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Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses.


ABSTRACT: A longstanding paradox in the activation of cytotoxic T lymphocytes (CTL) arises from the observation that CTL recognize and rapidly destroy target cells with exquisite sensitivity despite the fact that cytokine production requires sustained signaling at the immunological synapse. Here we solve this paradox by showing that CTL establish sustained synapses with targets offering strong antigenic stimuli and that these synapses persist after target cell death. Simultaneously, CTL polarize lytic granules toward different cells without discrimination regarding antigenic potential. Our results show that spatiotemporal uncoupling of immunological synapse and lytic granule secretion allows multiple killing and sustained signaling by individual CTL. This unique mechanism of responding to multiple contacts provides remarkable efficiency to CTL function.

SUBMITTER: Wiedemann A 

PROVIDER: S-EPMC1544161 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

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Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses.

Wiedemann Aurelie A   Depoil David D   Faroudi Mustapha M   Valitutti Salvatore S  

Proceedings of the National Academy of Sciences of the United States of America 20060710 29


A longstanding paradox in the activation of cytotoxic T lymphocytes (CTL) arises from the observation that CTL recognize and rapidly destroy target cells with exquisite sensitivity despite the fact that cytokine production requires sustained signaling at the immunological synapse. Here we solve this paradox by showing that CTL establish sustained synapses with targets offering strong antigenic stimuli and that these synapses persist after target cell death. Simultaneously, CTL polarize lytic gra  ...[more]

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