MAIT cell-MR1 reactivity is highly conserved across multiple divergent species

Matthew D Edmans, Timothy K Connelley, Sophie Morgan, Troi J Pediongco, Siddharth Jayaraman, Jennifer A Juno, Bronwyn S Meehan, Phoebe M Dewar, Emmanuel A Maze, Eduard O Roos, Basu Paudyal, Jeffrey Yw Mak, Ligong Liu, David P Fairlie, Huimeng Wang, Alexandra J Corbett, James McCluskey, Lindert Benedictus, Elma Tchilian, Paul KlenermanSidonia Bg Eckle

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Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T cells that recognize small molecule metabolites presented by major histocompatibility complex class I related protein 1 (MR1), via an αβ T cell receptor (TCR). MAIT TCRs feature an essentially invariant TCR α-chain, which is highly conserved between mammals. Similarly, MR1 is the most highly conserved major histocompatibility complex-I–like molecule. This extreme conservation, including the mode of interaction between the MAIT TCR and MR1, has been shown to allow for species-mismatched reactivities unique in T cell biology, thereby allowing the use of selected species-mismatched MR1–antigen (MR1–Ag) tetramers in comparative immunology studies. However, the pattern of cross-reactivity of species-mismatched MR1–Ag tetramers in identifying MAIT cells in diverse species has not been formally assessed. We developed novel cattle and pig MR1–Ag tetramers and utilized these alongside previously developed human, mouse, and pig-tailed macaque MR1–Ag tetramers to characterize cross-species tetramer reactivities. MR1–Ag tetramers from each species identified T cell populations in distantly related species with specificity that was comparable to species-matched MR1–Ag tetramers. However, there were subtle differences in staining characteristics with practical implications for the accurate identification of MAIT cells. Pig MR1 is sufficiently conserved across species that pig MR1–Ag tetramers identified MAIT cells from the other species. However, MAIT cells in pigs were at the limits of phenotypic detection. In the absence of sheep MR1–Ag tetramers, a MAIT cell population in sheep blood was identified phenotypically, utilizing species-mismatched MR1–Ag tetramers. Collectively, our results validate the use and define the limitations of species-mismatched MR1–Ag tetramers in comparative immunology studies.

Original languageEnglish
Article number107338
JournalJournal of Biological Chemistry
Issue number6
Early online date3 May 2024
Publication statusPublished - Jun 2024


  • 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU)
  • Antigen (Ag)
  • Comparative immunology
  • Innate-like immunity
  • MHC-I related protein 1 (MR1)
  • Major Histocompatibility Complex (MHC)
  • Mucosal-associated invariant T (MAIT) cell
  • T cell biology
  • T cell receptor (TCR)


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