Systems Model of T Cell Receptor Proximal Signaling Reveals Emergent Ultrasensitivity
Figure 6
The mathematical model predicts novel chimeric antigen receptors (CARs) design.
A) The concentration of bound ZAP-70 as a function of the relative concentration of active kinase (E) to phosphatase (F) for six cytoplasmic CAR domains. These domains include the wild-type -chain (blue), chains containing 3 copies of the low affinity ITAM from FC
RI-
(green) and FC
RI-
(red), a single high affinity
-chain ITAM (orange), and chains containing a single copy of the low affinity ITAM from FC
RI-
(magenta) and FC
RI-
(grey). B-C) Illustrates the
and
for all CARs shown in panel A. Most CARs are developed based on the wild-type
-chain but this construct, although having a large
has an undesirably large potency (low
). Novel CARs containing multiple low affinity ITAMs (e.g. (FC
RI-
)x3, (FC
RI-
)x3) have the desirably low potency (large
) while maintaining the desirably large
.