MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1

López‐Sagaseta, Jacinto; Dulberger, Charles L.; McFedries, Amanda; Cushman, Mark; Saghatelian, Alan; Adams, Erin J.

doi:10.4049/jimmunol.1301958

Cited by 73 publications

(87 citation statements)

References 33 publications

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“…Although MAIT cell TCRs use preferential Vb segments, mutagenesis of individual residues within the CDRb regions indicates that the TCRb-chain of the MAIT cell TCRs did not play an important role in Ag reactivity, consistent with the lack of TCRb constraints (12,15). Altogether, the structural data are consistent with a limited number of MAIT cell ligands that do not fill the MR1 groove as they leave empty the F9 pocket (16,17). This opens the possibility of some level of complexity for MAIT cell ligands.…”

supporting

confidence: 56%

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In Vitro and In Vivo Analysis of the Gram-Negative Bacteria–Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells

Soudais¹,

Samassa²,

Sarkis³

et al. 2015

The Journal of Immunology

104

116

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Mucosal-associated invariant T (MAIT) cells recognize microbial compounds presented by the MHC-related 1 (MR1) protein. Although riboflavin precursor derivatives from Gram-positive bacteria have been characterized, some level of ligand heterogeneity has been suggested through the analysis of the MAIT cell TCR repertoire in humans and differential reactivity of human MAIT cell clones according to the bacteria. In this study, using Gram-negative bacteria mutated for the riboflavin biosynthetic pathway, we show a strict correlation between the ability to synthesize the 5-amino-ribityl-uracil riboflavin precursor and to activate polyclonal and quasi-monoclonal mouse MAIT cells. To our knowledge, we show for the first time that the semipurified bacterial fraction and the synthetic ligand activate murine MAIT cells in vitro and in vivo. We describe new MR1 ligands that do not activate MAIT cells but compete with bacterial and synthetic compounds activating MAIT cells, providing the capacity to modulate MAIT cell activation. Through competition experiments, we show that the most active synthetic MAIT cell ligand displays the same functional avidity for MR1 as does the microbial compound. Altogether, these results show that most, if not all, MAIT cell ligands found in Escherichia coli are related to the riboflavin biosynthetic pathway and display very limited heterogeneity.

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supporting

confidence: 56%

“…6B). It is likely that the acetyl group blocking the amine of the pterin in Cp-C and Cp-D stabilized the interaction of these compounds with MR1, leading to its upregulation (10,16).…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Analysis of the Gram-Negative Bacteria–Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells

Soudais¹,

Samassa²,

Sarkis³

et al. 2015

The Journal of Immunology

104

116

View full text Add to dashboard Cite

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“…Blocking experiments confirmed a requirement for butyrophilin 3A/CD277 for Vg9/Vd2 T cells and the MHC-related protein MR1 for MAIT cells (Fig. 1B), in support of current models of Ag recognition (41)(42)(43)(44)(45).…”

Section: Unconventional Human T Cells Respond To Neutrophil-released mentioning

confidence: 51%

“…Va7.2 + CD161 + MAIT cells show a very similar responsiveness to an overlapping, but distinct spectrum of microorganisms by sensing intermediates of the microbial vitamin B2 biosynthesis (Table I) (40)(41)(42)(43). We therefore sought to investigate the antimicrobial responses of these two types of unconventional T cells side by side.…”

Section: Unconventional Human T Cells Respond To Neutrophil-released mentioning

confidence: 99%

Microbe-Specific Unconventional T Cells Induce Human Neutrophil Differentiation into Antigen Cross-Presenting Cells

Davey

Kift-Morgan

Liuzzi

et al. 2014

The Journal of Immunology

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The early immune response to microbes is dominated by the recruitment of neutrophils whose primary function is to clear invading pathogens. However, there is emerging evidence that neutrophils play additional effector and regulatory roles. The present study demonstrates that human neutrophils assume antigen cross-presenting functions, and suggests a plausible scenario for the local generation of APC-like neutrophils through the mobilization of unconventional T-cells in response to microbial metabolites. Vγ9/Vδ2 T-cells and MAIT cells are abundant in blood, inflamed tissues and mucosal barriers. Here, both human cell types responded rapidly to neutrophils after phagocytosis of Gram-positive and Gram-negative bacteria producing the corresponding ligands, and in turn mediated the differentiation of neutrophils into APCs for both CD4+ and CD8+ T-cells through secretion of GM-CSF, IFN-γ and TNF-α. In patients with acute sepsis, circulating neutrophils displayed a similar APC-like phenotype and readily processed soluble proteins for cross-presentation of antigenic peptides to CD8+ T-cells, at a time when peripheral Vγ9/Vδ2 T-cells were highly activated. Our findings indicate that unconventional T-cells represent key controllers of neutrophil-driven innate and adaptive responses to a broad range of pathogens.

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“…[1][2][3][4] MAIT cells are uniquely activated by small molecule vitamin B metabolites presented by the ubiquitously expressed and non-polymorphic MHC-class 1-like molecule, MR1. [5][6][7][8][9] Circulating MAIT cells express certain phenotypic markers that have been used in varying combinations to identify them in human specimens: TRAV1-2, IL-18Ra, IL-23/12Ra, and high expression of both CD26 and CD161. 10,11 Use of different phenotypic definitions of MAIT cells has limited comparability of findings in the field.…”

Section: What Are Mait Cells and What Is Known About Their Phenotype mentioning

confidence: 99%

The role of mucosal‐associated invariant T cells in infectious diseases

2016

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SummaryMucosal-associated invariant T (MAIT) cells are donor-unrestricted lymphocytes that are surprisingly abundant in humans, representing 1-10% of circulating T cells and further enriched in mucosal tissues. MAIT cells recognize and are activated by small molecule ligands produced by microbes and presented by MR1, a highly conserved MHC-related antigen-presenting protein that is ubiquitously expressed in human cells. Increasing evidence suggests that MAIT cells play a protective role in anti-bacterial immunity at mucosal interfaces. Some fungi are known to produce MAIT-activating ligands, but the role of MAIT cells in fungal infections has not yet been investigated. In viral infections, specifically HIV, which has received the most study, MAIT cell biology is clearly altered, but the mechanisms explaining these alterations and their clinical significance are not yet understood. Many questions remain unanswered about the potential of MAIT cells for protection or pathogenesis in infectious diseases. Because they interact with the universal, donor-unrestricted ligand-presenting MR1 molecule, MAIT cells may be attractive immunotherapy or vaccine targets. New tools, including the development of MR1-ligand tetramers and next-generation T-cell receptor sequencing, have the potential to accelerate MAIT cell research and lead to new insights into the role of this unique set of lymphocytes in infectious diseases.

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MAIT Recognition of a Stimulatory Bacterial Antigen Bound to MR1

Cited by 73 publications

References 33 publications

In Vitro and In Vivo Analysis of the Gram-Negative Bacteria–Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells

In Vitro and In Vivo Analysis of the Gram-Negative Bacteria–Derived Riboflavin Precursor Derivatives Activating Mouse MAIT Cells

Microbe-Specific Unconventional T Cells Induce Human Neutrophil Differentiation into Antigen Cross-Presenting Cells

The role of mucosal‐associated invariant T cells in infectious diseases

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