McKeithan, T.W.: `Kinetic proofreading in T-cell receptor signal transduction', Proc. Natl. Acad. Sci. USA, 1995, 92, pp. 5042-5046.  Home/Search   Document Not in Database   Summary   Related Articles   Check

....modeling is to start with an underdetermined description and then apply high level performance criteria to constrain or optimize the space of feasible models. In our work, we apply this approach to an extended version [3, 4] of McKeithan s kinetic proofreading model for T cell signal transduction [5] (Figure 2) By specifying constraints for model parameters and imposing a performance metric on the system behavior, it is possible to estimate the parameters without making detailed observations of the system. We treat the model as a binary detector (or communication channel, as will be seen in ....

....a performance metric, and an optimization algorithm, we estimate the parameters of the molecular signal processing system. Antigen Presenting Cell Antigen and T Cell Surfaces Presenting i Cell Before T Cell Nucleus Figure 2. A biochemical network model of T cell as a detector (based on [5] and [3, 4] 2. MOLECULE DETECTION BY T CELLS There are at least 1016 epitopes (unique binding sites) among the foreign and human self peptides, thus comprising the total number of possible signals presented to a T cell (excluding variations in the MHC 1I molecules that carry them) 6] A ....

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T.W. McKeithan, "Kinetic proofreading in T-cell receptor signal transduction," Proc Natl Acad Sci USA, vol. 92, pp. 5042-6, 1995.

....over the standard constructions of Luenberger and the extended Kalman filter are also illustrated by simulations. Most of the examples worked out in this paper, as well as the simulations testing the robustness of our observers, all concern the kinetic proofreading model proposed by McKeithan in [14] for T cell receptor signal transduction (which motivated [20] The organization of this paper is as follows: ffl This section introduces the problem as well as some notations and definitions to be adopted in this work. ffl Sections 2 and 3 introduce the observers, and the main results are ....

....test robustness of our observers, we carried out some simulations to explore their responses in two cases: existence of noise in the output measurements and unknown inputs acting in the system we wish to observe. As a working example we choose x = f(x) to be the network proposed by McKeithan in [14] and took the output to be h(x) x 1 x 2 2 ; x 1 x 4 ) 0 , as in Example 2.1. The constants were taken to be: k = 0:5; k 3 = 3; k 4 = 2; fi 3 = 1. In Figure 1, the convergence of both observers for this example is shown. 0 5 10 15 20 25 30 35 40 0 2 4 6 8 10 O OL 0 5 10 15 20 25 30 35 40 9 ....

McKeithan, T.W., "Kinetic proofreading in T-cell receptor signal transduction," Proc. Natl. Acad. Sci. USA 92(1995): 5042-5046.

....k Gamma1;N CN where the subscripted k s, as well as M and T , are arbitrary positive constants; the C i s are nonnegative functions of time t, and dots indicate derivatives with respect to t. These equations arise in immunology, and describe a possible mechanism, due to McKeithan, cf. [9], that may explain the selectivity of Tcell interactions (some more details are provided below) McKeithan analyzed the equilibria of these equations, which represent steady state regimes, mostly under the simplifying assumptions that k p;i j k p and k Gamma1;i j k Gamma1 for some fixed k p and ....

....arise in chemical networks such as the Belousov Zhabotinsky reaction or Prigogine Lefever s Brusselator (for which see e.g. 1] 3. 2 Kinetic Proofreading in T Cell Signaling The equations with which we started represent the dynamics of the kinetic proofreading model proposed by McKeithan in [9] in order to describe how a chain of modifications of the T cell receptor complex, via tyrosine phosphorylation and other reactions, may give rise to both increased sensitivity and selectivity of response. Let us introduce two additional variables T (t) and M(t) which represent the concentrations ....

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McKeithan, T.W., "Kinetic proofreading in T-cell receptor signal transduction," Proc. Natl. Acad. Sci. USA 92(1995): 5042-5046.

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McKeithan, T.W.: `Kinetic proofreading in T-cell receptor signal transduction', Proc. Natl. Acad. Sci. USA, 1995, 92, pp. 5042-5046.

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McKeithan, T.W., "Kinetic proofreading in T-cell receptor signal transduction," Proc. Natl. Acad. Sci. USA 92(1995): 5042-5046.

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