1. Stochastic competitive exclusion in the maintenance of the naïve T cell repertoire
- Author
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Stirk, Emily R., Lythe, Grant, van den Berg, Hugo A., and Molina-París, Carmen
- Subjects
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STOCHASTIC analysis , *COMPETITIVE exclusion (Microbiology) , *T cells , *IMMUNE system , *ANTIGENS , *MARKOV processes , *DISTRIBUTION (Probability theory) , *COMPETITION (Biology) - Abstract
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 self-antigens 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 self-antigens they recognise. We formulate a bivariate continuous-time 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 self-antigens 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 non-extinction of both clonotypes. Finally, we derive deterministic equations for the number of cells belonging to each clonotype as well as a linear Fokker–Planck equation for the fluctuations about the deterministic stable steady state. [Copyright &y& Elsevier]
- Published
- 2010
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