Role of accessory molecules in signal transduction of cytolytic T lymphocyte by anti-T cell receptor and anti-Ly-6.2C monoclonal antibodies.
Accessory molecules present on the cell surface of cytolytic T lymphocytes (CTL) play an important role in their activation. Antigen-specific recognition by CTL is inhibited by antibodies against Lyt-2, L3T4, or LFA-1 molecules. Presently it is not known whether these molecules function by binding a ligand such as class I or class II on the target cell or by delivering a signal that down-regulates T cell activation. In the present study we utilized anti-T cell antibodies including anti-T3 and anti-T cell receptor (alpha/beta) as well as an anti-Ly-6.2C monoclonal antibody to activate CTL clones to kill irrelevant targets or secrete BLT esterase. The redirected lysis assay system utilizes the fact that heteroconjugates between anti-T3, and anti-T cell receptor, or anti-Ly-6.2C and anti-trinitrophenyl can trigger CTL lysis of trinitrophenyl-coupled targets that did not express antigen. In this system anti-Lyt-2 antibodies as well as anti-LFA-1 antibodies inhibited triggering via T cell receptor-related molecules but not via the anti-Ly-6.2C heteroconjugate. In addition, the anti-Lyt-2 was shown to inhibit conjugate formation in the heteroaggregate assay system suggesting that the anti-Lyt-2 antibodies acted early in inhibiting CTL activity. Similar results were observed in a system in which the CTL clones were triggered to secrete a BLT-esterase-like activity in the absence of target cells. Anti-T3 coated on plastic was shown to activate BLT-esterase secretion. This secretion was inhibited by anti-Lyt-2 and anti-LFA-1. Thus, it would appear that both the Lyt-2 molecule and the LFA-1 molecule act as signal-transducing elements involved in CTL activation. In particular, the Lyt-2 molecule appears to preferentially function in receptor-mediated T cell activation.
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Transplantation Biology Section, National Cancer Institute, Bethesda, MD 20892.
Foo
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Henkart
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Perez
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Shinohara
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Segal
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Bluestone
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000950:Antigens, Ly / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004950:Esterases / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D006649:Histocompatibility Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D004950:Esterases; C022635:serine esterase