Exploring metabolite driving diversity within human MR1-restricted T cells

Metabolite based T cell immunity is emerging as a major player in antimicrobial immunity, autoimmunity, metabolic diseases, and cancer. Namely, vitamin B-based derivatives were identified to be captured and presented by the major histocompatibility complex (MHC) class-I related molecule MR1 to T cells, namely Mucosal Associated Invariant T (MAIT) cells. While the αβ MAIT cells with their semi-invariant TRAV1-2+ T cell repertoire constitute the majority of these unconventional T cells, We and other research groups have discovered a diverse population of atypical (TRAV1-2-) αβ T cells that exhibited selective reactivity toward metabolic antigens associated with MR1 (Science 2019 & JBC 2020). This project will tackle the molecular basis underpinning the reactivity and selectivity of the atypical MR1-restricted T cells toward diverse families of metabolic ligands including folate, and riboflavin antigens. Our underlying approach is to express and purify proteins, and determine the 3D structure using the expertise in x-ray crystallography. These are complemented by multi-disciplinary and highly innovative approaches including Surface Plasmon Resonance (SPR), Mass Spectrometry (MS), cellular immunology and advanced atomic and molecular imaging where required.