TCR signaling-triggered glycogenolysis fuels early recall response of CD8+ memory T cells

Glycolytic metabolism mediates the rapid recall response of CD8+ memory T (Tm) cells. Whether the Tm cells use exogenous glucose or mobilize endogenous sugar to feed the glycolysis remains unclear. Here, we show that intracellular glycogen rather than exogenous glucose acts as the carbon source that mediates the rapid early recall response. We find that CD8+ Tm cells exhibit high glycogen phosphorylase (brain form, PYGB) activity following antigenic stimulation, leading to the formation of glucose-6-phosphate (G6P) via glycogenolysis. The G6P mainly flows to glycolysis but is partially channeled to the pentose phosphate pathway required for the rapid and high-quality recall responses, respectively. Mechanistically, the phosphorylation and activation of PYGB are mediated by the binding of TCR signaling molecules LCK-ZAP70. We demonstrate that this glycogenolysis-fueled early recall response of CD8+ Tm cells is also present in the OVA-Listeria monocytogenes infection mouse model. Thus, glycogenolysis-provided carbon fuels the immediate-early recall response of CD8+ Tm cells.