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Nat Immunol. 2019 Sep;20(9):1244-1255. doi: 10.1038/s41590-019-0465-3. Epub 2019 Aug 20.

Molecular mechanisms of lineage decisions in metabolite-specific T cells.

Author information

1
INSERM U932, PSL University, Institut Curie, Paris, France. francois.legoux@curie.fr.
2
INSERM U932, PSL University, Institut Curie, Paris, France.
3
Production de Protéines Recombinantes, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers, INSERM-1232, Nantes, France.
4
INSERM U932, PSL University, Institut Curie, Paris, France. olivier.lantz@curie.fr.
5
Laboratoire d'immunologie Clinique, Institut Curie, Paris, France. olivier.lantz@curie.fr.
6
Centre d'investigation Clinique en Biothérapie, Gustave-Roussy Institut Curie, Paris, France. olivier.lantz@curie.fr.

Abstract

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.

PMID:
31431722
DOI:
10.1038/s41590-019-0465-3
[Indexed for MEDLINE]

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