title: T cell receptor diversity in the human thymus.
abstract: 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 3×10(6) unique TCRβ and 0.5×10(6) 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 10.3×10(6) unique TCRβ sequences and 3.7×10(6) 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 70×10(6) unique TCRβ sequences and 60 to 100×10(6) 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.
authors.affiliation: Medicum, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, 00014 Helsinki, Finland. Electronic address: reetta.vanhanen@helsinki.fi.
authors.forename: Reetta
authors.initials: R
authors.lastname: Vanhanen
authors.affiliation: Medicum, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Nelli
authors.initials: N
authors.lastname: Heikkilä
authors.affiliation: Department of Computer Science, Aalto University, FI-00076 Aalto, Espoo, Finland.
authors.forename: Kunal
authors.initials: K
authors.lastname: Aggarwal
authors.affiliation: Adaptive Biotechnologies, 1551 Eastlake Ave. E, Seattle, WA, United States.
authors.forename: David
authors.initials: D
authors.lastname: Hamm
authors.affiliation: Medicum, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tarkkila
authors.affiliation: Department of Pediatric Cardiac and Transplantation Surgery, Hospital for Children and Adolescents, Helsinki University Central Hospital, 00290 Helsinki, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Pätilä
authors.affiliation: Medicum, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: T Sakari
authors.initials: TS
authors.lastname: Jokiranta
authors.affiliation: Department of Computer Science, Aalto University, FI-00076 Aalto, Espoo, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Saramäki
authors.affiliation: Medicum, Department of Bacteriology and Immunology and Research Programs Unit, Immunobiology, University of Helsinki, 00014 Helsinki, Finland.
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013950:Thymus Gland / Q000276:immunology*; D059467:Transcriptome
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: Repertoire; T cell; TCR diversity; Thymus