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Modeling costimulation

Nature Immunology volume 1, pages 194–195 (2000)Cite this article

T cell activation usually requires TCR engagement by antigen and another, costimulatory, signal. Modeling studies now indicate that this second signal may only slightly enhance TCR signaling, but nevertheless results in an exponential increase in cell numbers.

The two-signal or costimulation model of T cell activation was first proposed by Lafferty and colleagues1,2 to explain why transplants of foreign tissue are not always rejected. They postulated that full activation of naïve T cells requires engagement of an antigen receptor by foreign antigen (signal one) as well as engagement of a “costimulatory” receptor by a soluble or cell surface ligand provided by the antigen presenting cell (signal two). This two-signal model is consistent with a considerable body of experimental data and is now widely accepted. Variants of the model, for which the evidence is less compelling, propose that delivery of signal one alone inactivates T cells by killing them3 or rendering them unresponsive (anergic)4. In this issue of Nature Immunology Gett and Hodgkin investigate costimulation using modeling5.

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Figure 1: (a) An updated two-signal model of T cell activation.

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  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    P. Anton van der Merwe

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  1. P. Anton van der Merwe
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van der Merwe, P. Modeling costimulation. Nat Immunol 1, 194–195 (2000). https://doi.org/10.1038/79729

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