CTX-B INHIBITS CTL CYTOTOXICITY AND CYTOSKELETAL MOVEMENTS

Binding of cytotoxic T lymphocytes (CTL) to specific targets induces c ytoskeletal movements in the effector cell followed by delivery of the lethal hit which ultimately results in target cell lysis. The questio n whether movement of the cytoskeleton in CTL are obligatory for deliv ery of the lethal hit is not resolved. Here we report that the CTX-B s ubunit of cholera toxin which is devoid of the catalytic CTX-A subunit inhibits CTL function. Inhibition was found not to be due to interfer ence with TCR expression, CTL-target conjugate formation, target induc ed transmembrane signalling or secretion of BLT-esterase. CTX-B howeve r does interfere with F-actin patch formation at the effector target b inding site and inhibits reorientation of the microtubule organizing c enter and Golgi apparatus towards the target binding site. It is concl uded that interference with cytoskeletal movements is responsible for inhibition of cytolysis pointing to an important role of the cytoskele ton in the lytic reaction.