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Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

ABSTRACT: Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-? chain and restricting molecule MR1, this population is rare in laboratory mouse strains (?0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J mice. Increased MAIT frequency was linked to one CAST genetic trait that mapped to the TCR-? locus and led to higher usage of the distal V? segments, including V?19. We generated a MAIThi congenic strain that was then crossed to a transgenic Rorcgt-GFP reporter strain. Using this tool, we characterized polyclonal mouse MAITs as memory (CD44+) CD4-CD8lo/neg T cells with tissue-homing properties (CCR6+CCR7-). Similar to human MAITs, mouse MAITs expressed the cytokine receptors IL-7R, IL-18R?, and IL-12R? and the transcription factors promyelocytic leukemia zinc finger (PLZF) and RAR-related orphan receptor ? (ROR?t). Mouse MAITs produced Th1/2/17 cytokines upon TCR stimulation and recognized a bacterial compound in an MR1-dependent manner. During experimental urinary tract infection, MAITs migrated to the bladder and decreased bacterial load. Our study demonstrates that the MAIThi congenic strain allows phenotypic and functional characterization of naturally occurring mouse MAITs in health and disease.

SUBMITTER: Cui Y

PROVIDER: S-EPMC4639991 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

Cui Yue Y Franciszkiewicz Katarzyna K Mburu Yvonne K YK Mondot Stanislas S Le Bourhis Lionel L Premel Virginie V Martin Emmanuel E Kachaner Alexandra A Duban Livine L Ingersoll Molly A MA Rabot Sylvie S Jaubert Jean J De Villartay Jean-Pierre JP Soudais Claire C Lantz Olivier O

The Journal of clinical investigation 20151012 11

Mucosal-associated invariant T cells (MAITs) have potent antimicrobial activity and are abundant in humans (5%-10% in blood). Despite strong evolutionary conservation of the invariant TCR-α chain and restricting molecule MR1, this population is rare in laboratory mouse strains (≈0.1% in lymphoid organs), and lack of an appropriate mouse model has hampered the study of MAIT biology. Herein, we show that MAITs are 20 times more frequent in clean wild-derived inbred CAST/EiJ mice than in C57BL/6J m ...[more]

PMID: 26524590

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Project description:A recently identified unconventional T cell population known as mucosal-associated invariant T (MAIT) cells are characterized by the expression of semi-invariant T cell receptor (TCR) with a canonical TRAV1-2/TRAJ33 (Vα7.2/Jα33). These evolutionary conserved, innate-like T cells recognize vitamin B metabolites, derived from some bacteria and fungi. Due to their presence not only in the T cell repertoire of mucosal surfaces but also in peripheral blood and liver, and their significant involvement in a wide range of diseases, in-depth characterization of human MAIT cells is a timely requirement. Studies that examined the transcriptome, immunoproteome, and whole-cell proteome characterized the role of cytotoxic molecules and cytokines in effector functions of MAIT cells and their relationship with some other immune cell subsets. As MAIT cells are classified under the CD3+ T cell compartment and the majority express surface receptor CD8, identifying their proteomic relationship with CD3+ and CD8+ T cells is pivotal. Thus, a high-resolution dataset was generated using the cell populations sorted from peripheral blood mononuclear cells of three healthy volunteers to describe the whole cell proteomes of MAIT, CD3+, and CD8+ T cells. Trypsin-digested peptide samples obtained from the methanol co-precipitation method were analyzed using an Orbitrap FusionTM TribridTM mass spectrometer (Thermo Fisher Scientific, USA) inline coupled to nanoACQUITY ultra-performance liquid chromatography system (Waters, USA) to acquire data-dependent shotgun proteomic data (DDA-MS) for label-free quantification. Analysis of raw DDA-MS data using MaxQuant software and maxLFQ identified and quantified 4,442 protein groups at a 1% false discovery rate. Further analysis identified 3,680 proteins which were detected with a single UniProt accession and a minimum of 2 unique or razor peptides. Thus this proteomic dataset can be used as a reference proteome for future studies on human MAIT cells.

Dataset Information

Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

Publications

Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation.

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