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Diverse MR1-restricted T cells in mice and humans

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Listed:
  • Hui-Fern Koay

    (University of Melbourne
    University of Melbourne)

  • Nicholas A. Gherardin

    (University of Melbourne
    University of Melbourne)

  • Calvin Xu

    (University of Melbourne)

  • Rebecca Seneviratna

    (University of Melbourne
    University of Melbourne)

  • Zhe Zhao

    (University of Melbourne)

  • Zhenjun Chen

    (University of Melbourne)

  • David P. Fairlie

    (The University of Queensland
    The University of Queensland)

  • James McCluskey

    (University of Melbourne)

  • Daniel G. Pellicci

    (University of Melbourne
    University of Melbourne
    Murdoch Children’s Research Institute)

  • Adam P. Uldrich

    (University of Melbourne
    University of Melbourne)

  • Dale I. Godfrey

    (University of Melbourne
    University of Melbourne)

Abstract

Mucosal-associated invariant T (MAIT) cells express an invariant TRAV1/TRAJ33 TCR-α chain and are restricted to the MHC-I-like molecule, MR1. Whether MAIT cell development depends on this invariant TCR-α chain is unclear. Here we generate Traj33-deficient mice and show that they are highly depleted of MAIT cells; however, a residual population remains and can respond to exogenous antigen in vitro or pulmonary Legionella challenge in vivo. These residual cells include some that express Trav1+ TCRs with conservative Traj-gene substitutions, and others that express Trav1- TCRs with a broad range of Traj genes. We further report that human TRAV1-2- MR1-restricted T cells contain both MAIT-like and non-MAIT-like cells, as judged by their TCR repertoire, antigen reactivity and phenotypic features. These include a MAIT-like population that expresses a public, canonical TRAV36+ TRBV28+ TCR. Our findings highlight the TCR diversity and the resulting potential impact on antigen recognition by MR1-restricted T cells.

Suggested Citation

  • Hui-Fern Koay & Nicholas A. Gherardin & Calvin Xu & Rebecca Seneviratna & Zhe Zhao & Zhenjun Chen & David P. Fairlie & James McCluskey & Daniel G. Pellicci & Adam P. Uldrich & Dale I. Godfrey, 2019. "Diverse MR1-restricted T cells in mice and humans," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10198-w
    DOI: 10.1038/s41467-019-10198-w
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