T Cell Activation Depends on Extracellular Alanine.

TitleT Cell Activation Depends on Extracellular Alanine.
Publication TypeJournal Article
Year of Publication2019
AuthorsRon-Harel, N, Ghergurovich, JM, Notarangelo, G, LaFleur, MW, Tsubosaka, Y, Sharpe, AH, Rabinowitz, JD, Haigis, MC
JournalCell Rep
Date Published2019 09 17
KeywordsAlanine, Animals, Immunologic Memory, Lymphocyte Activation, Mice, T-Lymphocytes

<p>T cell stimulation is metabolically demanding. To exit quiescence, T cells rely on environmental nutrients, including glucose and the amino acids glutamine, leucine, serine, and arginine. The expression of transporters for these nutrients is tightly regulated and required for T cell activation. In contrast to these amino acids, which are essential or require multi-step biosynthesis, alanine can be made from pyruvate by a single transamination. Here, we show that extracellular alanine is nevertheless required for efficient exit from quiescence during naive T cell activation and memory T cell restimulation. Alanine deprivation leads to metabolic and functional impairments. Mechanistically, this vulnerability reflects the low expression of alanine aminotransferase, the enzyme required for interconverting pyruvate and alanine, whereas activated T cells instead induce alanine transporters. Stable isotope tracing reveals that alanine is not catabolized but instead supports protein synthesis. Thus, T cells depend on exogenous alanine for protein synthesis and normal activation.</p>

Alternate JournalCell Rep
PubMed ID31533027
PubMed Central IDPMC6934407
Grant ListR01 CA213062 / CA / NCI NIH HHS / United States
U54 CA225088 / CA / NCI NIH HHS / United States