Lay summary
Mucosal-associated invariant T (MAIT) cells are immune cells that provide immunity against bacterial, fungal, and viral pathogens, but when dysregulated have been implicated in cancer, inflammation and autoimmune diseases. To be able to elicit an immune response, immature MAIT cells must first undergo a process called positive selection in the thymus. Positive selection requires self (endogenous) ligands activating immature MAIT cells. To date, nobody knows what these endogenous MAIT cell ligands are.
We will use highly innovative approaches to select and then screen endogenous metabolites for their ability to activate MAIT cells. If successful, this research will transform MAIT cell research. Our studies will provide much-needed insight into how MAIT cells can be manipulated for therapeutic applications that include cancer immunotherapy, as well as potentially allowing the negative impact of MAIT cells in autoimmune disease to be better mitigated.