Skip to main content
. 2020 Jun 9;9(6):1427. doi: 10.3390/cells9061427

Figure 3.

Figure 3

A simplified overview of the CD28, PD-1, and TCR signaling pathways in T cells. Upon the binding of PD-1 with its specific ligand, SHP2 is recruited to specific sites of the ITSM motif of PD-1’s cytoplasmic tail. SHP2 dephosphorylates CD28, thus preventing recruitment of PI3K and activation of the AKT signaling pathway, leading to a reduction in T cell proliferation and activation. In the presence of anti-PD-1 MoAbs, SHP2 is sequestered by PD-1, thus allowing CD28 phosphorylation and recruitment of PI3K, which leads to GSK-3β inhibition via AKT signaling. Inhibition of GSK-3β promotes the transcription of Lag3 (LAG-3) and Tbx21 (T-bet). T-bet expression inhibits transcription of Pdcd1 (PD-1). TCR-specific stimulation leads to the inactivation of GSK-3β.