Implications of signal integration for T cell trafficking.

<p>Throughout, a hypothetical infection affecting 25% of the LNs is simulated, and the cognate DC encounter rate in LNs is . <b>(A)</b> Trajectory of a combined simulation of circulation between organs (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003752#pcbi-1003752-g004" target="_blank">Figure 4D</a>) and probabilistic priming within draining LNs (dLNs) (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003752#pcbi-1003752-g001" target="_blank">Figure 1C</a>). Because both migration and priming are stochastic, Ag-specific cells can egress unprimed from dLNs. <b>(B)</b> Illustration of the difference between the default stochastic LN transit (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003752#pcbi-1003752-g004" target="_blank">Figure 4</a>) and simulations of deterministic LN transit, where the LN transit time is fixed. <b>(C)</b> Capture times of <i>in silico</i> cells with deterministic LN transit and signal integration or probabilistic priming. The asterisk shows the “optimal” transit time for signal integration at an Ag dose with 8 required contacts, which falls in the <i>in vivo</i> range (gray area). In contrast, the optimal transit time for a 2 h phase I is shorter than typical <i>in vivo</i> estimates (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003752#pcbi-1003752-t001" target="_blank">Table 1</a>). <b>(D)</b> Capture times for stochastic LN transit with an average transit time of 11 h and standard deviation of ∼7 h compared to a fixed transit time of ∼11 h at various Ag concentrations ([Ag]). Stochastic transit is less sensitive to Ag dose variations, and has a much faster capture time for the lowest Ag concentration at 24 contacts. <b>(E)</b> Predicted benefits and risks of LN transit optimization. For various Ag doses (required contact numbers below each column), capture times of simulations with deterministic transit that would be optimal for a certain Ag dose (transit times and required contact numbers shown above column groups) were compared to the capture times of stochastic transit. Colored bars show fold differences. For example, deterministic LN transit in ∼3.7 h detects an Ag dose with 2 required contacts, for which it is optimal, almost twice as fast as stochastic transit. However, it also detects an Ag dose with 10 required contacts ∼64-fold slower.