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

Napolitani, Giorgio and Kurupati, Prathiba and Teng, Karen Wei Weng and Gibani, Malick M. and Rei, Margarida and Aulicino, Anna and Preciado-Llanes, Lorena and Wong, Michael Thomas and Becht, Etienne and Howson, Lauren and de Haas, Paola and Salio, Mariolina and Blohmke, Christoph J. and Olsen, Lars Rønn and Pinto, David Miguel Susano and Scifo, Laura and Jones, Claire and Dobinson, Hazel and Campbell, Danielle and Juel, Helene B. and Thomaides-Brears, Helena and Pickard, Derek and Bumann, Dirk and Baker, Stephen and Dougan, Gordon and Simmons, Alison and Gordon, Melita A. and Newell, Evan William and Pollard, Andrew J. and Cerundolo, Vincenzo. (2018) Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses. Nature immunology, 19 (7). pp. 742-754.

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Official URL: https://edoc.unibas.ch/66899/

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
UniBasel Contributors:Bumann, Dirk
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Apr 2020 19:11
Deposited On:26 Apr 2020 19:11

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