Lythe, GD orcid.org/0000-0001-7966-5571, Callard, RE, Hoare, RL et al. (1 more author) (2016) How many TCR clonotypes does a body maintain? Journal of Theoretical Biology, 389. pp. 214-224. ISSN 0022-5193
Abstract
We consider the lifetime of a T cell clonotype, the set of T cells with the same T cell receptor, from its thymic origin to its extinction in a multiclonal repertoire. Using published estimates of total cell numbers and thymic production rates, we calculate the mean number of cells per TCR clonotype, and the total number of clonotypes, in mice and humans. When there is little peripheral division, as in a mouse, the number of cells per clonotype is small and governed by the number of cells with identical TCR that exit the thymus. In humans, peripheral division is
important and a clonotype may survive for decades, during which it expands to comprise many cells. We therefore devise and analyse a computational model of homeostasis of a multiclonal population. Each T cell in the model competes for self-pMHC stimuli, cells of any one clonotype only recognising a small fraction of the many subsets of
stimuli. A constant mean total number of cells is maintained by a balance between cell division and death, and a stable number of clonotypes by a balance between thymic production of new clonotypes and extinction of existing ones. The number of distinct clonotypes in a human body may be smaller than the total number of naive T cells by only one order of magnitude.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | T cells, clonal repertoire, homeostasis, competition, extinction, stochastic modelling. |
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: | 16 Nov 2015 14:32 |
Last Modified: | 03 Mar 2020 16:59 |
Published Version: | http://dx.doi.org/10.1016/j.jtbi.2015.10.016 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jtbi.2015.10.016 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:91461 |