Bacteria, mucosal‐associated invariant T cells and MR1

Abstract

Certain subpopulations of T lymphoctyes show innate-like properties that distinguish them from conventional T cells and thus have been collectively termed innate T cells. Two extensively studied subsets of innate T cells implicated in pathogen detection are invariant natural killer T (iNKT) cells and γδ T cells. Conventional T cells detect pathogens in a manner that is exquisitely antigen specific, based on discrimination of peptides bound to classical major histocompatibility complex (MHC) molecules. By contrast, innate T cells have only limited antigen discrimination and when antigen presentation has been implicated the antigen is not an unmodified peptide. For example, iNKT cells are activated by lipids presented by CD1d molecules,1 whereas certain γδ T cells are directly activated by ‘danger signals’ such as the small microbial product isopentenyl pyrophosphate.2 Their limited ligand discrimination and relatively larger clonal size allow innate T cells to mount earlier responses than conventional T cells. In comparison with conventional T cells, innate T-cell populations develop by a distinct ontogenic pathway and preferentially home to specific tissues. On the basis of these combined properties of innate T cells and the fact that their receptors and ligands have been highly conserved in evolution, it is attractive to propose that they represent ancient innate pathways of pathogen protection. Mucosal-associated invariant T (MAIT) cells were previously shown to have several properties in common with innate T cells, yet their physiological function remained unknown. Two new articles, Le Bourhis et al. published in Nature Immunology3 (reviewed here) and Gold et al. published in PLoS Biology4 implicate MAIT cells in the detection of bacterial infection in a manner restricted by the novel MHC class I-related molecule, MR1.