Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 500-508 |
| Number of pages | 9 |
| Journal | Nature Immunology |
| Volume | 14 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2013 |
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Keywords
- LYMPHOCYTE ACTIVATION
- GENERATION
- GENE-EXPRESSION
- MEMORY
- MTOR
- MAMMALIAN TARGET
- KINASE
- IN-VIVO
- TRANSFER-RNA SYNTHETASE
- 4F2 HEAVY-CHAIN
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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. / Sinclair, Linda V; Rolf, Julia; Emslie, Elizabeth; Shi, Yun-Bo; Taylor, Peter M; Cantrell, Doreen A (Lead / Corresponding author).
In: Nature Immunology, Vol. 14, No. 5, 05.2013, p. 500-508.Research output: Contribution to journal › Article
TY - JOUR
T1 - Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation
AU - Sinclair, Linda V
AU - Rolf, Julia
AU - Emslie, Elizabeth
AU - Shi, Yun-Bo
AU - Taylor, Peter M
AU - Cantrell, Doreen A
PY - 2013/5
Y1 - 2013/5
N2 - T lymphocytes must regulate nutrient uptake to meet the metabolic demands of an immune response. Here we show that the intracellular supply of large neutral amino acids (LNAAs) in T cells was regulated by pathogens and the T cell antigen receptor (TCR). T cells responded to antigen by upregulating expression of many amino-acid transporters, but a single System L ('leucine-preferring system') transporter, Slc7a5, mediated uptake of LNAAs in activated T cells. Slc7a5-null T cells were unable to metabolically reprogram in response to antigen and did not undergo clonal expansion or effector differentiation. The metabolic catastrophe caused by loss of Slc7a5 reflected the requirement for sustained uptake of the LNAA leucine for activation of the serine-threonine kinase complex mTORC1 and for expression of the transcription factor c-Myc. Control of expression of the System L transporter by pathogens is thus a critical metabolic checkpoint for T cells.
AB - T lymphocytes must regulate nutrient uptake to meet the metabolic demands of an immune response. Here we show that the intracellular supply of large neutral amino acids (LNAAs) in T cells was regulated by pathogens and the T cell antigen receptor (TCR). T cells responded to antigen by upregulating expression of many amino-acid transporters, but a single System L ('leucine-preferring system') transporter, Slc7a5, mediated uptake of LNAAs in activated T cells. Slc7a5-null T cells were unable to metabolically reprogram in response to antigen and did not undergo clonal expansion or effector differentiation. The metabolic catastrophe caused by loss of Slc7a5 reflected the requirement for sustained uptake of the LNAA leucine for activation of the serine-threonine kinase complex mTORC1 and for expression of the transcription factor c-Myc. Control of expression of the System L transporter by pathogens is thus a critical metabolic checkpoint for T cells.
KW - LYMPHOCYTE ACTIVATION
KW - GENERATION
KW - GENE-EXPRESSION
KW - MEMORY
KW - MTOR
KW - MAMMALIAN TARGET
KW - KINASE
KW - IN-VIVO
KW - TRANSFER-RNA SYNTHETASE
KW - 4F2 HEAVY-CHAIN
U2 - 10.1038/ni.2556
DO - 10.1038/ni.2556
M3 - Article
C2 - 23525088
VL - 14
SP - 500
EP - 508
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 5
ER -