PYGBacking on glycogen metabolism to fuel early memory T cell recall responses

Abstract

Zhang et al. (2022) show that TCR signaling promotes the phosphorylation and activation of glycogen phosphorylase B (PYGB) in CD8⁺ memory T (Tmem) cells. PYGB-dependent glycogen mobilization provides a carbon source to support glycolysis and early Tmem cell recall responses.

Figure 1.. Glycogen mobilization fuels the early recall response in CD8⁺ Tmem cells

Upon re-infection, antigenic stimulation of the TCR on CD8⁺ Tmem cells leads to LCK/ZAP70-mediated tyrosine phosphorylation and activation of PYGB, which promotes glycogen mobilization. During the early recall response (0–8 h post-stimulation), glycogen-derived G6P primarily fuels glycolysis but also enters the pentose phosphate pathway (PPP) to support NADPH production. Expression of the glucose transporter GLUT1 increases 8–12 h post-stimulation, resulting in glucose uptake. During the late recall response (12–24 h post-stimulation), exogenous glucose takes over as the primary fuel of glycolysis, while glycogenolysis continues to support the PPP. This metabolic reprogramming enables a rapid glycolytic switch to satisfy the initial energy and redox demands of Tmem cells as they become activated and acquire effector function (i.e., secrete cytokines such as TNF-α and IFN-γ).