PT  - JOURNAL ARTICLE
AU  - Fella Tamzalit
AU  - Diana Tran
AU  - Weiyang Jin
AU  - Vitaly Boyko
AU  - Hisham Bazzi
AU  - Ariella Kepecs
AU  - Lance C. Kam
AU  - Kathryn V. Anderson
AU  - Morgan Huse
TI  - Centrioles control the capacity, but not the specificity, of cytotoxic T cell killing
AID  - 10.1101/710053
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 710053
4099  - http://biorxiv.org/content/early/2019/07/22/710053.short
4100  - http://biorxiv.org/content/early/2019/07/22/710053.full
AB  - Immunological synapse formation between cytotoxic T lymphocytes (CTLs) and the target cells they aim to destroy is accompanied by reorientation of the CTL centrosome to a position beneath the synaptic membrane. Centrosome polarization is thought to enhance the potency and specificity of killing by driving lytic granule fusion at the synapse and thereby the release of perforin and granzymes toward the target cell. To test this model, we employed a genetic strategy to delete centrioles, the core structural components of the centrosome. Centriole deletion altered microtubule architecture, as expected, but surprisingly had no effect on lytic granule polarization and directional secretion. Nevertheless, CTLs lacking centrioles did 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 centrosome in controlling the capacity, but not the specificity, of cytotoxic killing.