Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation

Sinclair LV, Cantrell DA et al. · 2013 · Nature immunology · Atlas ID SIN2013

What this study shows

Antigen-receptor-driven System-L (SLC7A5) amino-acid transport controls mTORC1 and T-cell differentiation.

Abstract

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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.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse T cells); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse T cells
Journal	Nature immunology
Year	2013
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1038/ni.2556 · PMID 23525088 · Free full text (PMC3672957)

Extracted findings

Intervention	Genetic (Slc7a5, T-cell receptor)
Target	Slc7a5 (System L) / leucine / mTORC1
Model	Mouse T cells
Effect	Antigen-receptor-driven Slc7a5 amino-acid transport coordinates the metabolic reprogramming essential for T-cell differentiation
Dose	TCR triggering with cognate peptide for 4h or 20h; IL-2 at 20 ng/ml or 1.25 ng/ml for 20h; BCH at 10 mM or 50 mM; rapamycin at 20 nM; CsA at 100 nM; glutamine at 2 mM; leucine at 0.4 mM.
Sample size	minimum of 3 experiments done in triplicates (Fig. 1a,c,d); 6 mice (Fig. 1b); 3 experiments (Fig. 2); 3 mice per group (Fig. 3a); 2 collated experiments (Fig. 3d-f).
Effect size	TCR triggering increased phenylalanine transport (p=0.0147 at 4h, p<0.0001 at 20h); CsA abrogated TCR-induced system L activity (p=0.0242) and Slc7a5 mRNA expression (p=0.0070); Slc7a5 haplo-insufficient T cells showed a 50% reduction in System L transporter activity.
Limitations	Systemic deletion of Slc7a5 causes embryonic lethality, necessitating the use of haplo-insufficient mice.

Cite this paper

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Sinclair, L. V., et al. (2013). Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation. Nature immunology. https://doi.org/10.1038/ni.2556

@article{SIN2013,
  author       = {Sinclair, L. V. and Cantrell, D. A. and others},
  title        = {{Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation}},
  journal      = {Nature immunology},
  year         = {2013},
  doi          = {10.1038/ni.2556},
  note         = {PMID: 23525088},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record SIN2013) [Data set]. https://mtor-atlas.org/study/SIN2013/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SIN2013,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SIN2013},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SIN2013/},
  doi          = {10.5281/zenodo.22059963}
}