Molecular mechanisms of lineage decisions in metabolite-specific T cells

François Legoux; Jules Gilet; Emanuele Procopio; Klara Echasserieau; Karine Bernardeau; Olivier Lantz

doi:10.1038/s41590-019-0465-3

Molecular mechanisms of lineage decisions in metabolite-specific T cells

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

Authors

François Legoux^#¹, Jules Gilet^#², Emanuele Procopio², Klara Echasserieau³, Karine Bernardeau³, Olivier Lantz^{4

5

6}

Affiliations

¹ INSERM U932, PSL University, Institut Curie, Paris, France. [email protected].
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. [email protected].
⁵ Laboratoire d'immunologie Clinique, Institut Curie, Paris, France. [email protected].
⁶ Centre d'investigation Clinique en Biothérapie, Gustave-Roussy Institut Curie, Paris, France. [email protected].

^# Contributed equally.

PMID: 31431722
DOI: 10.1038/s41590-019-0465-3

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Cell Differentiation / genetics
Cell Differentiation / immunology
Cell Lineage / immunology*
Histocompatibility Antigens Class I / metabolism
Hyaluronan Receptors / metabolism
Lymphocyte Activation / immunology
Mice
Mice, Knockout
Minor Histocompatibility Antigens / metabolism
Mucosal-Associated Invariant T Cells / cytology*
Mucosal-Associated Invariant T Cells / immunology*
Promyelocytic Leukemia Zinc Finger Protein / biosynthesis
Receptors, Antigen, T-Cell, alpha-beta / immunology
Ribitol / analogs & derivatives*
Ribitol / immunology
Sequence Analysis, RNA
Signaling Lymphocytic Activation Molecule Family / metabolism
Thymocytes / cytology*
Thymocytes / immunology*
Thymus Gland / cytology
Thymus Gland / immunology
Uracil / analogs & derivatives*
Uracil / immunology

Substances

5-(2-oxopropylideneamino)-6-d-ribitylaminouracil
Cd44 protein, mouse
Histocompatibility Antigens Class I
Hyaluronan Receptors
Minor Histocompatibility Antigens
Mr1 protein, mouse
Promyelocytic Leukemia Zinc Finger Protein
Receptors, Antigen, T-Cell, alpha-beta
Signaling Lymphocytic Activation Molecule Family
Slamf6 protein, mouse
Zbtb16 protein, mouse
Ribitol
Uracil