A generic cell surface ligand system for studying cell-cell recognition.,PLOS Biology

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A generic cell surface ligand system for studying cell-cell recognition.
PLOS Biology ( IF 7.8 ) Pub Date : 2019-12-09 , DOI: 10.1371/journal.pbio.3000549
Eleanor M Denham ₁ , Michael I Barton ₁ , Susannah M Black ₁ , Marcus J Bridge ₁ , Ben de Wet ₁ , Rachel L Paterson ₁ , P Anton van der Merwe ₁ , Jesse Goyette _{1,

2}

Affiliation

Dose-response experiments are a mainstay of receptor biology studies and can reveal valuable insights into receptor function. Such studies of receptors that bind cell surface ligands are currently limited by the difficulty in manipulating the surface density of ligands at a cell-cell interface. Here, we describe a generic cell surface ligand system that allows precise manipulation of cell surface ligand densities over several orders of magnitude. These densities are robustly quantifiable, a major advance over previous studies. We validate the system for a range of immunoreceptors, including the T-cell receptor (TCR), and show that this generic ligand stimulates via the TCR at a similar surface density as its native ligand. We also extend our work to the activation of chimeric antigen receptors. This novel system allows the effect of varying the surface density, valency, dimensions, and affinity of the ligand to be investigated. It can be readily broadened to other receptor-cell surface ligand interactions and will facilitate investigation into the activation of, and signal integration between, cell surface receptors.

中文翻译：

用于研究细胞-细胞识别的通用细胞表面配体系统。

剂量反应实验是受体生物学研究的支柱，可以揭示对受体功能的宝贵见解。这种结合细胞表面配体的受体的研究目前受到在细胞 - 细胞界面处操纵配体表面密度的困难的限制。在这里，我们描述了一个通用的细胞表面配体系统，该系统允许在几个数量级上精确操纵细胞表面配体密度。这些密度是可以量化的，这是对先前研究的重大进步。我们验证了该系统的一系列免疫受体，包括 T 细胞受体 (TCR)，并表明这种通用配体通过 TCR 以与其天然配体相似的表面密度进行刺激。我们还将我们的工作扩展到嵌合抗原受体的激活。这种新系统允许改变待研究配体的表面密度、化合价、尺寸和亲和力的影响。它可以很容易地扩展到其他受体-细胞表面配体相互作用，并有助于研究细胞表面受体的激活和信号整合。

更新日期：2019-12-11

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