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- Pattu, Varsha, et al.
(author)
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SNARE protein expression and localization in human cytotoxic T lymphocytes.
- 2012
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 42:2
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Journal article (peer-reviewed)abstract
- The major function of cytotoxic T lymphocytes (CTLs) is to eliminate pathogen-infected and tumorigenic cells. This is mediated mainly through the exocytosis of lytic granules (LGs) containing cytotoxic components, such as perforin and granzymes at the immunological synapse (IS). The soluble NSF attachment receptor (SNARE) protein isoforms are well known to be required for vesicle exocytosis in neuronal synapses, but their potential function in CTLs is only partly understood. Here, we examined the expression of SNARE proteins before and after the activation of primary human CD8(+) T cells and determined their co-localization with LGs and CD3 after IS formation with target cells. We found that several key SNARE proteins in neuronal cells were not expressed in CTLs, such as syntaxin1B2 and SNAP-25. Vti1b, Stx8 and Stx16 had the highest degrees of co-localization with LGs while Stx3, Stx4, Stx6, Stx7, Stx8, Stx13, Vti1b, VAMP3 and VAMP4 co-localized with CD3. Our data provide the first complete expression profile and localization of SNAREs in primary human CD8(+) T cells, laying the groundwork for further understanding their potential role in T-cell function.
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- Qu, Bin, et al.
(author)
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Docking of lytic granules at the immunological synapse in human CTL requires Vti1b-dependent pairing with CD3 endosomes.
- 2011
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 186:12
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Journal article (peer-reviewed)abstract
- Lytic granule (LG)-mediated apoptosis is the main mechanism by which CTL kill virus-infected and tumorigenic target cells. CTL form a tight junction with the target cells, which is called the immunological synapse (IS). To avoid unwanted killing of neighboring cells, exocytosis of lytic granules (LG) is tightly controlled and restricted to the IS. In this study, we show that in activated human primary CD8(+) T cells, docking of LG at the IS requires tethering LG with CD3-containing endosomes (CD3-endo). Combining total internal reflection fluorescence microscopy and fast deconvolution microscopy (both in living cells) with confocal microscopy (in fixed cells), we found that LG and CD3-endo tether and are cotransported to the IS. Paired but not single LG are accumulated at the IS. The dwell time of LG at the IS is substantially enhanced by tethering with CD3-endo, resulting in a preferential release of paired LG over single LG. The SNARE protein Vti1b is required for tethering of LG and CD3-endo. Downregulation of Vti1b reduces tethering of LG with CD3-endo. This leads to an impaired accumulation and docking of LG at the IS and a reduction of target cell killing. Therefore, Vti1b-dependent tethering of LG and CD3-endo determines accumulation, docking, and efficient lytic granule secretion at the IS.
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- Schreurs, G., et al.
(author)
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Analogue benchmarks of shortening and extension experiments
- 2006. - 253
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In: <em> </em>Analogue and Numerical Modeling of Crustal-Scale Processes. - : Geological Society of London. - 1862391912 ; , s. 1-27
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Book chapter (peer-reviewed)abstract
- We report a direct comparison of scaled analogue experiments to test thereproducibility of model results among ten different experimental modelling laboratories.We present results for two experiments: a brittle thrust wedge experiment and a brittleviscousextension experiment. The experimental set-up, the model construction technique,the viscous material and the base and wall properties were prescribed. However, each laboratoryused its own frictional analogue material and experimental apparatus. Comparisonof results for the shortening experiment highlights large differences in model evolutionthat may have resulted from (1) differences in boundary conditions (indenter or basal-pullmodels), (2) differences in model widths, (3) location of observation (for example, sidewallversus centre of model), (4) material properties, (5) base and sidewall frictional properties,and (6) differences in set-up technique of individual experimenters. Six laboratories carriedout the shortening experiment with a mobile wall. The overall evolution of their models isbroadly similar, with the development of a thrust wedge characterized by forward thrustpropagation and by back thrusting. However, significant variations are observed inspacing between thrusts, their dip angles, number of forward thrusts and back thrusts, andsurface slopes. The structural evolution of the brittle-viscous extension experiments issimilar to a high degree. Faulting initiates in the brittle layers above the viscous layer in close vicinity to the basal velocity discontinuity. Measurements of fault dip angles and faultspacing vary among laboratories. Comparison of experimental results indicates an encouragingoverall agreement in model evolution, but also highlights important variations in thegeometry and evolution of the resulting structures that may be induced by differences inmodelling materials, model dimensions, experimental set-ups and observation location
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