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The kinetic-segregation model: TCR triggering and beyond

Nature Immunology volume 7, pages 803–809 (2006)Cite this article

Abstract

How the T cell receptor engages antigen is known, but not how that 'triggers' intracellular signaling. The first direct support for a mechanism based on the spatial reorganization of signaling proteins, proposed 10 years ago and referred to as the 'kinetic-segregation' model, is now beginning to emerge, along with indications that it may also apply to the triggering of nonclonotypic receptors. We describe here the development of the model, review new data and suggest how the model fits a broader conceptual framework for receptor triggering. We also consider the capacity of the model, versus that of other proposals, to account for the established features of TCR triggering.

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Figure 1: The KS model.
Figure 2: Evidence supporting the KS model.
Figure 3: Broad implications of the KS model.

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Acknowledgements

We thank our colleagues for discussions and criticism. Supported by The Wellcome Trust and the United Kingdom Medical Research Council.

Author information

Authors and Affiliations

  1. Nuffield Department of Clinical Medicine, The University of Oxford, and MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, OX3 9DS, Oxford, UK

    Simon J Davis

  2. Sir William Dunn School of Pathology, The University of Oxford, Oxford, OX1 3RE, UK

    P Anton van der Merwe

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Supplementary information

Supplementary Video 1

An annotated FLASH animation illustrating the KS model (this can also be seen at www.t-cellbiology.org/ks_model). (MOV 4049 kb)

Supplementary Video 2

An annotated FLASH animation showing how the model can be extended to explain signaling by conventional and superagonistic antibodies (this can also be seen at www.t-cellbiology.org/antibody). (MOV 1538 kb)

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Davis, S., van der Merwe, P. The kinetic-segregation model: TCR triggering and beyond. Nat Immunol 7, 803–809 (2006). https://doi.org/10.1038/ni1369

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