Continuous-Time Birth and Death Processes: Diversity Maintenance of Naïve T Cells in the Periphery

Molina-Parı́s, Carmen; Stirk, Emily R.; Quinn, Katie; Lythe, Grant

doi:10.1007/978-1-4419-7725-0_8

Cited by 2 publications

(4 citation statements)

References 12 publications

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“…4 . Consider the following quantities ( Stirk et al, 2008 , Stirk et al, 2010 , Molina-París et al, 2011 , Molina-París et al, 2011 ): The set of self pMHCs that are recognised by T cells of clonotype i is denoted by Q i , and the number of self pMHC subsets in Q i , by ϕ i . The set of T cells that recognise a self pMHC q is denoted by C q ( t ), and the number of surviving clonotypes in C q by

.…”

Section: Methodsmentioning

confidence: 99%

“…In our model, the effect of the thymus is to create new clonotypes, not to add new cells to existing clonotypes. We have previously analysed models that focus on the dynamics of one or two clonotypes without explicitly taking the multiclonal nature of the TCR repertoire into account ( Stirk et al, 2008 , Stirk et al, 2010 , Molina-París et al, 2011 , Molina-París et al, 2011 ). In this work, the variables are the integer numbers of cells of each clonotype; a death or division event changes one of the variables by one cell.…”

Section: Introductionmentioning

confidence: 99%

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How many TCR clonotypes does a body maintain?

Lythe

Callard

Hoare

et al. 2016

Journal of Theoretical Biology

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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.

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.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

How many TCR clonotypes does a body maintain?

Lythe

Callard

Hoare

et al. 2016

Journal of Theoretical Biology

Self Cite

160

156

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show abstract

“…We were interested in developing mathematical models to describe the dynamics of T cell responses to different pathogens, and T cell cross-reactivity and its roles in infection, T cell homeostasis and the establishment of T cell memory. We followed the mathematical methods and approaches developed by Stirk et al [ 56 , 57 , 58 , 59 , 60 ] and introduced a bipartite network which encodes the pMHC (or antigen) recognition pattern for each T cell clonotype, characterized by its specific TCR (see Figure 6 ). We note that the bipartite network introduced by Stirk et al considers only self-pMHC complexes.…”

Section: Modeling T Cell Cross-reactivity With a Bipartite Recognition Networkmentioning

confidence: 99%

“… Bipartite recognition network generalizing the model developed by Stirk et al [ 56 , 57 , 58 , 59 , 60 ]. Each green circle (or node) represents a T cell clonotype.…”

Section: Figurementioning

confidence: 99%

Quantifying T Cell Cross-Reactivity: Influenza and Coronaviruses

Gaevert

Duque

Lythe

et al. 2021

Viruses

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If viral strains are sufficiently similar in their immunodominant epitopes, then populations of cross-reactive T cells may be boosted by exposure to one strain and provide protection against infection by another at a later date. This type of pre-existing immunity may be important in the adaptive immune response to influenza and to coronaviruses. Patterns of recognition of epitopes by T cell clonotypes (a set of cells sharing the same T cell receptor) are represented as edges on a bipartite network. We describe different methods of constructing bipartite networks that exhibit cross-reactivity, and the dynamics of the T cell repertoire in conditions of homeostasis, infection and re-infection. Cross-reactivity may arise simply by chance, or because immunodominant epitopes of different strains are structurally similar. We introduce a circular space of epitopes, so that T cell cross-reactivity is a quantitative measure of the overlap between clonotypes that recognize similar (that is, close in epitope space) epitopes.

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Continuous-Time Birth and Death Processes: Diversity Maintenance of Naïve T Cells in the Periphery

Cited by 2 publications

References 12 publications

How many TCR clonotypes does a body maintain?

How many TCR clonotypes does a body maintain?

Quantifying T Cell Cross-Reactivity: Influenza and Coronaviruses

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