Stochastic model of T Cell repolarization during target elimination (II)

  title={Stochastic model of T Cell repolarization during target elimination (II)},
  author={Ivan Horň{\'a}k and Heiko Rieger},
Cytotoxic T lymphocytes (T cells) and natural killer cells form a tight contact, the immunological synapse (IS), with target cells, where they release their lytic granules containing perforin/granzyme and cytokine containing vesicles. During this process the cell repolarizes and moves the microtubule organizing center (MTOC) towards the IS. In the first part of our work we developed a computational model for the molecular-motor-driven motion of the MT cytoskeleton during T cell polarization and… 


Stochastic model of T Cell repolarization during target elimination (I)
A theoretical model for the molecular motor driven motion of the MT half-spindle confined between plasma membrane and nucleus during T cell polarization is devised and it turns out that the localization of dyneins in the pSMAC facilitates their interaction with the MTs.
MTOC translocation modulates IS formation and controls sustained T cell signaling
Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling.
Deterministic Mechanical Model of T-Killer Cell Polarization Reproduces the Wandering of Aim between Simultaneously Engaged Targets
A three-dimensional, numerical biomechanical model of the molecular-motor-driven microtubule cytoskeleton that positions the killing apparatus demonstrates that the cortical pulling mechanism is indeed capable of orienting the killing machine into the functional position under a range of conditions and predicts experimentally testable limitations of this commonly hypothesized mechanism of T-cell polarization.
Actin clearance promotes polarized dynein accumulation at the immunological synapse
The results revealed a remarkable spatiotemporal correlation between dynein recruitment to the synaptic membrane and the depletion of cortical filamentous actin (F-actin) from the same region, suggesting that the two events were causally related.
Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells
It is proposed that the CTL plasma membrane proximal to the MTOC is particularly active in forming stable intercellular contacts, resulting in CTL-TC conjugation, and that subsequent modulation of the microtubular system of the C TL may be related to the cytolytic response and to detachment of the effector cell.
Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells.
Findings indicate that the repositioning of the MTOC and the GA, which is shared by CTL and natural killer cells, is an essential and early event in the onset of the cytolytic mechanism.
Dynamic microtubules regulate cellular contractility during T-cell activation
It is reported that traction forces generated by T cells are regulated by dynamic microtubules (MTs) at the interface, which suppress Rho activation, nonmuscle myosin II bipolar filament assembly, and actin retrograde flow at the T-cell–substrate interface.
Recruitment of dynein to the Jurkat immunological synapse
A mechanism that links signaling through the T cell receptor to translocation of the MTOC is suggested, in which the minus end-directed motor cytoplasmic dynein, localized at the synapse through an interaction with ADAP, reels in theMTOC, allowing for directed secretion along the polarized microtubule cytoskeleton.
Cytoskeleton rotation relocates mitochondria to the immunological synapse and increases calcium signals.
It is concluded that rotation-driven relocation of the MTOC towards the IS together with an accumulation of PMCA pumps at the IS are sufficient to control the observed Ca2+ dynamics in T-cells during polarization.
Dynein-driven transport of T cell receptor microclusters regulates immune synapse formation and T cell activation.
It is demonstrated that the dynein motor complex colocalized and coimmunoprecipitated with the TCR complex and that TCR-MCs moved along microtubules (MTs) toward the center of the immune synapse in a dyne in-dependent manner to form cSMAC.