(328f) Engineering Human T-Cell Receptor Signaling Dynamics

T-cells are important regulators of the immune response. Central to the immune response of T-cells is their activation through the T-cell receptor (TCR). Although under intense investigation, how the duration and level of TCR activation affects T-cell response, such as IL-2 production and T-cell proliferation, remains unclear. Recent studies have demonstrated the power of synthetic biology approaches for understanding the design principles of signaling systems; by engineering novel circuit architectures one can probe how diverse dynamic behaviors can emerge from a common set of core signaling components. Here we used the synthetic approach to create new feedback loops and TCR signaling dynamics, and ask how the different dynamics control the ultimate physiological response. By creating libraries of circuits, we can systematically map what architectures and parameters yield particular dynamic behaviors, and the physiological consequences. The discrepancy between expectations and reality will also provide us focal points to explore our knowledge gap. Moreover, this work can complement ongoing works on therapeutic T-cells engineering by creating user-defined temporal and dose-response behaviors. Furthermore, this work will yield a new set of genetic tools to control the TCR signaling dynamics that can benefit the signal transduction community.