Research ArticleImmunology

Cell-to-Cell Variability Analysis Dissects the Plasticity of Signaling of Common γ Chain Cytokines in T Cells

Sci. Signal.  12 Mar 2013:
Vol. 6, Issue 266, pp. ra17
DOI: 10.1126/scisignal.2003240

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Signaling Denied by Sequestration

The γc family of cytokines, including interleukin-2 (IL-2) and IL-7, bind to receptors containing different α subunits but the same common γ chain. Cotari et al. used flow cytometry to simultaneously measure γc cytokine receptor abundance and downstream signaling responses of individual mouse T cells. Whereas cells with increased abundance of the α subunit of the IL-2 receptor α (IL-2Rα) had an expected correlation with increased sensitivity to IL-2, they also exhibited an unexpected decrease in responsiveness to IL-7. Mathematical modeling predicted that increased IL-2Rα abundance would sequester the γc chain from the IL-7Rα subunit, which would decrease the sensitivity of the T cells to IL-7. Further experiments validated this prediction. Changes in IL-2Rα abundance did not affect the signaling of other γc family cytokines, which could be attributed to higher affinities between their receptor α subunits and the γc chain.