title: Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids.
abstract: 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 G1phase 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 G1phase 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.
authors: From the Departments of Infectious Diseases and.|Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors: Lee-Ann
authors: LA
authors: Van de Velde
authors: From the Departments of Infectious Diseases and peter.murray@stjude.org.|Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors: Peter J
authors: PJ
authors: Murray
mesh_terms: D000596:Amino Acids / Q000276:immunology; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D060833:Cellular Microenvironment / Q000235:genetics / Q000276:immunology*; D016193:G1 Phase / Q000235:genetics / Q000276:immunology*; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D008807:Mice, Inbred BALB C; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D046912:Multiprotein Complexes; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; C525637:rictor protein, mouse; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases
keywords: T helper cells; amino acid; immunology; immunosuppression; mTOR complex (mTORC)