Temporally regulated amino acid uptake through SLC7A5 is required for CD4+ effector T cell differentiation

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T follicular helper cells (TFH) are critical cells for germinal center (GC) formation and for the production of high affinity, isotype-switched antibody responses. Using a novel single cell assay for System L amino acid transport, we show that the in vivo differentiation of TFH is accompanied by sustained regulation of System L amino acid transport capacity. The System L transporter, SLC7A5, has a key role in activated T cells to transport the essential amino acid methionine. Methionine is required for de novo protein synthesis and is also the biosynthetic precursor for S-adenosylmethionine (SAM), the main methyl donor used in the DNA, RNA and histone modifications that regulate cellular transcriptional programs. In particular, regulated methionine delivery to the cell interior is rate limiting for RNA methylation and for coordinating epigenetic histone modifications in immune activated T cells. SLC7A5 expression is thus a critical metabolic checkpoint linking nutrient supply to key processes required for effector T cell differentiation.
Linda was born in Lund, Sweden and had a varied international primary and secondary schooling, finally coming to rest in Scotland; she received her undergraduate degree in Immunology from Edinburgh, followed by her PhD from Dundee. Since then she has continued working with Doreen Cantrell to advance understanding on how nutrient availability impacts upon the immune system, specifically on the activation, differentiation and function of T lymphocytes. – demonstrating a novel role for the metabolic sensor mTOR in regulating lymphocyte homing (Nat Imm 2008) – demonstrating that regulated expression of SLC7A5 (an amino acid transporter) is required to co-ordinate the metabolic reprogramming of cytotoxic T cells upon antigen stimulation, both to sustain mTOR signalling and c-MYC expression (Nat Imm 2013, EMBO 2015)