@article{Antimicrobial:6525,
      recid = {6525},
      author = {Ladd, Nicole Anna},
      title = {Molecular and Cellular Diversity of the MR1-MR1T Cell Axis  in Antimicrobial Immunity},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2023-06},
      abstract = {In lieu of peptides, the monomorphic MHC-I-like molecule  MR1 is thought to present small molecule antigens to  stimulate a semi-invariant, phenotypically distinct subset  of ɑβ T cells called MR1-restricted T (MR1T) cells. The MR1  ligands identified to date derive from the riboflavin  biosynthesis pathway and their presentation is therefore  thought to be an indicator of bacterial infection,  including that of Mycobacterium tuberculosis. The MR1-MR1T  cell axis was once thought to be a highly conserved,  innate-like immune mechanism due to the monomorphic nature  of MR1, the small pool of validated ligands, and the bias  toward usage of a single TRAV gene by a subset of MR1T  cells. However, the data presented in this thesis suggest  that the MR1-MR1T cell axis is not a binary sensor of  infection, but rather a complex indicator of the cellular  metabolome; specifically, this work expands our  understanding of the molecular mechanisms underpinning  donor-unrestricted T cell biology. In this thesis, I first  describe a mass spectrometry-based platform for the  investigation of the bacterially-derived ligand repertoire  of MR1 which revealed a novel class of  indolyl-ribityllumazine MR1 ligands. I then present a case  study on MR1T cell selectivity by contrasting MR1T cell  clone responses toward a natural ribityllumazine MR1 ligand  and its deaza-analogue. Finally, I explore heterogeneity in  the TCR diversity, antigen specificity, and phenotype of  MR1T cells from the peripheral blood of healthy donors  using single-cell multi-omics techniques. Altogether, this  work addresses the diversity of MR1-restricted T cell  antigen recognition and in doing so, challenges the  paradigms of MR1T cell biology.},
      url = {http://knowledge.uchicago.edu/record/6525},
      doi = {https://doi.org/10.6082/uchicago.6525},
}