Events

23 Feb 2017

Drugs and drug-like molecules can modulate the function of MAIT cells

Dr Sidonia Eckle from the University of Melbourne will speak to Drugs and drug-like molecules can modulate the function of MAIT cells.

Mucosal Associated Invariant T (MAIT) cells are an abundant subset of T cells, whose T cell receptor is restricted by the monomorphic MHC class I related molecule MR1. Acting as signature biomarkers of microbial infection, stimulating MAIT cell antigens, such as 5-OP-RU, originate from the microbial biosynthesis of vitamin B2. MR1 also binds vitamin B9 derived non-stimulating ligands, which act as competitive inhibitors of stimulating antigens. Whether MR1 binds other ligands is unknown.Given the small molecule nature of MR1 ligands identified thus far, we reasoned that drugs and drug-like molecules could represent a source of exogenous MR1 ligands. Indeed when screening a library of drugs and drug-like molecules in vitro, we identified novel MR1 ligands. Some of these inhibited human MAIT cell activity in response to 5-OP-RU in vitro and ex vivo and mouse MAIT cell activity in vivo. Additionally, a drug and metabolites thereof activated a subset of MAIT cells in an MR1-restricted manner in vitro.Thus MR1 can capture a range of chemically diverse ligands and other naturally occurring MR1 ligands beyond vitamin B metabolites might exist. In addition our findings suggest that widely used drugs have the potential to modulate MAIT cell function and there could be a link to not completely understood pharmacological responses and intolerances to drugs. At the same time these findings also point to the potential of modulating MAIT cells therapeutically by small molecule MR1 ligands.

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