Department of Biology II, Ludwig-Maximilians-Universität München, Germany.
Hum Immunol. 2013 Apr;74(4):412-6. doi: 10.1016/j.humimm.2012.11.026. Epub 2012 Dec 7.
Carefully orchestrated intercellular communication is an essential prerequisite for an effective immune response. In recent years tunneling nanotubes (TNT) have emerged as a novel mechanism of cell-cell communication. These long membrane protrusions can establish cytoplasmic continuity between distant cells and enable the exchange of cellular components. In the present study we addressed the question whether these structures can facilitate the intercellular transfer of MHC class I molecules. We found a transmembrane HLA-A2-EGFP but not a soluble HLA-G1s-EGFP fusion protein to be effectively transferred between HeLa cells. Inhibition of actin polymerization significantly reduced the HLA-A2 transfer rate, indicating that transfer is dependent on tunneling nanotubes, whose de novo formation requires actin polymerization. Furthermore, overexpression of the nanotube-inducing protein LST1 promoted transfer of HLA-A2. Moreover, LST1 protein expression is enhanced in antigen presenting cells. Our results indicate that tunneling nanotubes can mediate transfer of MHC class I molecules between distant cells.
精心协调的细胞间通讯是有效免疫反应的必要前提。近年来，隧道纳米管（TNT）已成为细胞间通讯的一种新机制。这些长的膜突起可以在远距离的细胞之间建立细胞质连续性，并允许细胞成分的交换。在本研究中，我们探讨了这些结构是否可以促进 MHC Ⅰ类分子的细胞间转移。我们发现跨膜 HLA-A2-EGFP 而不是可溶性 HLA-G1s-EGFP 融合蛋白可以在 HeLa 细胞之间有效转移。肌动蛋白聚合的抑制显著降低了 HLA-A2 的转移率，表明转移依赖于隧道纳米管，其新形成需要肌动蛋白聚合。此外，诱导蛋白 LST1 的过表达促进了 HLA-A2 的转移。此外，抗原呈递细胞中 LST1 蛋白的表达增强。我们的结果表明，隧道纳米管可以介导 MHC Ⅰ类分子在远距离细胞之间的转移。
