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Reversal of the TCR stop signal by CTLA-4

Brewer, J.M. and Schneider, Helga and Downey, Jos and Smith, Andrew and Zinselmeyer, B.H. and Rush, Catherine (2006) Reversal of the TCR stop signal by CTLA-4. Science, 313 (5795). pp. 1972-1975. ISSN 0036-8075

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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.