基于氢氘交换质谱法和分子模拟构建的免疫检查点CD160-HVEM复合物结构模型。

Kuncewicz Katarzyna, Spodzieja Marta, Sieradzan Adam, Karczyńska Agnieszka, Dąbrowska Katarzyna, Dadlez Michał, Speiser Daniel E, Derre Laurent, Rodziewicz-Motowidło Sylwia

University of Gdansk, Faculty of Chemistry, Department of Biomedical Chemistry, Gdansk, Poland.

University of Gdansk, Faculty of Chemistry, Department of Theoretical Chemistry, Gdansk, Poland.

Oncotarget. 2019 Jan 11;10(4):536-550. doi: 10.18632/oncotarget.26570.

CD160 is a T cell coinhibitory molecule that interacts with the herpes virus entry mediator (HVEM) on antigen-presenting cells to provide an inhibitory signal to T cells. To date, the structure of CD160 and its complex with HVEM are unknown. Here, we have identified the fragments of CD160 interacting with HVEM using ELISA tests, hydrogen/deuterium studies, affinity chromatography and mass spectrometry (MS). By combining hydrogen/deuterium exchange and mass spectrometry (HDX-MS) we obtained key information about the tertiary structure of CD160, predicting the 3D structure of the CD160-HVEM complex. Our results provide insights into the molecular architecture of this complex, serving as a useful basis for designing inhibitors for future immunotherapies.

CD160是一种T细胞共抑制分子，它与抗原呈递细胞上的疱疹病毒进入介质（HVEM）相互作用，为T细胞提供抑制信号。迄今为止，CD160及其与HVEM的复合物的结构尚不清楚。在这里，我们通过酶联免疫吸附测定（ELISA）试验、氢/氘研究、亲和色谱和质谱（MS）鉴定了CD160与HVEM相互作用的片段。通过结合氢/氘交换和质谱（HDX-MS），我们获得了有关CD160三级结构的关键信息，预测了CD160-HVEM复合物的三维结构。我们的结果为该复合物的分子结构提供了见解，为未来免疫疗法设计抑制剂提供了有用的基础。