Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing

Immunological synapseformation between cytotoxic T lymphocytes ( CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosometo a position beneath the synaptic membrane. Centrosomepolarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforinand granzymestoward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centrioledeletion altered microtubule architecture, as expected, but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLslacking centriolesdid display substantially reduced killing potential, which was associated with defects in both lytic granule biogenesis and synaptic actin remodeling. These results reveal an unexpected role for the intact centrosomein controlling the capacity, but not the specificity, of cytotoxic killing.