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. Juel & 10 others Helena 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

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

Cite this

Napolitani, G., Kurupati, P., Teng, K. W. W., Gibani, M. M., Rei, M., Aulicino, A., ... Cerundolo, V. (2018). Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses. Nature Immunology, 19(7), 742-754. https://doi.org/10.1038/s41590-018-0133-z
Napolitani, Giorgio ; Kurupati, Prathiba ; Teng, Karen Wei Weng ; Gibani, Malick M. ; Rei, Margarida ; Aulicino, Anna ; Preciado-Llanes, Lorena ; Wong, Michael Thomas ; Becht, Etienne ; Howson, Lauren ; De Haas, Paola ; Salio, Mariolina ; Blohmke, Christoph J. ; Olsen, Lars Rønn ; Pinto, David Miguel Susano ; Scifo, Laura ; Jones, Claire ; Dobinson, Hazel ; Campbell, Danielle ; Juel, Helene B. ; Thomaides-Brears, Helena ; Pickard, Derek ; Bumann, Dirk ; Baker, Stephen ; Dougan, Gordon ; Simmons, Alison ; Gordon, Melita A. ; Newell, Evan William ; Pollard, Andrew J. ; Cerundolo, Vincenzo. / Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses. In: Nature Immunology. 2018 ; Vol. 19, No. 7. pp. 742-754.
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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.",
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author = "Giorgio Napolitani and Prathiba Kurupati and Teng, {Karen Wei Weng} and Gibani, {Malick M.} and Margarida Rei and Anna Aulicino and Lorena Preciado-Llanes and Wong, {Michael Thomas} and Etienne Becht and Lauren Howson and {De Haas}, Paola and Mariolina Salio and Blohmke, {Christoph J.} and Olsen, {Lars R{\o}nn} and Pinto, {David Miguel Susano} and Laura Scifo and Claire Jones and Hazel Dobinson and Danielle Campbell and Juel, {Helene B.} and Helena Thomaides-Brears and Derek Pickard and Dirk Bumann and Stephen Baker and Gordon Dougan and Alison Simmons and Gordon, {Melita A.} and Newell, {Evan William} and Pollard, {Andrew J.} and Vincenzo Cerundolo",
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Napolitani, G, Kurupati, P, Teng, KWW, Gibani, MM, Rei, M, Aulicino, A, Preciado-Llanes, L, Wong, MT, Becht, E, Howson, L, De Haas, P, Salio, M, Blohmke, CJ, Olsen, LR, Pinto, DMS, Scifo, L, Jones, C, Dobinson, H, Campbell, D, Juel, HB, Thomaides-Brears, H, Pickard, D, Bumann, D, Baker, S, Dougan, G, Simmons, A, Gordon, MA, Newell, EW, Pollard, AJ & Cerundolo, V 2018, 'Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses' Nature Immunology, vol. 19, no. 7, pp. 742-754. https://doi.org/10.1038/s41590-018-0133-z

Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses. / Napolitani, Giorgio; Kurupati, Prathiba; Teng, Karen Wei Weng; Gibani, Malick M.; Rei, Margarida; Aulicino, Anna; Preciado-Llanes, Lorena; Wong, Michael Thomas; Becht, Etienne; Howson, Lauren; De Haas, Paola; Salio, Mariolina; Blohmke, Christoph J.; Olsen, Lars Rønn; Pinto, David Miguel Susano; Scifo, Laura; Jones, Claire; Dobinson, Hazel; Campbell, Danielle; Juel, Helene B.; Thomaides-Brears, Helena; Pickard, Derek; Bumann, Dirk; Baker, Stephen; Dougan, Gordon; Simmons, Alison; Gordon, Melita A.; Newell, Evan William; Pollard, Andrew J.; Cerundolo, Vincenzo.

In: Nature Immunology, Vol. 19, No. 7, 20.06.2018, p. 742-754.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Napolitani, Giorgio

AU - Kurupati, Prathiba

AU - Teng, Karen Wei Weng

AU - Gibani, Malick M.

AU - Rei, Margarida

AU - Aulicino, Anna

AU - Preciado-Llanes, Lorena

AU - Wong, Michael Thomas

AU - Becht, Etienne

AU - Howson, Lauren

AU - De Haas, Paola

AU - Salio, Mariolina

AU - Blohmke, Christoph J.

AU - Olsen, Lars Rønn

AU - Pinto, David Miguel Susano

AU - Scifo, Laura

AU - Jones, Claire

AU - Dobinson, Hazel

AU - Campbell, Danielle

AU - Juel, Helene B.

AU - Thomaides-Brears, Helena

AU - Pickard, Derek

AU - Bumann, Dirk

AU - Baker, Stephen

AU - Dougan, Gordon

AU - Simmons, Alison

AU - Gordon, Melita A.

AU - Newell, Evan William

AU - Pollard, Andrew J.

AU - Cerundolo, Vincenzo

PY - 2018/6/20

Y1 - 2018/6/20

N2 - 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.

AB - 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.

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