Figure 3 Defects in the T cell receptor signalling pathway Figure 3 | Defects in the T cell receptor signalling pathway. Constitutive activation of phosphatidylinositol 4,5-bisphosphate 3-kinase δ (PI3Kδ) by gain-of-function mutations leads to an increase in RACα serine/threonine-protein kinase (AKT) phosphorylation and ribosomal protein S6 kinase β1 (S6K1) signalling. Loss of the PI3K inhibitor PTEN likewise leads to increased PI3Kδ activity, causing lymphoproliferation, autoimmunity and antibody deficiency. mTOR, mechanistic target of rapamycin; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; TCR, T cell receptor. Schmidt, R. E. et al. (2017) Autoimmunity and primary immunodeficiency: two sides of the same coin? Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2017.198