Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Nature Immunology |
Vol/bind | 19 |
Udgave nummer | 7 |
Sider (fra-til) | 742-754 |
Antal sider | 13 |
ISSN | 1529-2908 |
DOI | |
Status | Udgivet - 2018 |
Eksternt udgivet | Ja |
ID: 239671572