Abstract
We have previously reported that the murine T cell line EL-4 has an aggregating phenotype, displaying homotypic aggregation (HTA) when exposed to monoclonal antibodies targeting specific cell surface molecules such as leukocyte function-associated antigen-1 (LFA-1). We have used this property of EL-4 cells to isolate additional HTA-inducing MAb by screening a panel of hybridomas that were generated from rats immunized with EL-4 cells. We have isolated a novel anti-Thy-1 MAb (termed FF-10) that is a powerful inducer of HTA in EL-4 cells. In addition to induction of HTA, FF-10 also induces splenocyte proliferation but inhibits anti-CD3-driven T cell proliferation. Thy-1-induced HTA cannot be blocked with MAb targeting intercellular adhesion molecule-1 and -2 (ICAM-1, ICAM-2) or LFA1. Thus, the FF-10 MAb represents a novel and unique tool to investigate the diverse roles of the murine Thy-1 molecule in T cell activation, proliferation and apoptosis.
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References
Reif, A. E., andJ. M. V. Allen. 1964. The AKR thymic antigen and its distribution in leukemias and nervous tissues.J. Exp. Med. 120:413–433.
Crawford, J. M., andR. W. Barton. 1986. Thy-1 glycoprotein: structure, distribution, and ontogeny.Lab. Invest. 54:122–135.
Williams, A. F., andJ. Gagnon. 1982. Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin.Science 216:696–703.
Williams, A. F. 1985. Immunoglobulin-related domains for cell surface recognition.Nature 314:579–580.
Low, M. G., andP. W. Kincade. 1985. Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein.Nature 318:62–64.
Tse, A. G. D., N. Barclay, A. Watts, andA. F. Williams. 1985. A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes.Science 230:1003–1008.
Kroczec, R. A., K. C. Gunter, B. Seligmann, andE. M. Shevach. 1986. Induction of T cell activation by monoclonal anti-Thy-1 antibodies.J. Immunol. 136:4379–4384.
Kroczec, R. A., K. C. Gunter, R. N. Germain, andE. M. Shevach. 1986. Thy-1 functions as a signal transduction molecule in T lymphocytes and transfected B lymphocytes.Nature 322:181–184.
Gunter, K. C., R. N. Germain, R. A. Kroczek, T. Saito, W. M. Yokoyama, C. Chan, A. Weiss, andE. M. Shevach. 1987. Thy-1-mediated T cell activation requires coexpression of CD3/Ti complex.Nature 326:505–507.
Stefanova, I., V. Horejsi, I. J. Ansotegui, W. Knapp, andH. Stockinger. 1991. GPI-anchored cell surface molecules complexed to protein tyrosine kinases.Science 254:1016–1019.
Ley, S. C., M. Marsh, C. R. Bebbington, K. Proudfoot, andP. Jordan. 1994. Distinct intracellular localization of Lck and Fyn protein tyrosine kinase in human T lymphocytes.J. Cell. Biol. 125:639–649.
Lancki, D. W., D. Qian, P. Fields, T. Gajewski, andF. W. Fitch. 1995. Differential requirement for protein tyrosine kinase Fyn in functional activation of antigen-specific T lymphocyte clones through the TCR or Thy-1.J. Immunol. 154:4363–4370.
Wüthrich, R. P. 1992. Monoclonal antibodies targeting murine LFA-1 induce LFA-1/ICAM-1 independent homotypic lymphocyte aggregation.Cell. Immunol. 144:22–31.
Wüthrich, R. P., L. H. Glimcher, M. A. Yui, A. M. Jevnikar, S. E. Dumas, andV. E. Kelley. 1990. MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells.Kidney Int. 37:783–792.
Rothlein, R., andT. A. Springer. 1986. The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester.J. Exp. Med. 163:1132–1149.
Wüthrich, R. P., andP. Sekar. 1993. Effect of dexamethasone, 6-mercaptopurine and cyclosporine A on ICAM-1 and VCAM-1 expression.Biochem. Pharmacol. 46:1349–1353.
Wüthrich, R. P. 1992. Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis.Kidney Int. 42:903–914.
Gunter, K. C., T. R. Malek, andE. M. Shevach. 1984. T cell-activating properties of an anti-Thy-1 monoclonal antibody.J. Exp. Med. 159:716–730.
Pont, S. A. Regnier-Vigouroux, P. Naquet, D. Blanc, A. Pierres, S. Marchetto, andM. Pierres. 1985. Analysis of the Thy-1 pathway of T cell hybridoma activation using 17 rat monoclonal antibodies reactive with distinct Thy-1 epitopes.Eur. J. Immunol. 15:1222–1228.
MacDonald, R. H., C. Bron, M. Rousseaux, C. Horvath, andJ. Cerottini. 1985. Production and characterization of monoclonal anti-Thy-1 antibodies that stimulate lymphokine production by cytolytic T cell clones.Eur. J. Immunol. 15:495–501.
Hollander, N. 1985. Antibodies to nonpolymorphic determinants of the Thy-1 molecule inhibit T cell proliferation.J. Immunol. 134:2916–2921.
Robinson, P. J. 1991. Phosphatidylinositol membrane anchors and T cell activation.Immunol. Today 12:35–41.
Nishimura, T., Y. Takeuchi, X. Gao, K. Urano, andS. Habu. 1991. Monoclonal antibody against actin cross-reacts with the Thy-1 molecule and inhibits lymphocyte function-associated antigen-1 dependent cell-cell interaction of T cells.J. Immunol. 147:2094–2099.
Hueber, A. O., G. Raposo, M. Pierres, andH. T. He. 1994. Thy-1 triggers mouse thymocyte apoptosis through a Bcl-2-resistant mechanism.J. Exp. Med. 179:785–796.
Isobe, K. I., I. Nakashima. 1991. Homotypic aggregation of murine T lymphocytes induced by anti-Thy-1 monoclonal antibodies.Immunology 73:159–164.
Garnett, D., andA. F. Williams. 1994. Homotypic adhesion of rat B cells, but not T cells, in response to cross-linking of CD48.Immunology 81:103–110.
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Fan, X., Benz, P. & Wüthrich, R.P. ICAM-1-, -2- and LFA-1-independent homotypic T cell aggregation induced by a novel activating monoclonal antibody targeting the murine Thy-1 molecule. Inflammation 20, 401–411 (1996). https://doi.org/10.1007/BF01486742
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DOI: https://doi.org/10.1007/BF01486742