Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Nature Immunology |
Volume | 19 |
Issue number | 7 |
Pages (from-to) | 742-754 |
Number of pages | 13 |
ISSN | 1529-2908 |
DOIs | |
Publication status | Published - 2018 |
Externally published | Yes |
Bibliographical note
Publisher Correction: Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses (Nature Immunology, (2018), 19, 7, (742-754), 10.1038/s41590-018-0133-z)
ID: 239671572