Stochastic Model of T Cell Repolarization during Target Elimination I.
Abstract
Cytotoxic T lymphocytes (T) and natural killer cells are the main cytotoxic killer cells of the human body to eliminate pathogen-infected or tumorigenic cells (i.e., target cells). Once a natural killer or T cell has identified a target cell, they form a tight contact zone, the immunological synapse (IS). One then observes a repolarization of the cell involving the rotation of the microtubule (MT) cytoskeleton and a movement of the MT organizing center (MTOC) to a position that is just underneath the plasma membrane at the center of the IS. Concomitantly, a massive relocation of organelles attached to MTs is observed, including the Golgi apparatus, lytic granules, and mitochondria. Because the mechanism of this relocation is still elusive, we devise a theoretical model for the molecular-motor-driven motion of the MT cytoskeleton confined between plasma membrane and nucleus during T cell polarization. We analyze different scenarios currently discussed in the literature, the cortical sliding and capture-shrinkage mechanisms, and compare quantitative predictions about the spatiotemporal evolution of MTOC position and MT cytoskeleton morphology with experimental observations. The model predicts the experimentally observed biphasic ...Continue Reading
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