Fig. 3.

The influence of binding affinity of the CAR recognition domain and the antigen load on CAR-T signal and function. a The activation threshold of CAR-T cells is mediated by their binding affinity. Within the tuning window (a < affinity < a′), the antigen load required to activate CAR-T cells is inversely related to the affinity such that the CAR-T cell can discriminate between tumor and normal cells because of their different antigen loads. The CAR-T cell will not be activated regardless of how high the antigen load is when its affinity < a, whereas the CAR-T cell will be activated by even a very low antigen load when affinity > a′. b The affinity can be tuned to selectively control CAR-T cell responses. The activation threshold of cytokine secretion is several-fold higher than that of cytolytic function; hence, the tuning windows of cytotoxicity and cytokine secretion are distinct. These discrepant windows result in a selective activation zone, colored purple, where the cytotoxic function can be activated without activating the cytokine secretion function