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

doi:10.1126/science.1131078

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 journal › Article › peer-review

516 Scopus citations

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.

Original language	English
Pages (from-to)	1972-1975
Number of pages	4
Journal	Science
Volume	313
Issue number	5795
DOIs	https://doi.org/10.1126/science.1131078
State	Published - Sep 29 2006

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title = "Reversal of the TCR stop signal by CTLA-4",

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.",

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

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AU - Schneider, Helga

AU - Downey, Jos

AU - Smith, Andrew

AU - Zinselmeyer, Bernd H.

AU - Rush, Catherine

AU - Brewer, James M.

AU - Wei, Bin

AU - Hogg, Nancy

AU - Garside, Paul

AU - Rudd, Christopher E.

PY - 2006/9/29

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N2 - 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.

AB - 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.

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SN - 0036-8075

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Reversal of the TCR stop signal by CTLA-4

Abstract

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