Glycogen-fuelled metabolism supports rapid Mucosal Associated Invariant T cell responses

Abstract

Mucosal Associated Invariant T (MAIT) cells are a subset of unconventional T cells, which recognise a limited repertoire of ligands presented by the MHC class I-like molecule MR1. In addition to their key role in host protection against bacterial and viral pathogens, MAIT cells are emerging as potent anti-cancer effectors. With their abundance in human, unrestricted properties and rapid effector functions, MAIT cells are emerging as attractive candidates for cancer-immunotherapy. In the current study, we demonstrate that MAIT cells are potent anti-tumour cells, rapidly degranulating and inducing target cell death. Previous work from our group and others has highlighted glucose metabolism as a critical process for MAIT cell cytokine responses at 18 hours. However, the metabolic processes supporting rapid MAIT cell anti-tumour responses are currently unknown. Here, we show that glucose metabolism is dispensable for both MAIT cell cytotoxicity and early (<3 hours) cytokine production, as is oxidative phosphorylation. We show for the first time that MAIT cells have the machinery required to make and metabolize glycogen, and demonstrate that MAIT cell cytotoxicity and rapid cytokine responses are dependent on glycogen metabolism. In summary, we show for the first time that glycogen-fuelled metabolism supports rapid MAIT cell effector functions (cytotoxicity and cytokine production) which may have implications in their use as an immunotherapeutic agent.