Conversion of the non-essential amino acid serine into glycine as part of one-carbon metabolism is a key metabolic node in proliferating cells. Serine can be synthesized from glucose or can be taken up from exogenous sources. In Cell Metabolism, Jones and colleagues report that extracellular serine is critical for the proliferation of T cells after antigen stimulation. Genes encoding products involved in serine biosynthesis are upregulated in activated CD8+ T cells in humans and mice, but 75% of the serine pool is derived from extracellular sources. Mice on a serine- and glycine-restricted diet show less population expansion of antigen-specific CD8+ and CD4+ T cells and diminished secondary responses, while T cells cultured in serine-free medium show less proliferation but normal expression of activation markers, cytokine secretion and glucose bioenergetics. The conversion of extracellular serine to glycine is essential for nucleotide synthesis in proliferating T cells.

Cell Metab. 25, 345–357 (2017)