Identifying and antagonizing the interactions between layilin and glycosylated collagens

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.