TY - JOUR
T1 - Clonal analysis of Salmonella-specific effector T cells reveals serovar-specific and cross-reactive T cell responses
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.
KW - bacterial infection
KW - cellular immunity
UR - http://www.scopus.com/inward/record.url?scp=85048729839&partnerID=8YFLogxK
U2 - 10.1038/s41590-018-0133-z
DO - 10.1038/s41590-018-0133-z
M3 - Article
AN - SCOPUS:85048729839
SN - 1529-2908
VL - 19
SP - 742
EP - 754
JO - Nature Immunology
JF - Nature Immunology
IS - 7
ER -
