Goncalves, P, Ferrarini, M, Molina-Paris, C orcid.org/0000-0001-9828-6737 et al. (5 more authors) (2017) A new mechanism shapes the naïve CD8+ T cell repertoire: the selection for full diversity. Molecular Immunology, 85. pp. 66-80. ISSN 0161-5890
Abstract
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clone sizes. Indeed with these approaches, identical TCRs may correspond to different cells expressing the same receptor, or to several amplicons from the same T cell. We here overcame this limitation by evaluating TCRB expression in individual naïve CD8+ T cells. Of the 2269 Tcrb sequences we obtained from 13 mice, 99% were unique. Mathematical analysis of this data showed that the average number of naïve peripheral CD8+ T cells expressing the same TCRB is 1.1 cell. Since TCRA co-expression studies could only increase repertoire diversity, these results reveal that the number of naïve T cells with unique TCRs approaches the number of naïve cells. Since thymocytes undergo multiple rounds of divisions after TCRB rearrangement; and 3–5% of thymocytes survive thymic selection events; the number of cells expressing the same TCRB was expected to be much higher. Thus, these results suggest a new repertoire selection mechanism, which strongly selects for full TCRB diversity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier Ltd. This is an author produced version of a paper published in Molecular Immunology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | CD8+ T cells; Mice TCR repertoires; CDR3 sequences; TCR diversity; TCR cross-reactivity |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Applied Mathematics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 13 Feb 2017 11:01 |
Last Modified: | 08 Mar 2018 01:38 |
Published Version: | https://doi.org/10.1016/j.molimm.2017.01.026 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.molimm.2017.01.026 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:112240 |