Balancing speed and accuracy of polyclonal T cell activation: a role for extracellular feedback

Yonatan Savir, Nir Waysbort, Yaron E. Antebi, Tsvi Tlusty, Nir Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: Extracellular feedback is an abundant module of intercellular communication networks, yet a detailed understanding of its role is still lacking. Here, we study interactions between polyclonal activated T cells that are mediated by IL-2 extracellular feedback as a model system.Results: Using mathematical modeling we show that extracellular feedback can give rise to opposite outcomes: competition or cooperation between interacting T cells, depending on their relative levels of activation. Furthermore, the outcome of the interaction also depends on the relative timing of activation of the cells. A critical time window exists after which a cell that has been more strongly activated nevertheless cannot exclude an inferior competitor.Conclusions: In a number of experimental studies of polyclonal T-cell systems, outcomes ranging from cooperation to competition as well as time dependent competition were observed. Our model suggests that extracellular feedback can contribute to these observed behaviors as it translates quantitative differences in T cells' activation strength and in their relative activation time into qualitatively different outcomes. We propose extracellular feedback as a general mechanism that can balance speed and accuracy - choosing the most suitable responders out of a polyclonal population under the clock of an escalating threat.

Original languageAmerican English
Article number111
JournalBMC Systems Biology
StatePublished - 27 Aug 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank Uri Alon, Benjamin Chain, Ofer Feinerman, Ron Milo, Wilfred Ndifon and Jacob Rimer for helpful comments on the manuscript. This research was supported by The International Human Frontier Science Program Organization and by the Abisch-Frenkel Foundation. TT thanks the Simons Foundation, and Helen and Martin Chooljian for their generous support. TT is the Helen and Martin Chooljian Founders' Circle Member in the Simons Center for Systems Biology at the Institute for Advanced Studies, Princeton. NF is incumbent of the Pauline Recanati Career Development Chair of Immunology.


  • CD25
  • IL-2
  • Positive feedback
  • Speed vs. accuracy
  • Systems immunology


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