Simultaneously inferring T cell fate and clonality from single cell transcriptomes Event

Abstract: The heterodimeric T cell receptor (TCR) comprises two protein chains that pair to determine the antigen specificity of each T lymphocyte. The enormous sequence diversity within TCR repertoires allows specific TCR sequences to be used as lineage markers for T cells that derive from a common progenitor. We have developed a method to reconstruct full-length, paired TCR sequences from T lymphocyte single-cell RNA-seq without the need for alteration of standard RNA-seq protocols. The TCR sequences can be used to infer clonal relationships between T cells whilst the complete transcriptional landscape quantified from the remaining RNA-seq data allows determination of each cell's functional state. This provides a powerful tool to link T cell specificity with functional response in a variety of normal and pathological conditions. We have demonstrated the use of this method by determining the distribution of members of expanded T cell clonotypes in response to Salmonella infection in the mouse, where members of the same clonotype span early activated CD4+ T cells, as well as mature effector and memory cells.