MAIT cells have been termed innate because they are restricted by the highly conserved MR1 antigen presentation molecule, and based on their limited TCR usage.  This concept is further reinforced by the discovery of riboflavin metabolites as key MR1 antigens for many microbes.  However, analysis of TCR usage in the context of particular microbial stimulation reveals selective TCR usage.  This observation supports the the hypothesis that MR1 presents a diverse array of ligands, and that these in turn are selectively recognized by MR1 restricted T cells (MR1Ts).  This hypothesis is further supported by the observation that MR1Ts present in the BAL of patients with TB are uniquely enriched relative to the peripheral blood.  To explore the ligandome of MR1 in the context of infection, the Adams laboratory enriched for microbial ligands by producing recombinant MR1 in the context of a microbial infection.  The Hildebrand laboratory then used tandem mass-spectrometry and molecular network analyses to visualize the array of MR1-presented microbial ligands and to subsequently identify several of these ligands.  Synthetic analogs of these newly identified MR1 microbial  ligands were tested for MR1 binding and for their capacity to activate MR1Ts with divergent TCR.  Our results unambiguously demonstrate the capacity of different TCRs to discriminate among MR1 ligands and support the hypothesis that microbial infection results in the selective expansion of MR1Ts.