Single-cell sequencing reveals αβ chain pairing shapes the T cell repertoire

A diverse T cell repertoire is a critical component of the adaptive immune system, providing protection against invading pathogens and neoplastic changes through the recognition of foreign peptides by T cell receptors (TCRs). However, the statistical properties and function of the T cell pool in an individual, under normal physiological conditions, remain poorly understood. In this study, we comprehensively and quantitatively characterize the TCR repertoire by leveraging recent biotechnological developments in deep RNA sequencing of lymphocytes via single-cell barcoding in emulsion to obtain over 200,000 high quality paired αβ TCR sequences from 5 healthy human subjects. We use this unprecedented dataset to demonstrate non-random associations and non-monogamous pairing between the α and β chains, which functionally serves to lower the theoretical diversity of the TCR repertoire and increase the frequency of public clones shared among individuals. We additionally show that paired T cell clone sizes follow a power law distribution that is distinct from that found for either of the single chain repertoires, as well as markedly longer tails for the CD8+ cytotoxic T cells than CD4+ helper T cells. Furthermore, we report clonality estimates for the paired chain repertoire that are significantly lower than those estimated from single chain data. Taken together, these results highlight the importance of sequencing αβ pairs in accurately quantifying T-cell receptor diversity.