Models containing Itk dimers and dueling feedbacks also show higher robustness for polyclonal T cells stimulated by anti-CD3 antibodies.

Abstract

<p>PLCγ1 phosphorylation kinetics in <i>MHC<sup>−/−</sup></i> T cells stimulated by antibodies against (A) CD3 or (B) CD3 and CD4 at 1 µg/ml versus 5 µg/ml. (C) Variation of D<sub>KL</sub> with R for the <i>in silico models</i> M1–M3 (blue, red and black, respectively), M7 (yellow), and M5–M6 (purple and maroon, respectively) at initial Itk (Itk<sup>0</sup> = 100 molecules) and PIP<sub>3</sub> concentrations (PIP<sub>3</sub><sup>0</sup> = 370 molecules) at <i>τ</i><sub>p</sub> = 1 min and <i>A</i><sub>avg</sub> = 60 molecules, representing anti-CD3 stimulation at 5 µg/ml. The orange bar indicates R<i><sup>expt</sup></i>. Note we use <i>A</i><sub>avg</sub> to represent the amplitude A<sup>expt</sup> in experiments measuring fold change in Itk phosphorylation (see the main text for further details). (D) Variation of D<sub>KL</sub> with R for anti-CD3/CD4 stimulation at 5 µg/ml at <i>τ</i><sub>p</sub> = 1 min and <i>A</i><sub>avg</sub> = 80 molecules. The initial Itk (Itk<sup>0</sup> = 140 molecules) and PIP<sub>3</sub> concentrations (PIP<sub>3</sub><sup>0</sup> = 530 molecules) were used. The orange bar indicates R<i><sup>expt</sup></i>. (E) and (F) show maps of the most robust models (with the lowest D<sub>KL</sub>) as R<i><sup>expt</sup></i> and <i>A</i> (shown as <i>A</i><sub>avg</sub>) are varied for the same parameters as in (C) and (D), respectively.</p

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