Figure 3: Costimulation signaling. Additional engagement of cell surface receptors such as CD28 provides and integrates signals required for anergy avoidance and productive T cell activation. The signaling generated by CD28 ligation has no unique effects but enhances the T cell signaling, including pathways of PI3K–Akt–mTOR, NF-κB, NFAT-AP1, and MAPK.