Identification and characterisation of a diverse repertoire of atypical MR1-restricted T cells — ASN Events
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Identification and characterisation of a diverse repertoire of atypical MR1-restricted T cells (#21)

Nicholas A Gherardin 1 , Andrew N Keller 2 , Rachel E Woolley 2 , Jérôme Le Nours 2 3 , Paul J Neeson 4 , David S Ritchie 4 , Richard W Birkinshaw 2 3 , Sidonia BG Eckle 1 , Ligong Liu 3 5 , Daniel G Pellicci 1 , Adam P Uldrich 1 3 , David P Fairlie 3 5 , James McCluskey 1 , Jamie Rossjohn 2 3 6 , Dale I Godfrey 1 3
  1. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  3. ARC Centre of Excellence in Advanced Molecular Imaging, Australia
  4. Cancer Immunology Program, Peter McCallum Cancer Centre, East Melbourne, VIC, Australia
  5. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia
  6. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK

Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved population of innate-like T cells1  . MAIT cells recognise antigens (Ags) derived from the microbial vitamin B2 metabolism pathway, presented by the monomorphic MHC-related protein 1 (MR1)2 5 6 . While their specific physiological role remains unresolved, MAIT cells are emerging as key players in anti-microbial immunity3 4 .

Whether the semi-invariant MAIT T cell receptor (TCR) can recognise non-microbial-derived Ags remains unknown. Furthermore, whether MR1-mediated T cell immunity can be orchestrated by T cells other than MAIT cells is unexplored. Here, using MR1-Ag loaded tetramers8  we show that the MR1-restricted T cell TCR repertoire is highly variable. This diverse repertoire encompasses both TRAV1-2POS and TRAV1-2NEG T cells, and includes cells restricted to riboflavin- and/or folate (Vitamin B9)-derivative Ags. Furthermore, these cells utilise docking modes atop MR1 that diverge from the pattern-recognition-like features of semi-invariant MAIT TCRs7 .

Accordingly, we describe a diverse population of atypical MR1-restricted T cells. We provide data on the phenotype and TCR repertoire of these cells, as well as providing molecular insight into atypical TCR gene usage in the MR1-restricted T cell repertoire.

This work provides a basis for a role for MR1-mediated T cell immunity beyond that of the MAIT-MR1-riboflavin axis. 

  1. Tilloy F, et al. An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammals. The Journal of experimental medicine 1999
  2. Treiner E, et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 2003
  3. Le Bourhis L, et al. Antimicrobial activity of mucosal-associated invariant T cells. Nature Immunology 2010
  4. Gold MC, et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS biology 2010
  5. Kjer-Nielsen L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 2012
  6. Corbett AJ, et al. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 2014
  7. Eckle SBG, et al. A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells. The Journal of Experimental Medicine 2014.
  8. Reantragoon R, et al. Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. The Journal of experimental medicine 2013