Single cell force spectroscopy of T cells recognizing a myelin-derived peptide on antigen presenting cells.

Single cell force spectroscopy of T cells recognizing a myelin-derived peptide on antigen presenting cells.
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T细胞的单细胞力光谱识别抗原呈现细胞上髓磷脂衍生的肽的单细胞力光谱。

DOI:
10.1016/j.imlet.2010.11.005
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发表时间:
2011-04-30
期刊:
影响因子:
4.4
通讯作者:
Haemmerling, Guenter J.
Haemmerling, Guenter J.
中科院分区:
医学3区
文献类型:
--
作者:
Hoffmann, Sabrina;Hosseini, Babak H.;Hecker, Markus;Louban, Ilia;Bulbuc, Nadja;Garbi, Natalio;Wabnitz, Guido H.;Samstag, Yvonne;Spatz, Joachim P.;Haemmerling, Guenter J.

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APC上的肽-MHC复合物的T细胞识别需要细胞-细胞相互作用。导致T细胞活化的分子事件已被广泛研究,但T细胞和APC之间潜在的物理结合力在很大程度上是未知的。我们使用单细胞力谱定量的T细胞和APC之间的相互作用力,提出了一个耐受性肽来自髓鞘碱性蛋白。当T细胞与负载肽的APC接触时,相互作用力随时间增加,从10秒相互作用后的约0.5nN增加到30分钟后的约15 nN。在不存在抗原的情况下,或当使用ICAM-1阴性APC时,未观察到结合力增加。相互作用力的时间发展与免疫突触形成的动力学相关,如通过使用高通量多光谱成像流式细胞术在T细胞/APC缀合物界面处的LFA-1和TCR富集所确定的。总之,这些结果表明,ICAM-1/LFA-1重新分布到接触区域是主要负责发展的强相互作用力。高的力将保持T细胞和APC紧密接触,从而为TCR和肽-MHC复合物之间的最佳相互作用提供平台。
T-cell recognition of peptide-MHC complexes on APCs requires cell-cell interactions. The molecular events leading to T-cell activation have been extensively investigated, but the underlying physical binding forces between T-cells and APCs are largely unknown. We used single cell force spectroscopy for quantitation of interaction forces between T-cells and APCs presenting a tolerogenic peptide derived from myelin basic protein. When T-cells were brought into contact with peptide-loaded APCs, interaction forces increased with time from about 0.5 nN after 10 seconds interaction to about 15 nN after 30 minutes. In the absence of antigen, or when ICAM-1-negative APC were used, no increase in binding forces was observed. The temporal development of interaction forces correlated with the kinetics of immune synapse formation, as determined by LFA-1 and TCR enrichment at the interface of T-cell/APC conjugates using high throughput multispectral imaging flow cytometry. Together, these results suggest that ICAM-1/LFA-1 redistribution to the contact area is mainly responsible for development of strong interaction forces. High forces will keep T-cells and APCs in tight contact, thereby providing a platform for optimal interaction between TCRs and peptide-MHC complexes.
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