T cell receptor diversity in the human thymus

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http://hdl.handle.net/10138/224533

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Vanhanen , R , Heikkila , N , Aggarwal , K , Hamm , D , Tarkkila , H , Pätilä , T , Jokiranta , T S , Saramaki , J & Arstila , T P 2016 , ' T cell receptor diversity in the human thymus ' , Molecular Immunology , vol. 76 , pp. 116-122 . https://doi.org/10.1016/j.molimm.2016.07.002

Title: T cell receptor diversity in the human thymus
Author: Vanhanen, Reetta; Heikkila, Nelli; Aggarwal, Kunal; Hamm, David; Tarkkila, Heikki; Pätilä, Tommi; Jokiranta, T. Sakari; Saramaki, Jari; Arstila, T. Petteri
Other contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum








Date: 2016-08
Language: eng
Number of pages: 7
Belongs to series: Molecular Immunology
ISSN: 0161-5890
DOI: https://doi.org/10.1016/j.molimm.2016.07.002
URI: http://hdl.handle.net/10138/224533
Abstract: A diverse T cell receptor (TCR) repertoire is essential for adaptive immune responses and is generated by somatic recombination of TCR alpha and TCR beta gene segments in the thymus. Previous estimates of the total TCR diversity have studied the circulating mature repertoire, identifying 1 to 3 x 10(6) unique TCR beta and 0.5 x 10(6) TCR alpha 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 x 10(6) unique TCR beta sequences and 3.7 x 10(6) TCR alpha 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 x 10(6) unique TCR beta sequences and 60 to 100 x 10(6) TCR alpha 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. (C) 2016 Elsevier Ltd. All rights reserved.
Subject: T cell
Thymus
TCR diversity
Repertoire
EXPRESSION
REPERTOIRE
SELECTION
LOCUS
3111 Biomedicine
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