Reversal of the TCR stop signal by CTLA-4

Journal Publication ResearchOnline@JCU
Schneider, Helga;Downey, Jos;Smith, Andrew;Zinselmeyer, Bemd H.;Rush, Catherine;Brewer, James M.;Wei, Bin;Hogg, Nancy;Garside, Paul;Rudd, Christopher E.
Catherine Rush
Abstract

The coreceptor cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is pivotal in regulating the threshold of signals during T cell activation, although the underlying mechanism is still not fully understood. Using in vitro migration assays and in vivo two-photon laser scanning microscopy, we showed that CTLA-4 increases T cell motility and overrides the T cell receptor (TCR)-induced stop signal required for stable conjugate formation between T cells and antigen-presenting cells. This event led to reduced contact periods between T cells and antigen-presenting cells that in turn decreased cytokine production and proliferation. These results suggest a fundamentally different model of reverse stop signaling, by which CTLA-4 modulates the threshold for T cell activation and protects against autoimmunity.

Journal

Science

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Volume

313

ISBN/ISSN

1095-9203

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Issue

5795

Pages Count

4

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Publisher

American Association for the Advancement of Science

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EISSN

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DOI

10.1126/science.1131078