Layilin is a small type I transmembrane receptor thought to bridge extracellular ligands with the cytoskeleton through its intracellular interactions with the scaffolding protein talin. Recent bulk- and single-cell RNA sequencing experiments have repeatedly found layilin to be highly upregulated in key T cell sub-populations in multiple disease states, suggesting its importance to the adaptive immune response. Despite this prevalence, little is known about layilin’s precise role in mediating extracellular interactions or how these interactions can be modulated in disease states. Here we take advantage of layilin’s dependence on calcium ions to discover its interactions with highly glycosylated type II, IV, V, and VI collagens. Toward exploring layilin’s role in disease, we exploited the Ca²⁺ dependence in a differential phage display strategy to engineer species cross-reactive antibodies that block this interaction.

Layilin 是一种小型 I 型跨膜受体，被认为通过其与支架蛋白 talin 的细胞内相互作用将细胞外配体与细胞骨架连接起来。最近的体细胞和单细胞 RNA 测序实验一再发现，在多种疾病状态下的关键 T 细胞亚群中，莱伊林被高度上调，这表明其对适应性免疫反应的重要性。尽管存在这种普遍性，但人们对莱伊林在介导细胞外相互作用中的确切作用或如何在疾病状态下调节这些相互作用知之甚少。在这里，我们利用莱伊林对钙离子的依赖性来发现它与高度糖基化的 II、IV、V 和 VI 型胶原蛋白的相互作用。为了探索莱伊林在疾病中的作用，我们利用了 Ca ²⁺依赖于差异噬菌体展示策略来设计阻止这种相互作用的物种交叉反应性抗体。