Reversal of the TCR stop signal by CTLA-4

Helga Schneider, Jos Downey, Andrew Smith, Bernd H. Zinselmeyer, Catherine Rush, James M. Brewer, Bin Wei, Nancy Hogg, Paul Garside, Christopher E. Rudd

Research output: Contribution to journalArticlepeer-review

463 Scopus citations


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.

Original languageEnglish
Pages (from-to)1972-1975
Number of pages4
Issue number5795
StatePublished - Sep 29 2006


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