High-throughput and single-cell T cell receptor sequencing technologies

This Review discusses methodological advances for high-throughput analysis of the TCR repertoire at bulk and single-cell resolution. T cells express T cell receptors (TCRs) composed of somatically recombined TCR alpha and TCR beta chains, which mediate recognition of major histocompatibility complex (MHC)-antigen complexes and drive the antigen-specific adaptive immune response to pathogens and cancer. The TCR repertoire in each individual is highly diverse, which allows for recognition of a wide array of foreign antigens, but also presents a challenge in analyzing this response using conventional methods. Recent studies have developed high-throughput sequencing technologies to identify TCR sequences, analyze their antigen specificities using experimental and computational tools, and pair TCRs with transcriptional and epigenetic cell state phenotypes in single cells. In this Review, we highlight these technological advances and describe how they have been applied to discover fundamental insights into T cell-mediated immunity.

Automated summary

This Review discusses methodological advances in high-throughput analysis of the TCR repertoire, particularly at single-cell resolution. Recent studies have developed high-throughput sequencing technologies to identify TCR sequences and analyze their antigen specificities, providing important insights into T cell-mediated immune responses.