The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes

Abstract

The clone size distribution of the human naive T-cell receptor (TCR) repertoire is an important determinant of adaptive immunity. We estimated the abundance of TCR sequences in samples of naive T cells from blood using an accurate quantitative sequencing protocol. We observe most TCR sequences only once, consistent with the enormous diversity of the repertoire. However, a substantial number of sequences were observed multiple times. We detect abundant TCR sequences even after exclusion of methodological confounders such as sort contamination, and multiple mRNA sampling from the same cell. By combining experimental data with predictions from models we describe two mechanisms contributing to TCR sequence abundance. TCRα abundant sequences can be primarily attributed to many identical recombination events in different cells, while abundant TCRβ sequences are primarily derived from large clones, which make up a small percentage of the naive repertoire, and could be established early in the development of the T-cell repertoire.