The limiting conditional probability distribution in a stochastic model of T cell repertoire maintenance.
The limiting conditional probability distribution (LCD) has been much studied in the field of mathematical biology, particularly in the context of epidemiology and the persistence of epidemics. However, it has not yet been applied to the immune system. One of the characteristic features of the T cell repertoire is its diversity. This diversity declines in old age, whence the concepts of extinction and persistence are also relevant to the immune system. In this paper we model T cell repertoire maintenance by means of a continuous-time birth and death process on the positive integers, where the origin is an absorbing state. We show that eventual extinction is guaranteed. The late-time behaviour of the process before extinction takes place is modelled by the LCD, which we prove always exists for the process studied here. In most cases, analytic expressions for the LCD cannot be computed but the probability distribution may be approximated by means of the stationary probability distributions of two related processes. We show how these approximations are related to the LCD of the original process and use them to study the LCD in two special cases. We also make use of the large N expansion to derive a further approximation to the LCD. The accuracy of the various approximations is then analysed.
Stirk
Emily R
ER
Department of Applied Mathematics, School of Mathematics, University of Leeds, Leeds LS2 9JT, UK. emily@maths.leeds.ac.uk
Lythe
Grant
G
van den Berg
Hugo A
HA
Hurst
Gareth A D
GA
Molina-París
Carmen
C
D000465:Algorithms; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D016013:Likelihood Functions; D008390:Markov Chains; D018448:Models, Immunological; D011336:Probability; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016008:Statistical Distributions; D013269:Stochastic Processes; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D011948:Receptors, Antigen, T-Cell