Title | T Cell Activation Depends on Extracellular Alanine. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Ron-Harel, N, Ghergurovich, JM, Notarangelo, G, LaFleur, MW, Tsubosaka, Y, Sharpe, AH, Rabinowitz, JD, Haigis, MC |
Journal | Cell Rep |
Volume | 28 |
Issue | 12 |
Pagination | 3011-3021.e4 |
Date Published | 2019 Sep 17 |
ISSN | 2211-1247 |
Keywords | Alanine, Animals, Immunologic Memory, Lymphocyte Activation, Mice, T-Lymphocytes |
Abstract | <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> |
DOI | 10.1016/j.celrep.2019.08.034 |
Alternate Journal | Cell Rep |
PubMed ID | 31533027 |
PubMed Central ID | PMC6934407 |
Grant List | R01 CA213062 / CA / NCI NIH HHS / United States U54 CA225088 / CA / NCI NIH HHS / United States |