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

Research output: Contribution to journalJournal article – Annual report year: 2018Researchpeer-review

  • Author: Napolitani, Giorgio

    University of Oxford, United Kingdom

  • Author: Kurupati, Prathiba

    University of Oxford, United Kingdom

  • Author: Teng, Karen Wei Weng

    Agency for Science, Technology and Research, Singapore

  • Author: Gibani, Malick M.

    University of Oxford, United Kingdom

  • Author: Rei, Margarida

    University of Oxford, United Kingdom

  • Author: Aulicino, Anna

    University of Oxford, United Kingdom

  • Author: Preciado-Llanes, Lorena

    University of Oxford, United Kingdom

  • Author: Wong, Michael Thomas

    Agency for Science, Technology and Research, Singapore

  • Author: Becht, Etienne

    Agency for Science, Technology and Research, Singapore

  • Author: Howson, Lauren J.

    University of Oxford, United Kingdom

  • Author: de Haas, Paola

    University of Oxford, United Kingdom

  • Author: Salio, Mariolina

    University of Oxford, United Kingdom

  • Author: Blohmke, Christoph J.

    University of Oxford, United Kingdom

  • Author: Olsen, Lars Rønn

    Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Pinto, David Miguel Susano

    University of Oxford, United Kingdom

  • Author: Scifo, Laura

    University of Oxford, United Kingdom

  • Author: Jones, Claire

    University of Oxford, United Kingdom

  • Author: Dobinson, Hazel

    University of Oxford, United Kingdom

  • Author: Campbell, Danielle

    University of Oxford, United Kingdom

  • Author: Juel, Helene B.

    University of Oxford, United Kingdom

  • Author: Thomaides-Brears, Helena

    University of Oxford, United Kingdom

  • Author: Pickard, Derek

    Wellcome Sanger Institute, United Kingdom

  • Author: Bumann, Dirk

    University of Basel, Switzerland

  • Author: Baker, Stephen

    Oxford University Clinical Research Unit, Viet Nam

  • Author: Dougan, Gordon

    Wellcome Sanger Institute, United Kingdom

  • Author: Simmons, Alison

    University of Oxford, United Kingdom

  • Author: Gordon, Melita A.

    University of Liverpool, United Kingdom

  • Author: Newell, Evan William

    Agency for Science, Technology and Research, Singapore

  • Author: Pollard, Andrew J.

    University of Oxford, United Kingdom

  • Author: Cerundolo, Vincenzo

    University of Oxford, United Kingdom

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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
JournalNature Immunology
Volume19
Issue number7
Pages (from-to)1-13
Number of pages13
ISSN1529-2908
DOIs
Publication statusPublished - 2018
CitationsWeb of Science® Times Cited: No match on DOI

ID: 150475423