Figure 2.

Mechanism of T cell activation through TCR signaling. The TCR complex recognizes antigenic peptides presented by MHC I molecules on APCs. CD8 co-receptor binds to MHC I, stabilizing the interaction. Upon antigen recognition, the ITAMs on CD3 are phosphorylated by the associated kinase LCK, leading to the recruitment and activation of ZAP70. This initiates downstream signaling cascades involving pathways such as PI3K-AKT-mTOR, NFAT, NF-κB, and MAPK, which ultimately result in T cell activation, proliferation, and effector functions. Co-stimulatory signals, provided by CD28 binding to CD86 and 4-1BBL binding to 4-1BB, are crucial for full T cell activation. These signals enhance the activation of downstream signaling pathways, promoting T cell survival, proliferation, and cytokine production. In contrast, co-inhibitory signals, mediated by CTLA-4 and PD-1 interacting with CD80 and PD-L1, respectively, dampen T cell activation. These inhibitory signals play a critical role in maintaining immune homeostasis and preventing overactivation, but in the context of cancer, they can contribute to immune evasion by tumors. Balancing co-stimulatory and co-inhibitory signals is essential for regulating T cell responses in both immunity and immunotherapy. The images in the figures were created using BioRender (https://www.biorender.com/).