Distinct sensing of BCAAs by mTOR and c-Myc governs T cell proliferation, independent of catabolism.

Isoleucine and valine, but not leucine, are necessary and sufficient for quiescence exit and T cell division, driven by distinct mTOR and c-Myc sensing rather than catabolism.

• Why it matters: BCAAs signal through mTORC1 and can be catabolized, but how each BCAA specifically controls T cell proliferation is unclear, limiting mechanistic understanding of immune regulation.
• What they did: The study tested BCAA requirements for quiescence exit and cell division and assessed whether effects depended on catabolic fates; it then linked isoleucine/valine to c-Myc expression and leucine to mTORC1 sensing.
• The result: Isoleucine and valine are necessary and sufficient for c-Myc expression, while mTORC1 leucine-sensing represses c-Myc and proliferation during BCAA restriction, uncoupling mTORC1 and c-Myc in T cell growth.

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