T cell receptor diversity in the human thymus

• Published in: Molecular immunology Vol. 76; pp. 116 - 122
• Main Authors: Vanhanen, Reetta, Heikkilä, Nelli, Aggarwal, Kunal, Hamm, David, Tarkkila, Heikki, Pätilä, Tommi, Jokiranta, T. Sakari, Saramäki, Jari, Arstila, T. Petteri
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-08-2016
• Subjects: Female; Flow Cytometry; Gene Expression Profiling - methods; High-Throughput Nucleotide Sequencing; Humans; Infant; Infant, Newborn; Male; Polymerase Chain Reaction; Receptors, Antigen, T-Cell, alpha-beta - genetics; Repertoire; T cell; TCR diversity; Thymus; Thymus Gland - immunology; Transcriptome; TCR; T cell; Repertoire; TCR diversity; DP; SP; CDR3; Thymus
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2016.07.002

•The data provides the first measurement of the human thymic T cell receptor diversity.•High-throughput sequencing of the human thymus produced 10×106 unique TCR β and 4×106 α sequences.•The result is the highest directly observed diversity so far for either chain.•Computational estimators provided an estimate of a thymic repertoire consisting of 40 to 70×106 unique TCRβ and 60 to 100×106 TCRα sequences.
A diverse T cell receptor (TCR) repertoire is essential for adaptive immune responses and is generated by somatic recombination of TCRα and TCRβ gene segments in the thymus. Previous estimates of the total TCR diversity have studied the circulating mature repertoire, identifying 1 to 3×106 unique TCRβ and 0.5×106 TCRα sequences. Here we provide the first estimate of the total TCR diversity generated in the human thymus, an organ which in principle can be sampled in its entirety. High-throughput sequencing of samples from four pediatric donors detected up to 10.3×106 unique TCRβ sequences and 3.7×106 TCRα sequences, the highest directly observed diversity so far for either chain. To obtain an estimate of the total diversity we then used three different estimators, preseq and DivE, which measure the saturation of rarefaction curves, and Chao2, which measures the size of the overlap between samples. Our results provide an estimate of a thymic repertoire consisting of 40 to 70×106 unique TCRβ sequences and 60 to 100×106 TCRα sequences. The thymic repertoire is thus extremely diverse. Moreover, extrapolation of the data and comparison with earlier estimates of peripheral diversity also suggest that the thymic repertoire is transient, with different clones produced at different times.