Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses

Giorgio Napolitani, Prathiba Kurupati, Karen Wei Weng Teng, Malick M. Gibani, Margarida Rei, Anna Aulicino, Lorena Preciado-Llanes, Michael Thomas Wong, Etienne Becht, Lauren Howson, Paola De Haas, Mariolina Salio, Christoph J. Blohmke, Lars Rønn Olsen, David Miguel Susano Pinto, Laura Scifo, Claire Jones, Hazel Dobinson, Danielle Campbell, Helene B. JuelHelena Thomaides-Brears, Derek Pickard, Dirk Bumann, Stephen Baker, Gordon Dougan, Alison Simmons, Melita A. Gordon, Evan William Newell, Andrew J. Pollard, Vincenzo Cerundolo

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

To tackle the complexity of cross-reactive and pathogen-specific T cell responses against related Salmonella serovars, we used mass cytometry, unbiased single-cell cloning, live fluorescence barcoding, and T cell-receptor sequencing to reconstruct the Salmonella-specific repertoire of circulating effector CD4+ T cells, isolated from volunteers challenged with Salmonella enterica serovar Typhi (S. Typhi) or Salmonella Paratyphi A (S. Paratyphi). We describe the expansion of cross-reactive responses against distantly related Salmonella serovars and of clonotypes recognizing immunodominant antigens uniquely expressed by S. Typhi or S. Paratyphi A. In addition, single-amino acid variations in two immunodominant proteins, CdtB and PhoN, lead to the accumulation of T cells that do not cross-react against the different serovars, thus demonstrating how minor sequence variations in a complex microorganism shape the pathogen-specific T cell repertoire. Our results identify immune-dominant, serovar-specific, and cross-reactive T cell antigens, which should aid in the design of T cell-vaccination strategies against Salmonella.

Original languageEnglish
Pages (from-to)742-754
Number of pages13
JournalNature Immunology
Volume19
Issue number7
DOIs
Publication statusPublished - 20 Jun 2018
Externally publishedYes

Keywords

  • bacterial infection
  • cellular immunity

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