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    Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion


    Marchingo, J.M. and Kan, A. and Sutherland, Robyn M. and Duffy, Ken R. (2014) Antigen affinity, costimulation, and cytokine inputs sum linearly to amplify T cell expansion. Science, 346 (6213). pp. 1123-1127. ISSN 0036-8075

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    Abstract

    Tcell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how Tcells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that Tcell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate,whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a Tcell response to be predicted from the sum of the underlying signal components.These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.

    Item Type: Article
    Keywords: Antigen affinity; costimulation; cytokine inputs; sum linearly; amplify T cell expansion;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Hamilton Institute
    Item ID: 8284
    Identification Number: https://doi.org/10.1126/science.1260044
    Depositing User: Dr Ken Duffy
    Date Deposited: 08 Jun 2017 13:32
    Journal or Publication Title: Science
    Publisher: American Association for the Advancement of Science
    Refereed: No
    URI:

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