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

Nat Commun. 2018 Jan 17;9(1):253. doi: 10.1038/s41467-017-02540-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Line, Tumor
  • Cell Proliferation*
  • Clone Cells / immunology
  • Clone Cells / metabolism
  • Clone Cells / microbiology
  • Healthy Volunteers
  • Host-Pathogen Interactions / immunology
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / microbiology
  • Middle Aged
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Mucosal-Associated Invariant T Cells / microbiology
  • Paratyphoid Fever / immunology*
  • Paratyphoid Fever / metabolism
  • Paratyphoid Fever / microbiology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Salmonella paratyphi A / immunology*
  • Salmonella paratyphi A / physiology
  • Young Adult

Substances

  • Receptors, Antigen, T-Cell, alpha-beta