Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands
Theres Oakes
Division of Infection and Immunity, University College London, London, United Kingdom
Bram Gerritsen
Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, Netherlands; Department of Pathology, Yale School of Medicine, New Haven, United States
Mazlina Ismail
Division of Infection and Immunity, University College London, London, United Kingdom
James M Heather
Division of Infection and Immunity, University College London, London, United Kingdom
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.
