Tracing MR1 expression across tissues to find the perfect MAIT

Abstract Mucosal associated invariant T (MAIT) cells are part of a T cell subset that is activated upon presentation of B2 vitamin (riboflavin) metabolites by the major histocompatibility complex, class I related (MR1) protein. Though there is a clear relationship between microbial production of riboflavin and MAIT cell development and persistence, little is known about the cells that primarily communicate with MAIT cells and other MR1-restricted T cells. Elegant work by Deng et al demonstrates that it is macrophages from the lung and peritoneum that express the highest amount of MR1 and are the most efficient at presenting vitamin B antigens to MAIT cells. This landmark study not only definitively identifies and maps the key antigen presenting cell populations involved in MAIT cell activation, it also reveals a bidirectional relationship between MR1 expression and the host microbiome. While further work on how these findings translate to human MAIT cell biology is needed, this study has provided us with unprecedented insights into the mechanistic interplay and microbial ecology of MR1 presentation of riboflavin metabolites.