Summary

The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed. Here we present TRAPeS, a publicly available tool that can efficiently extract TCR sequence information from short-read scRNA-seq libraries. We apply it to investigate heterogeneity in the CD8+ T cell response in humans and mice, and show that it is accurate and more sensitive than existing approaches. Coupling TRAPeS with transcriptome analysis of CD8+ T cells specific for a single epitope from Yellow Fever Virus (YFV), we show that the recently described 'naive-like' memory population have significantly longer CDR3 regions and greater divergence from germline sequence than do effector-memory phenotype cells. This suggests that TCR usage is associated with the differentiation state of the CD8+ T cell response to YFV.

Overall design

overall_design too long too uplode

Contributors

Shaked Afik 1, Kathleen B Yates 2, Kevin Bi 2, Samuel Darko 3, Jernej Godec 2 4 5, Ulrike Gerdemann 2, Leo Swadling 6, Daniel C Douek 3, Paul Klenerman 6 7, Eleanor J Barnes 6 7, Arlene H Sharpe 4 5, W Nicholas Haining 2 8 9, Nir Yosef 10 11 12

Contact

To be supplemented.