T-cell-receptor-independent activation of cytolytic activity of cytotoxic T lymphocytes mediated through CD44 and gp90MEL-14.
CD44 is a transmembrane glycoprotein found on a variety of cells including those of myeloid and lymphoid origin. CD44 is highly conserved among various species and is involved in the homing of lymphocytes and monocytes to lymph nodes, Peyer's patches, and sites of inflammation. In the present study, we demonstrate that monoclonal antibody (mAb) 9F3, directed against murine phagocytic glycoprotein 1 (CD44) expressed on cytotoxic T lymphocytes (CTLs), can trigger the lytic activity of CTLs and redirect CTL-mediated lysis to antigen-negative Fc receptor-positive target cells. Similar redirected lysis was also inducible using mAb MEL-14, directed against the lymphocyte homing receptor for endothelium (gp90MEL-14). The redirected lysis induced by mAbs 9F3 and MEL-14 was similar to that induced by mAbs against the alpha beta T-cell receptor or CD3. In contrast, mAbs directed against CD8, CD45R, and CD11a (LFA-1, lymphocyte function-associated antigen 1) failed to evoke lytic activity. The current study demonstrates that CD44 and gp90MEL-14 molecules, in addition to participating in T-cell homing and adhesion, may play a major role in delivering the transmembrane signal to the CTL that triggers the lytic activity, even when the T-cell receptor is not occupied. Such a mechanism may account for the nonspecific tissue damage seen at sites of CTL-mediated inflammation.
Seth
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Department of Biology, Virginia Polytechnic Institute and State University, Blacksburg 24061.
Gote
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Nagarkatti
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Nagarkatti
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D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D007700:Kinetics; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing