Fig. 1

Mechanisms and improvement strategies for T cell activation regulation. T cell activation is primarily controlled by three signals: MHC-antigen-peptide complex-TCR signaling, co-stimulatory signaling, and cytokine signaling. Each signal initiates signaling cascades through phosphorylation events, such as ITAM (intracellular region: yellow area) phosphorylation. T cell activation promotes differentiation and proliferation and enhances effector functions. CARs possess a structural combination of TCR and co-stimulatory molecules. Strategies considered to enhance each signal include DGK double knockout (KO) and the introduction of mbIL15