Journal
NATURE IMMUNOLOGY
Volume 20, Issue 9, Pages 1244-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41590-019-0465-3
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Funding
- Agence Nationale de la Recherche ('Investissements d'Avenir' program) [ANR10EQPX03, ANR10INBS0908]
- Canceropole Ile-de-France
- Marie-Sklodowska Curie individual fellowship from the European Commission [706353]
- Institut National de la Sante et de la Recherche Medicale
- Institut Curie
- Agence Nationale de la Recherche (Blanc (MAIT))
- Agence Nationale de la Recherche (Blanc (NEOMAIT))
- Agence Nationale de la Recherche (Blanc (DIABMAIT))
- Agence Nationale de la Recherche (Labex DCBIOL)
- Equipe labellisee de la Ligue Contre le Cancer
- Marie Curie Actions (MSCA) [706353] Funding Source: Marie Curie Actions (MSCA)
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Mucosal-associated invariant T cells (MAIT cells) recognize the microbial metabolite 5-(2-oxopropylideneamino)-6-D-ribity-laminouracil (5-OP-RU) presented by the MHC class lb 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 Tcells. 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.
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