Non Classical MHC presentation to Non-classical lymphocytesMR1-restricted T cell activation in physiopathology

Abstract

Similarly to iNKT cells, mucosal associated invariant T (MAIT) cells express an invariant TCRalpha chain with a limited number of beta chains. These innate-like T cells recognize bacterial ligands presented by the non-polymorphic MR1 molecule. Metabolites derived from bacterial riboflavin synthesis pathway activate MAIT cells to produce granzyme B, Th1 and Th17 cytokines. The recognition of bacterial ligands by MAIT cells is further illustrated by the near absence of MAIT cells in germ-free mice. Most interestingly the riboflavin precursor needs to be modified by small molecules such as methylglyoxal, which level is elevated in obesity and diabetes. Moreover gut micro- biota alterations have been described in diabetes and obesity, both in humans and mouse models. Our recent studies have shown major alterations of MAIT cells in the blood of obese and diabetic patients as compared to healthy lean control individuals, suggesting their potential role in these pathologies. On going studies on the role and activation of MAIT cells in these pathologies will be presented.