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MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A

Author

Listed:
  • Lauren J. Howson

    (University of Oxford)

  • Giorgio Napolitani

    (University of Oxford)

  • Dawn Shepherd

    (University of Oxford
    University of Oxford)

  • Hemza Ghadbane

    (University of Oxford
    Immunocore Ltd)

  • Prathiba Kurupati

    (University of Oxford)

  • Lorena Preciado-Llanes

    (University of Oxford)

  • Margarida Rei

    (University of Oxford)

  • Hazel C. Dobinson

    (University of Oxford and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre)

  • Malick M. Gibani

    (University of Oxford and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre)

  • Karen Wei Weng Teng

    (Singapore Immunology Network (SIgN))

  • Evan W. Newell

    (Singapore Immunology Network (SIgN))

  • Natacha Veerapen

    (University of Birmingham)

  • Gurdyal S. Besra

    (University of Birmingham)

  • Andrew J. Pollard

    (University of Oxford and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre)

  • Vincenzo Cerundolo

    (University of Oxford)

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function.

Suggested Citation

  • Lauren J. Howson & Giorgio Napolitani & Dawn Shepherd & Hemza Ghadbane & Prathiba Kurupati & Lorena Preciado-Llanes & Margarida Rei & Hazel C. Dobinson & Malick M. Gibani & Karen Wei Weng Teng & Evan , 2018. "MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02540-x
    DOI: 10.1038/s41467-017-02540-x
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