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

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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 languageEnglish
Article number253
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 17 Jan 2018

Keywords

  • Antimicrobial responses
  • Infection
  • T-cell receptor

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