The cytotoxic T cell proteome and its shaping by mammalian Target of Rapamycin

High-resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes and mTORC1 selectively repressed and promoted expression of subset of CTL...

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Veröffentlicht in:Nature immunology 2015-11, Vol.17 (1), p.104-112
Hauptverfasser: Hukelmann, Jens L., Anderson, Karen E., Sinclair, Linda V., Grzes, Katarzyna M., Murillo, Alejandro Brenes, Hawkins, Phillip T., Stephens, Len R., Lamond, Angus I., Cantrell, Doreen A.
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Sprache:eng
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Zusammenfassung:High-resolution mass spectrometry maps the cytotoxic T lymphocyte (CTL) proteome and the impact of mammalian target of rapamycin complex 1 (mTORC1) on CTLs. The CTL proteome was dominated by metabolic regulators and granzymes and mTORC1 selectively repressed and promoted expression of subset of CTL proteins (~10%). These included key CTL effector molecules, signaling proteins and a subset of metabolic enzymes. Proteomic data highlighted the potential for mTORC1 negative control of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P 3 ) production in CTL. mTORC1 was shown to repress PtdIns(3,4,5)P 3 production and to determine the mTORC2 requirement for activation of the kinase Akt. Unbiased proteomic analysis thus provides a comprehensive understanding of CTL identity and mTORC1 control of CTL function.
ISSN:1529-2908
1529-2916
DOI:10.1038/ni.3314