Alternative splicing of MR1 regulates T cell responses to mycobacteria Public Deposited

MR1-restricted T (MR1T) cells are part of a growing class of unconventional T cells that have emerged as important players in the early response to microbial infection. These cells, like other unconventional T cells, not only emerge from the thymus with immediate effector function, but also recognize non-peptide antigen produced by microbes. Importantly, this represents a paradigm by which unconventional T cells can sample the environment to detect infection, broadening the scope of antigen generated by microbial infection. MR1T cells, in particular, recognize small molecule antigen produced as intermediates in the Vitamin B biosynthesis pathway, introducing an effective means of detecting self-from non-self. The MR1T T cell receptor was originally thought to be semi-invariant and recognize a conserved array of ligands. Recent evidence suggests a wide range of diversity in the MR1T TCR, and this diversity can contribute to detection of a broader range of small molecules, including those distinct from those in the riboflavin synthesis pathway. Additionally, the importance of the MR1T TCRa and TCRb chains in the recognition of antigen is not known. We show, using a panel of MR1T clones that share TCRa with differing TCRb chains, that the MR1T TCRb chain can contribute to recognition of both microbially infected dendritic cells, as well as distinguish between microbial ligand. These results suggest an important role in the TCRb chain in helping to sense microbial infection. However, given the wide range of antigen recognized by MR1T cells, as well as their capacity to produce inflammatory cytokines, and their enrichment in mucosal sites, likely in close proximity to commensals also capable of producing MR1T antigen, the question remains on how MR1T cell activation is regulated to prevent unwanted tissue damage or autoimmunity.

  • gitanjali.narayanan.2019.pdf
Publication Date
  • 2019
Document type