: 10.1084/jem.163.5.1132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staerz U. D., Rammensee H. G., Benedetto J. D., Bevan M. J. Characterization of a murine monoclonal antibody specific for an allotypic determinant on T cell antigen receptor. J Immunol. 1985 Jun;134(6):3994–4000. [PubMed] [Google Scholar]
- Stallcup K. C., Springer T. A., Mescher M. F. Characterization of an anti-H-2 monoclonal antibody and its use in large-scale antigen purification. J Immunol. 1981 Sep;127(3):923–930. [PubMed] [Google Scholar]
- Strom T. B., Garovoy M. R., Carpenter D. B., Merrill J. P. Microtubule function in immune and nonimmune lymphocyte-mediated cytotoxicity. Science. 1973 Jul 13;181(4095):171–173. doi: 10.1126/science.181.4095.171. [DOI] [PubMed] [Google Scholar]
- Takayama H., Trenn G., Humphrey W., Jr, Bluestone J. A., Henkart P. A., Sitkovsky M. V. Antigen receptor-triggered secretion of a trypsin-type esterase from cytotoxic T lymphocytes. J Immunol. 1987 Jan 15;138(2):566–569. [PubMed] [Google Scholar]
- Zagury D. Direct analysis of individual killer T cells: susceptibility of target cells to lysis and secretion of hydrolytic enzymes by CTL. Adv Exp Med Biol. 1982;146:149–169. doi: 10.1007/978-1-4684-8959-0_10. [DOI] [PubMed] [Google Scholar]
- van Kooyk Y., van de Wiel-van Kemenade P., Weder P., Kuijpers T. W., Figdor C. G. Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes. Nature. 1989 Dec 14;342(6251):811–813. doi: 10.1038/342811a0. [DOI] [PubMed] [Google Scholar]
