Projects per year
Mucosal-associated invariant T cells (MAIT cells) represent a potential therapeutic target as they can tune or enhance immune responses. They recognise and become activated by antigens, presented by the monomorphic MHC-I related molecule, MR1. To assess the significance of MAIT cells in human diseases, a better understanding of the MAIT cell-MR1-antigen interaction is imperative. Easy access to MR1 ligands and MAIT cells activators can help achieve this. In this review, we summarise current literature that has identified the natural ligands and drug-like molecules that activate MAIT cells and provide insight into their key molecular interactions with MR1 and MAIT T cell receptors (TCRs). We focus on the progress made in synthesizing and isolating 5-amino-6-d-ribitylaminouracil (5-A-RU), a key precursor in the synthesis of the known natural ligands, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil(5-OP-RU) and 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and also on the stabilisation and optimisation of the latter compounds.
Bibliographical noteFunding Information:
GSB acknowledges support in the form of a Personal Research Chair from Mr. James Bardrick, a R oyal Society Wolfson Research Merit Award , and the Medical Research Council, UK (MR/R001154/1 and MR/S000542/1).
- MAIT activation
- MR1 upregulation
- Polar interaction
- Schiff base
- TCR recognition
ASJC Scopus subject areas
- Molecular Biology
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MICA: Addressing the burgeoning problem of tuberculosis: Exploiting phenotypic hits to identify new protein targets for drug discovery
1/04/18 → 31/03/22
Project: Research Councils