Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids

Antigen-stimulated T cells require elevated importation of essential and non-essential amino acids to generate large numbers of daughter cells necessary for effective immunity to pathogens. When amino acids are limiting, T cells arrest in the G(1) phase of the cell cycle, suggesting that they have specific sensing mechanisms to ensure sufficient amino acids are available for multiple rounds of daughter generation. We found that activation of mTORC1, which is regulated by amino acid amounts, was uncoupled from limiting amino acids in the G(1) phase of the cell cycle. Instead, we found that Rictor/mTORC2 has an essential role in T cell amino acid sensing. In the absence of Rictor, CD4(+) T cells proliferate normally in limiting arginine or leucine. Our data suggest that Rictor/mTORC2 controls an amino acid-sensitive checkpoint that allows T cells to determine whether the microenvironment contains sufficient resources for daughter cell generation.