Molecular mechanisms of lineage decisions in metabolite-specific T cells.
Francois LegouxJules GiletEmanuele ProcopioKlara EchasserieauKarine BernardeauOlivier LantzPublished in: Nature immunology (2019)
Mucosal-associated invariant T cells (MAIT cells) recognize the microbial metabolite 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) presented by the MHC class Ib molecule, MR1. MAIT cells acquire effector functions during thymic development, but the mechanisms involved are unclear. Here we used single-cell RNA-sequencing to characterize the developmental path of 5-OP-RU-specific thymocytes. In addition to the known MAIT1 and MAIT17 effector subsets selected on bone-marrow-derived hematopoietic cells, we identified 5-OP-RU-specific thymocytes that were selected on thymic epithelial cells and differentiated into CD44- naive T cells. MAIT cell positive selection required signaling through the adapter, SAP, that controlled the expression of the transcription factor, ZBTB16. Pseudotemporal ordering of single cells revealed transcriptional trajectories of 5-OP-RU-specific thymocytes selected on either thymic epithelial cells or hematopoietic cells. The resulting model illustrates T cell lineage decisions.
Keyphrases
- single cell
- induced apoptosis
- cell cycle arrest
- transcription factor
- rna seq
- endoplasmic reticulum stress
- magnetic resonance imaging
- gene expression
- oxidative stress
- cell death
- mesenchymal stem cells
- computed tomography
- stem cells
- magnetic resonance
- regulatory t cells
- hiv infected
- bone marrow
- poor prognosis
- binding protein