Human MR1-restricted T cells expressing TRAV12-2 display ligand discrimination — ASN Events
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Human MR1-restricted T cells expressing TRAV12-2 display ligand discrimination (#20)

Erin W Meermeier 1 , Bruno F Laugel 2 , Andrew K Sewell 2 , Alexandra J Corbett 3 , Jamie Rossjohn 2 4 , James McCluskey 3 , Melanie J Harriff 5 6 , Tamera Franks 6 , Marielle C Gold 1 5 6 , David M Lewinsohn 1 5 6
  1. Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA
  2. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
  3. Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, AU
  4. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, AU
  5. Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA
  6. VA Portland Health Care Center, Portland, OR, USA

MAIT cells are unconventional T cells that detect diverse microbial infections through antigens presented by MR1. MR1 can bind microbial riboflavin synthesis metabolites and these MR1 ligands activate MAIT cells. While MAIT cells have been defined by their expression of the TRAV1-2 TCRα, recent studies have demonstrated unexpected TCR heterogeneity. Here we confirmed the presence of functional human MR1-restricted T cells that did not express TRAV1-2 using ex-vivo analysis with mycobacteria-infected, MR1-deficient cells. We also determined that TRAV1-2 negative CD8+ T cells comprised 1-4% of the MR1-Ag tetramer+ population. Further, we isolated an MR1-restricted T cell clone that expressed the TRAV12-2 TCR and did not contain a CDR3α with amino acids previously shown to be critical for MR1-antigen recognition. In contrast to TRAV1-2+ MAIT cells, this clone detected Streptococcus pyogenes, a pathogen that cannot synthesize riboflavin. This study provides direct evidence for diversity of MAIT cells, novelty in MR1 ligands, and the ability of MAIT cells to discriminate between pathogens in a TCR dependent fashion. Thus, additional MAIT cell subsets may play a unique role in human defense against infection and compensate for the inability of TRAV1-2+ MAIT cells to recognize different microbial metabolites.