부산대학교 도서관

To tackle the complexity of cross-reactive and pathogen-specific T cell responses against related Salmonellaserovars, 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 entericaserovar Typhi (S. Typhi) or SalmonellaParatyphi A (S. Paratyphi). We describe the expansion of cross-reactive responses against distantly related Salmonellaserovars 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. Typhoidal Salmonellais a major pathogen, but there is still a lack of knowledge about suitable vaccine antigens. Cerundolo and colleagues deep-phenotype bacteria-specific CD4+T cells of Salmonella-infected volunteers to define cross-reactive and serovar-specific responses.