Parameter estimates for the models of target cell kinetics in blood and spleen.

<p>Parameter estimates for the models of target cell kinetics in blood and spleen.</p

Three alternative models of the kinetics of peptide-pulsed and unpulsed cells in the blood and spleen.

<p>In the Decay model, peptide-pulsed targets uniformly and gradually lose susceptibility to lysis; in the Hidden-target model, only a proportion of peptide-pulsed targets are susceptible to lysis; and in the Hybrid model, peptide-pulsed targets maintain susceptibility but transition at <i>per-capita</i> rate into a non-susceptible state.</p

Schematic of model of killing of peptide-pulsed targets by specific CTL <i>in vitro</i>.

<p>CTL that have not previously engaged in lysis (LAMP⁺, green) initially form conjugates with peptide pulsed targets (purple) with mass-action kinetics at rate . These dissociate at rate or remain stable till the CTL shows signs of delivery of lytic granules (LAMP⁺. The CTL stays bound to its (presumed) apoptotic targets for mean time and then dissociates as in the LAMP⁺ state (blue).</p

The Predicted Steady-State Pool Size as a Function of Virus Infectivity p, in the Presence of Different Levels of Immune Activation <i>a*</i>

<p>The Predicted Steady-State Pool Size as a Function of Virus Infectivity p, in the Presence of Different Levels of Immune Activation <i>a*</i></p

The <i>in vivo</i> killing assay.

<p>The <i>in vivo</i> killing assay.</p

Modeling the in-vivo cytotoxicity assay.

<p><b>A</b>: Timecourses of fractional killing in the spleen, broken down by peptide dose between M and M, decreasing top to bottom) and target cell type, with 5 mice per time point (green points). Curves show the predictions of the best-fitting (hybrid) model. <b>B</b>: Key best-fit parameters governing killing of pulsed targets in the spleen, with 95% confidence intervals.</p

Influenza-specific F5 CTL are distributed heterogeneously within the spleen.

<p><b>A</b>: Imaging of the spatial distribution of F5 CTL within T and B cell areas and red pulp of spleen. <b>B</b>: Statistical comparison of F5 densities in these areas. <b>C</b>: Using <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003805#pcbi.1003805.e129" target="_blank">equation 5</a> with these data to establish the relative efficiency with which F5 CTL kill B and T cell targets after locating them.</p

Kinetics of MHC class I turnover on B and T cells.

<p>MHC class I expression was measured (MFI, arbitrary units) following blocking of its transport to the cell surface. Its decay followed approximately first-order kinetics, and occurred faster on T than on B cells.</p

Steady-State Pool Size as a Function of Virus Infectivity <i>p</i>

<p>Steady-State Pool Size as a Function of Virus Infectivity <i>p</i></p

The Predicted Time for Memory CD4⁺ T Cell Numbers to Decline from 100% to 50% of Healthy Numbers, as a Function of Virus Infectivity <i>p</i>

<p>The Predicted Time for Memory CD4⁺ T Cell Numbers to Decline from 100% to 50% of Healthy Numbers, as a Function of Virus Infectivity <i>p</i></p