MR1 presents microbial vitamin B metabolites to MAIT cells

@article{KjerNielsen2012MR1PM,
  title={MR1 presents microbial vitamin B metabolites to MAIT cells},
  author={Lars Kjer-Nielsen and Onisha Patel and Alexandra J. Corbett and J{\'e}r{\^o}me Le Nours and Bronwyn S. Meehan and Ligong Liu and Mugdha Bhati and Zhenjun Chen and Lyudmila Kostenko and Rangsima Reantragoon and Nicholas A. Williamson and Anthony Wayne Purcell and Nadine L. Dudek and Malcolm J. McConville and Richard A. J. O'hair and George N. Khairallah and Dale I. Godfrey and David P. Fairlie and Jamie Rossjohn and James McCluskey},
  journal={Nature},
  year={2012},
  volume={491},
  pages={717-723}
}
Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the… 
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963 Citations
Highly Influential Citations
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Background Citations
387
Methods Citations
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963 Citations

MR1 presentation of vitamin B-based metabolite ligands.
How MR1 Presents a Pathogen Metabolic Signature to Mucosal-Associated Invariant T (MAIT) Cells.
Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells*
TLDR
The understanding of how novel antigens are generated is reviewed and their interactions with MR1 and MAIT TCRs are discussed.
Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries
TLDR
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.
MHC class I‐related molecule, MR1, and mucosal‐associated invariant T cells
TLDR
The historical perspective of the MR1/MAIT field is provided before describing the main characteristics of MR1, its ligands, and the few available data regarding its cellular biology and the current knowledge of MAIT cell differentiation is summarized.
Mucosal‐associated invariant T cell receptor recognition of small molecules presented by MR1
TLDR
The key molecular interactions underlying the recognition and reactivity of MAIT TCRs to MR1 are defined in an Ag‐dependent manner and this metabolite Ag‐presenting molecule was shown to trap chemical scaffolds including drug and drug‐like molecules.
Recognition of vitamin B metabolites by mucosal-associated invariant T cells.
TLDR
A structural basis for MAIT TCR recognition of vitamin B metabolites is formally demonstrated, while illuminating how TCRs recognize microbial metabolic signatures.
The intracellular pathway for the presentation of vitamin B–related antigens by the antigen-presenting molecule MR1
TLDR
It is shown that MR1, unlike other antigen-presenting molecules, does not constitutively present self-ligands, and instead accumulates in a ligand-receptive conformation within the endoplasmic reticulum.
MR1 antigen presentation to MAIT cells: new ligands, diverse pathways?
T-cell activation by transitory neo-antigens derived from distinct microbial pathways
TLDR
It is shown that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis, and MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells.
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References

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Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells*
TLDR
Monoclonal antibodies were produced in MR1 knock-out mice immunized with recombinant MR1 protein, and a series of MR1 mutations were generated at sites previously shown to disrupt the ability of class Ia molecules to bind peptide or TCR, supporting the conclusion that MR1 has an antigen presentation function.
MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution
TLDR
It is shown that both mouse and human MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination, demonstrating that the presentation pathway of MR1 toMAIT cells is highly evolutionarily conserved.
MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells
TLDR
It is demonstrated that MR1 antigen presentation is not affected by either the proteasome or the class I chaperones, and the class II chaperone invariant chain, Ii, physically associates with MR1 and promotes its endosomal trafficking.
Endogenous MHC-Related Protein 1 Is Transiently Expressed on the Plasma Membrane in a Conformation That Activates Mucosal-Associated Invariant T Cells
TLDR
This article defines a unique mAb capable of stabilizing endogenous mouse MR1 at the cell surface, resulting in enhanced mouse MAIT cell activation and demonstrated that under basal conditions, endogenous MR1 transiently visits the cellsurface, thus reconciling the aforementioned serologic and functional studies.
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TLDR
Cloned bovine and ovine MR1 transcripts, including splice variants, and identified an anti human MR1 antibody that recognizes cells transfected with the bovines homolog and revealed that numbers of MAIT cells are low in neonates and increase by 3-weeks of age.
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TLDR
It is shown that T cells that express the canonical hVα7.2-Jα33 or mVα19-J α33 TCR rearrangement are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells.
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TLDR
MAIT cells are evolutionarily conserved innate-like lymphocytes that sense and help fight off microbial infection and protect against infection by Mycobacterium abscessus or Escherichia coli.
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TLDR
NKT cell biology has emerged as a new field of research at the frontier between innate and adaptive immunity, providing a powerful model to study fundamental aspects of the cell and structural biology of glycolipid trafficking, processing, and recognition.
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