Systems Model of T Cell Receptor Proximal Signaling Reveals Emergent Ultrasensitivity
Figure 2
Multiple -chain ITAMs not only mediate signal amplification, but also increase potency and sensitivity.
A) The concentration of ITAM-bound ZAP-70 as a function of the relative kinase (E) to phosphatase (F) concentration. As expected, when the phosphatase is in excess the -chain is dephosphorylated and ZAP-70 cannot bind whereas when the kinase is in excess the
-chain is phosphorylated and ZAP-70 is fully bound. Results are shown for the wild-type
-chain (
123) and for
-chains where the first and second ITAMs are removed,
X23 and
XX3, respectively. Inset shows normalized curves, highlighting differences in potency (
) and sensitivity (Hill number), which is a measure of the curve steepness. Each curve is fit to a Hill function to extract estimates of B) the maximum (
), C) the potency (
), and D) the sensitivity (Hill number). Model and parameter values can be found in Methods.