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Stochastic competitive exclusion in the maintenance of the naïve T cell repertoire
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Stirk, Emily R., Lythe, Grant, Berg, Hugo van den, 1968 and MolinaParis, Carmen. (2010) Stochastic competitive exclusion in the maintenance of the naïve T cell repertoire. Journal of Theoretical Biology, Vol.265 (No.3). pp. 396410. ISSN 00225193

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Official URL: http://dx.doi.org/10.1016/j.jtbi.2010.05.004
Abstract
Recognition of antigens by the adaptive immune system relies on a highly diverse T cell receptor repertoire. The mechanism that maintains this diversity is based on competition for survival stimuli; these stimuli depend upon weak recognition of selfantigens by the T cell antigen receptor. We study the dynamics of diversity maintenance as a stochastic competition process between a pair of T cell clonotypes that are similar in terms of the selfantigens they recognise. We formulate a bivariate continuoustime Markov process for the numbers of T cells belonging to the two clonotypes. We prove that the ultimate fate of both clonotypes is extinction and provide a bound on mean extinction times. We focus on the case where the two clonotypes exhibit negligible competition with other T cell clonotypes in the repertoire, since this case provides an upper bound on the mean extinction times. As the two clonotypes become more similar in terms of the selfantigens they recognise, one clonotype quickly becomes extinct in a process resembling classical competitive exclusion. We study the limiting probability distribution for the bivariate process, conditioned on nonextinction of both clonotypes. Finally, we derive deterministic equations for the number of cells belonging to each clonotype as well as a linear FokkerPlanck equation for the fluctuations about the deterministic stable steady state.
Item Type:  Journal Article 

Subjects:  Q Science > QR Microbiology 
Divisions:  Faculty of Science > Mathematics Faculty of Science > Centre for Systems Biology 
Library of Congress Subject Headings (LCSH):  T cells  Receptors  Mathematical models 
Journal or Publication Title:  Journal of Theoretical Biology 
Publisher:  Elsevier 
ISSN:  00225193 
Date:  7 August 2010 
Volume:  Vol.265 
Number:  No.3 
Number of Pages:  15 
Page Range:  pp. 396410 
Identification Number:  10.1016/j.jtbi.2010.05.004 
Status:  Peer Reviewed 
Publication Status:  Published 
Access rights to Published version:  Restricted or Subscription Access 
Funder:  Engineering and Physical Sciences Research Council (EPSRC), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) 
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URI:  http://wrap.warwick.ac.uk/id/eprint/5456 
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