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

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 W. Newell, Natacha Veerapen, Gurdyal S. Besra, Andrew J. Pollard and Vincenzo Cerundolo ()
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Lauren J. Howson: University of Oxford
Giorgio Napolitani: University of Oxford
Dawn Shepherd: University of Oxford
Hemza Ghadbane: University of Oxford
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

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-017-02540-x

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