Human thymic T cell repertoire is imprinted with strong convergence to shared sequences

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Heikkilä , N , Vanhanen , R , Yohannes , D A , Kleino , I , Mattila , I P , Saramäki , J & Arstila , T P 2020 , ' Human thymic T cell repertoire is imprinted with strong convergence to shared sequences ' , Molecular Immunology , vol. 127 , pp. 112-123 .

Title: Human thymic T cell repertoire is imprinted with strong convergence to shared sequences
Author: Heikkilä, Nelli; Vanhanen, Reetta; Yohannes, Dawit A.; Kleino, Iivari; Mattila, Ilkka P.; Saramäki, Jari; Arstila, T. Petteri
Contributor organization: Department of Bacteriology and Immunology
TRIMM - Translational Immunology Research Program
Research Programs Unit
University of Helsinki
Faculty of Medicine
Department of Medical and Clinical Genetics
HUS Children and Adolescents
Lastenkirurgian yksikkö
Children's Hospital
Helsinki University Hospital Area
Petteri Arstila / Principal Investigator
Date: 2020-11
Language: eng
Number of pages: 12
Belongs to series: Molecular Immunology
ISSN: 0161-5890
Abstract: A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCR alpha and TCR beta locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRa nucleotide repertoire was more diverse than TCR beta, with 4.1 x 10(6) vs. 0.81 x 10(6) unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRa than in TCR beta repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCR alpha and TCR beta loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCR alpha than TCR beta repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.
Subject: T cell antigen receptor
TCR repertoire
TCR recombination
next-generation sequencing
3111 Biomedicine
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion

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