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
et al (show 20 more authors) (2018) Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses. Nature Immunology, 19. 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.

Item Type: Article
Uncontrolled Keywords: Bacterial infection, Cellular immunity
Depositing User: Symplectic Admin
Date Deposited: 12 Feb 2019 11:51
Last Modified: 13 Jan 2021 15:10
DOI: 10.1038/s41590-018-0133-z
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3032718