In humans, MAIT cells are absent from the blood of those with TB and sepsis.  While these data suggest a relationship between microbial infection and MAIT cell recognition, whether or not this recognition is the result of recognition of a single ligand or ligand family, or multiple discrete ligands is less clear.  The answer to these questions has the potential to address whether MAIT cells have features of immunologic memory, namely antigen-driven clonal expansions reflective of antigenic exposure and persistence.

To address this question, we have taken three approaches:

1)     Analysis of lung resident MAIT cells in the context of infection with M. tuberculosis.  We find that pulmonary tuberculosis is associated with substantial enrichments of pro-inflammatory MAIT cells in the BAL fluid, which appear to be oligoclonal.  Furthermore, analysis of TCR usage in the granuloma reveals both public TCRs, and private TCRs unique to one individual.

2)     Analysis of microbial reactive MAIT cells. TCR usage of MAIT cells derived from 4 individuals in response to 3 different pathogens (M.smegmatis, S. typhimurium, and C. albicans) demonstrated unexpectedly diverse TRAV usage. While common TRAV1-2 CDR3 sequences were observed across multiple donors, the TRAV chain repertoire, within a given individual, displayed selective microbial reactivity.

3)     Analysis of TRAV1-2 negative MAIT cells.  We find evidence of MAIT cells that are TRAV1-2 negative that display a unique pattern of microbial recognition. Most strikingly, these cells can recognize infection due to S. pyogenes, a microbe incapable of riboflavin biosynthesis.

These data, then, provide increasing evidence for selective TCR usage associated with ligand discrimination, and provide support for the hypothesis that MAIT cells have immunologic memory.

Grant Support:

Funding was provided in part by the Department of Veterans Affairs and with resources and the use of facilities at the Portland VA Medical Center, National Institutes of Health (NIH) grant AI095776, under the NIAID funded MIST Consortium (mucosal.org) as well as the NIAID grant AI046553.