Fig. 7 |. PIP₂ saturation defines early activation versus late effector T cell signaling.

Early CD8⁺ T cell activation is marked by a robust phosphorylation of PLCγ1, which cleaves polyunsaturated PIP₂ to generate the second messengers DAG and IP₃. In fully differentiated CD8⁺ T_eff cells, PLCγ1 phosphorylation decreases as TCR signals dissipate; and a lipid raft-accumulated saturated PIP₂ pool, synthesized de novo from glucose, becomes essential for sustained signaling and T_eff cell survival, proliferation and cytokine production. When de novo PI synthesis is inhibited, the saturated PIP₂ pool is specifically depleted, and this results in disturbed downstream signaling and reduced T_eff cell fitness and function. Glc, glucose; MAPK, mitogen-activated protein kinase; T_eff, CD8⁺ T_eff cell. Created with BioRender.com.