Rare event simulation for T-cell activation

DOI10.1007/S10955-008-9672-2zbMATH Open1162.82014arXiv0901.2227OpenAlexW2030926602MaRDI QIDQ1018052FDOQ1018052

Authors: Florian Lipsmeier, Ellen Baake 

Publication date: 13 May 2009

Published in: Journal of Statistical Physics (Search for Journal in Brave)

Abstract: The problem of emph{statistical recognition} is considered, as it arises in immunobiology, namely, the discrimination of foreign antigens against a background of the body's own molecules. The precise mechanism of this foreign-self-distinction, though one of the major tasks of the immune system, continues to be a fundamental puzzle. Recent progress has been made by van den Berg, Rand, and Burroughs (2001), who modelled the emph{probabilistic} nature of the interaction between the relevant cell types, namely, T-cells and antigen-presenting cells (APCs). Here, the stochasticity is due to the random sample of antigens present on the surface of every APC, and to the random receptor type that characterises individual T-cells. It has been shown previously that this model, though highly idealised, is capable of reproducing important aspects of the recognition phenomenon, and of explaining them on the basis of stochastic rare events. These results were obtained with the help of a refined large deviation theorem and were thus asymptotic in nature. Simulations have, so far, been restricted to the straightforward simple sampling approach, which does not allow for sample sizes large enough to address more detailed questions. Building on the available large deviation results, we develop an importance sampling technique that allows for a convenient exploration of the relevant tail events by means of simulation. With its help, we investigate the mechanism of statistical recognition in some depth. In particular, we illustrate how a foreign antigen can stand out against the self background if it is present in sufficiently many copies, although no emph{a priori} difference between self and nonself is built into the model.

Full work available at URL: https://arxiv.org/abs/0901.2227

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zbMATH Keywords

large deviationsrare event simulationstatistical recognitionimmunobiology

Mathematics Subject Classification ID

Large deviations (60F10) Biochemistry, molecular biology (92C40) Cell movement (chemotaxis, etc.) (92C17)

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Cited In (3)

• A probabilistic approach to antigen-antibody recognition
• How T-cells use large deviations to recognize foreign antigens
• Stochastic modelling of T-cell activation

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