Molecular mechanisms of lineage decisions in metabolite-specific T cells

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

doi:10.1038/s41590-019-0465-3

Cited by 80 publications

(130 citation statements)

References 42 publications

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“…In naïve mice, we observed a skewed composition of transcriptional expression according to tissue sites; with greater proportions of MAIT-1 cells in the liver, MAIT-17 cells in the lungs and similar proportions of MAIT-1 and MAIT-17 cells in the kidney, spleen and blood. Consistent with previous reports 43,44,45 , this observation strongly suggests tissue specific imprints can favour one phenotype of MAIT cells. Surprisingly, infection with F. tularensis LVS resulted in a marked polarization to a MAIT-1 response, regardless of the tissue location.…”

Section: Systemically Boosted Mait-1 Cells Manifest Vaccination Potensupporting

confidence: 92%

“…7, G) indicating that vaccination to boost MAIT cells can provide a level of protection against unrelated bacterial pathogens. Mouse MAIT cells were previously reported to egress the thymus with mutually-exclusive MAIT-1 or MAIT-17 effector phenotypes 43,44 , which correlate with T-bet and RORgt expression, respectively. In naïve mice, we observed a skewed composition of transcriptional expression according to tissue sites; with greater proportions of MAIT-1 cells in the liver, MAIT-17 cells in the lungs and similar proportions of MAIT-1 and MAIT-17 cells in the kidney, spleen and blood.…”

Section: Systemically Boosted Mait-1 Cells Manifest Vaccination Potenmentioning

confidence: 99%

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Priming programed Mucosal-Associated Invariant T cells protect against systemic or local bacterial infection

Zhao

Shi

Zhu

et al. 2020

Preprint

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Mucosal-Associated Invariant T (MAIT) cells have potent antibacterial functions. Their protective capacity, in vivo, has been demonstrated in mouse models, particularly of respiratory infections. We now show that during systemic infection of mice with Francisella tularensis Live Vaccine Strain (LVS), MAIT cell expansion was evident in the liver, lungs, kidney, spleen and blood. MAIT cells manifested a polarised Th1-like (termed “MAIT-1”) phenotype and cytokine profile that conferred a critical role in controlling bacterial load. After resolution of the primary infection, the expanded MAIT cells developed to a stable memory-like MAIT-1 cell population, suggesting a basis for vaccination and protection against subsequent challenge. Indeed, a systemic vaccination with synthetic ligand (5-OP-RU) in combination with CpG adjuvant boosted MAIT-1 cells and resulted in enhanced protection against systemic and local infections with F. tularensis and Legionella longbeachae. Our study highlights the potential utility of targeting MAIT cells to combat multiple bacterial pathogens.

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Section: Systemically Boosted Mait-1 Cells Manifest Vaccination Potensupporting

confidence: 92%

Section: Systemically Boosted Mait-1 Cells Manifest Vaccination Potenmentioning

confidence: 99%

Priming programed Mucosal-Associated Invariant T cells protect against systemic or local bacterial infection

Zhao

Shi

Zhu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Models of infection with bacterial pathogens in mice ( 32 – 34 , 54 ) and non-human primates ( 147 ) have revealed much about MAIT cell biology and their role in protective immunity. The development of MR1-5-OP-RU-tetramer reagents ( 7 , 11 ) has enabled the specific assessment of MAIT cells in naïve SPF-housed mice ( 67 , 130 , 148 ), in disease-relevant models including infection, autoimmune disease ( 35 , 149 , 150 ), transplantation ( 151 ) and cancer ( 152 ), and MAIT cell development ( 55 , 71 , 153 ). MR1-tetramers also allow the assessment of the ability of defined compounds to act as antigens, with 5-OP-RU ( 67 , 93 ), premixed 5-A-RU and methylglyoxal ( 25 , 123 ) and a pro-drug designed to release 5-A-RU ( 123 ) all shown to boost MAIT cell numbers in mice, in the presence of TLR agonists or other co-stimuli.…”

Section: Tools For the Assessment Of Mr1 Ligand Production And Recognmentioning

confidence: 99%

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

et al. 2020

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Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2 + cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo . The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.

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“…63 Similarly, in Mus musculus castaneus (CAST mice), modified to lack MR1, a small population of TRAV1-TRAJ33 expressing cells was identified that was selected by other MHC molecules, possibly MHC-II molecules. 64…”

Section: Chromium 115mentioning

confidence: 99%

Hypersensitivities following allergen antigen recognition by unconventional T cells

Moreira

Souter

Chen

et al. 2020

Allergy

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Conventional T cells recognise protein-derived antigens in the context of major histocompatibility complex (MHC) class Ia and class II molecules and provide anti-microbial and anti-tumour immunity. Conventional T cells have also been implicated in type IV (also termed delayed-type or T cell-mediated) hypersensitivity reactions in response to protein-derived allergen antigens. In addition to conventional T cells, subsets of unconventional T cells exist, which recognise non-protein antigens in the context of monomorphic MHC class I-like molecules. These include T cells that are restricted to the cluster of differentiation 1 (CD1) family members, known as CD1restricted T cells, and mucosal-associated invariant T cells (MAIT cells) that are restricted to the MHC-related protein 1 (MR1). Compared with conventional T cells, much less is known about the immune functions of unconventional T cells and their role in hypersensitivities. Here, we review allergen antigen presentation by MHC-Ilike molecules, their recognition by unconventional T cells, and the potential role of unconventional T cells in hypersensitivities. We also speculate on possible scenarios of allergen antigen presentation by MHC-I-like molecules to unconventional T cells, the hallmarks of such responses, and the expected frequencies of hypersensitivities within the human population.

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Molecular mechanisms of lineage decisions in metabolite-specific T cells

Cited by 80 publications

References 42 publications

Priming programed Mucosal-Associated Invariant T cells protect against systemic or local bacterial infection

Priming programed Mucosal-Associated Invariant T cells protect against systemic or local bacterial infection

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries

Hypersensitivities following allergen antigen recognition by unconventional T cells

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