How many TCR clonotypes does a body maintain?

Grant Lythe,Robin E Callard,Rollo L Hoare,Carmen Molina-París

doi:10.1016/j.jtbi.2015.10.016

Grant Lythe, Robin E Callard + Show 2 more

Open Access

https://doi.org/10.1016/j.jtbi.2015.10.016

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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.

Highlights

IntroductionEmerging from the thymus with a pattern of recognition of self pMHC that enabled it to survive positive and negative selection, each T cell receptors (TCR) clonotype is a species that competes for “space” or “niche” in the periphery (De Boer and Perelson, 1997; Tanchot et al, 1997; Goldrath and Bevan, 1999; Jameson, 2002; Troy and Shen, 2003; Hataye et al, 2006; Moon et al, 2007; Agenes et al, 2008; Leitao et al, 2009)
Emerging from the thymus with a pattern of recognition of self pMHC, each T cell receptors (TCR) clonotype is a species that competes in the pool of pre-established ones
We have analysed naive T cell homeostasis by considering the lifetimes of sets of cells making up TCR clonotypes, from generation in the thymus to extinction in the periphery

Summary

Introduction

Emerging from the thymus with a pattern of recognition of self pMHC that enabled it to survive positive and negative selection, each TCR clonotype is a species that competes for “space” or “niche” in the periphery (De Boer and Perelson, 1997; Tanchot et al, 1997; Goldrath and Bevan, 1999; Jameson, 2002; Troy and Shen, 2003; Hataye et al, 2006; Moon et al, 2007; Agenes et al, 2008; Leitao et al, 2009). Naive T cells in the human body have lifetimes measured in years; most naive peripheral T cells are daughter cells of other naive peripheral T cells (Vrisekoop et al, 2008; Murray et al, 2003; Houston et al, 2011)

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