Non-microbial metabolite antigens and T cell immune surveillance

Metabolite based T cell immunity is emerging as a major player in antimicrobial immunity, autoimmunity, cancer, and metabolic diseases. Initially, vitamin B-based derivatives, derived only from the microbial biosynthesis of riboflavin, 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 cells (MAIT) and diverse MR1-restricted T cells. More recently, we have begun to appreciate the diverse nature of the small molecule metabolites that can be displayed by MR1, with several less potent synthetic, drug and drug-like antigens being identified (*Salio, *Awad, et al. PNAS 2020). Using in-silico, immunological & structural approaches, this project will provide insights into the range of non-microbial chemical metabolites from the universe that can be presented by MR1, thus impact T cell immunity and host defence. Indeed, such studies improve our understanding of the molecular determinants of T cell immunity and pave the way for the development of innovative therapeutics based on selective modulation of MAIT cell immunity. 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.