Ligand mobility modulates immunological synapse formation and T cell activation.
Ligand mobility modulates immunological synapse formation and T cell activation.
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DOI：
10.1371/journal.pone.0032398
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Baumgart T
中科院分区：
文献类型：
--
作者：
Hsu CJ;Hsieh WT;Waldman A;Clarke F;Huseby ES;Burkhardt JK;Baumgart T
T cell receptor (TCR) engagement induces clustering and recruitment to the plasma membrane of many signaling molecules, including the protein tyrosine kinase zeta-chain associated protein of 70 kDa (ZAP70) and the adaptor SH2 domain-containing leukocyte protein of 76 kDa (SLP76). This molecular rearrangement results in formation of the immunological synapse (IS), a dynamic protein array that modulates T cell activation. The current study investigates the effects of apparent long-range ligand mobility on T cell signaling activity and IS formation. We formed stimulatory lipid bilayers on glass surfaces from binary lipid mixtures with varied composition, and characterized these surfaces with respect to diffusion coefficient and fluid connectivity. Stimulatory ligands coupled to these surfaces with similar density and orientation showed differences in their ability to activate T cells. On less mobile membranes, central supramolecular activation cluster (cSMAC) formation was delayed and the overall accumulation of CD3ζ at the IS was reduced. Analysis of signaling microcluster (MC) dynamics showed that ZAP70 MCs exhibited faster track velocity and longer trajectories as a function of increased ligand mobility, whereas movement of SLP76 MCs was relatively insensitive to this parameter. Actin retrograde flow was observed on all surfaces, but cell spreading and subsequent cytoskeletal contraction were more pronounced on mobile membranes. Finally, increased tyrosine phosphorylation and persistent elevation of intracellular Ca2+ were observed in cells stimulated on fluid membranes. These results point to ligand mobility as an important parameter in modulating T cell responses.
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影响因子：
3.9
作者：
Lou, Chengfei;Wang, Zifu;Wang, Szu-Wen
通讯作者：
Wang, Szu-Wen
DOI：
10.4049/jimmunol.0903071
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Carroll-Portillo A;Spendier K;Pfeiffer J;Griffiths G;Li H;Lidke KA;Oliver JM;Lidke DS;Thomas JL;Wilson BS;Timlin JA
通讯作者：
Timlin JA
影响因子：
2.9
作者：
JACOBS, R;OLDFIELD, E
通讯作者：
OLDFIELD, E
DOI：
10.1073/pnas.0902621106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Hartman, Nina C.;Nye, Jeffrey A.;Groves, Jay T.
通讯作者：
Groves, Jay T.
DOI：
10.1073/pnas.0511026103
发表时间：
2006-02-14
影响因子：
11.1
作者：
Gambin, Y;Lopez-Esparza, R;Urbach, W
通讯作者：
Urbach, W