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; Vincenzo Cerundolo

doi:10.1038/s41467-017-02540-x

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, Vincenzo Cerundolo

Biosciences

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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.

Original language	English
Article number	253
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-017-02540-x
Publication status	Published - 17 Jan 2018

Keywords

Antimicrobial responses
Infection
T-cell receptor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-017-02540-xLicence: Creative Commons: Attribution (CC BY)

Howson_et_al_MAIT_cell_clonal_expansion_Nature_CommunicationsFinal published version, 1.26 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Howson, L. J., Napolitani, G., Shepherd, D., Ghadbane, H., Kurupati, P., Preciado-Llanes, L., Rei, M., Dobinson, H. C., Gibani, M. M., Teng, K. W. W., Newell, E. W., Veerapen, N., Besra, G. S., Pollard, A. J., & Cerundolo, V. (2018). MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A. Nature Communications, 9, Article 253. https://doi.org/10.1038/s41467-017-02540-x

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

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.",

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author = "Howson, {Lauren J} and Giorgio Napolitani and Dawn Shepherd and Hemza Ghadbane and Prathiba Kurupati and Lorena Preciado-Llanes and Margarida Rei and Dobinson, {Hazel C} and Gibani, {Malick M} and Teng, {Karen Wei Weng} and Newell, {Evan W} and Natacha Veerapen and Besra, {Gurdyal S} and Pollard, {Andrew J} and Vincenzo Cerundolo",

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Howson, LJ, Napolitani, G, Shepherd, D, Ghadbane, H, Kurupati, P, Preciado-Llanes, L, Rei, M, Dobinson, HC, Gibani, MM, Teng, KWW, Newell, EW, Veerapen, N, Besra, GS, Pollard, AJ & Cerundolo, V 2018, 'MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A', Nature Communications, vol. 9, 253. https://doi.org/10.1038/s41467-017-02540-x

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T1 - MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A

AU - Howson, Lauren J

AU - Napolitani, Giorgio

AU - Shepherd, Dawn

AU - Ghadbane, Hemza

AU - Kurupati, Prathiba

AU - Preciado-Llanes, Lorena

AU - Rei, Margarida

AU - Dobinson, Hazel C

AU - Gibani, Malick M

AU - Teng, Karen Wei Weng

AU - Newell, Evan W

AU - Veerapen, Natacha

AU - Besra, Gurdyal S

AU - Pollard, Andrew J

AU - Cerundolo, Vincenzo

PY - 2018/1/17

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N2 - 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.

AB - 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.

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KW - Infection

KW - T-cell receptor

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