Quantitative analysis of the role of receptor recycling in T cell polarization.
Activation of T cells of the immune system involves recognition of the antigen by the T cell receptor and subsequent internalization and recycling of this receptor. We present a numerical model for this process that accounts for the polarity of the intracellular traffic determined by the polarization of the microtubule-organizing center to the immunological synapse. Unexpectedly, the model explains the observed accumulation of receptors at the immunological synapse mainly as dynamic maintenance of the receptor density there, while the surface receptors everywhere else are depleted, even though the internalization occurs primarily at the synapse. In the case of an unsuccessful polarization of the microtubule-organizing center, which alters the polarity of the receptor trafficking, the model explains the absence of receptor accumulation as a dynamic downregulation at the synapse. The experiment shows that in this case the interaction of the T cell with its target is aborted. Disruption of recycling leads in the experiment to accumulation of the incompletely polarized cells. We propose that receptor recycling is a mechanism whereby the cell can sense its internal structure and detect polarity errors, analogous to checkpoint signaling mechanisms that ensure fidelity of cell division.
Arkhipov
Sergey N
SN
Department of Computational Biology, University of Pittsburgh School of Medicine, Pittsburg, PA 15260, USA.
Maly
Ivan V
IV
D000465:Algorithms; D001703:Biophysics / Q000379:methods*; D020126:Brefeldin A / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D015233:Models, Statistical; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013499:Surface Properties; D013569:Synapses / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell; D020126:Brefeldin A