Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation.

Autor:	Karnaukhov VK; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France.; Laboratoire de Physique de l'École Normale Supérieure, Paris Sciences & Lettres University, CNRS, Sorbonne Université and Université Paris Cité, Paris 75005, France., Le Gac AL; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France., Bilonda Mutala L; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France., Darbois A; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France., Perrin L; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France., Legoux F; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France.; INSERM Equipe de Recherche Labellisée 1305, CNRS UMR6290, Université de Rennes, Institut de Génétique & Développement de Rennes 35000, France., Walczak AM; Laboratoire de Physique de l'École Normale Supérieure, Paris Sciences & Lettres University, CNRS, Sorbonne Université and Université Paris Cité, Paris 75005, France., Mora T; Laboratoire de Physique de l'École Normale Supérieure, Paris Sciences & Lettres University, CNRS, Sorbonne Université and Université Paris Cité, Paris 75005, France., Lantz O; Institut Curie, Paris Sciences & Lettres University, Inserm U932, Immunity and Cancer, Paris 75005, France.; Laboratoire d'Immunologie Clinique, Département de médecine diagnostique et théranostique, Institut Curie, Paris 75005, France.; Centre d'Investigation Clinique en Biothérapie Gustave-Roussy Institut Curie (CIC-BT1428), Paris 75005, France.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Apr 02; Vol. 121 (14), pp. e2311348121. Date of Electronic Publication: 2024 Mar 26.
DOI:	10.1073/pnas.2311348121
Abstrakt:	How T-cell receptor (TCR) characteristics determine subset commitment during T-cell development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. MAIT and iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) and IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role for TCR affinity was proposed but recent data argue against this model. Herein, we examined TCR role in MAIT and iNKT subset commitment through scRNAseq and TCR repertoire analysis. In our dataset of thymic MAIT cells, we found pairs of T-cell clones with identical amino acid TCR sequences originating from distinct precursors, one of which committed to MAIT1 and the other to MAIT17 fates. Quantitative in silico simulations indicated that the number of such cases is best explained by lineage choice being independent of TCR characteristics. Comparison of TCR features of MAIT1 and MAIT17 clonotypes demonstrated that the subsets cannot be distinguished based on TCR sequence. To pinpoint the developmental stage associated with MAIT sublineage choice, we demonstrated that proliferation takes place both before and after MAIT fate commitment. Altogether, we propose a model of MAIT cell development in which noncommitted, intermediate-stage MAIT cells undergo a first round of proliferation, followed by TCR characteristics-independent commitment to MAIT1 or MAIT17 lineage, followed by an additional round of proliferation. Reanalyzing a published iNKT TCR dataset, we showed that this model is also relevant for iNKT cell development. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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