MAIT, MR1, microbes and riboflavin: a paradigm for the co-evolution of invariant TCRs and restricting MHCI-like...

MAIT cells express an invariant TCR that recognizes non-peptidic microbial antigens presented by the non-polymorphic MHCI-like molecule, MR1. We briefly describe how the antigens recognized by MAIT cells are generated from an unstable precursor of the riboflavin (Vitamin B2) biosynthesis pathway, as well as the main features of MAIT cells in comparison with other related T cell subsets. In silico analysis of bacterial genomes shows that the riboflavin biosynthesis pathway is highly prevalent in all groups of Prokaryotes with, however, notable exceptions. We discuss the putative functions and the evolution of the MAIT/MR1 couple: it appeared in the ancestors of mammals and is highly conserved across this group, but was independently lost in three orders. We describe the four instances of known invariant TCR and MHC-I-like molecules encountered in Vertebrates. Both T cells bearing semi-invariant TCR and the associated, evolutionarily conserved MHC-I related molecules have been found in mammals or in amphibians, which suggests that other MHC1-like/invariant TCR couples might be present in other classes of Vertebrates to detect generic microbial compounds. This allows us to discuss how the recognition of riboflavin precursor derivatives by the MAIT TCR may be a way to detect invasive microbes in specific organs, and may epitomize other invariant T cell systems across vertebrates.