Scientists reveal how cosignaling receptors dually regulate T cell activation via phase separation
Previous studies have shown that upon antigen stimulation, the T cell receptor (TCR) undergoes phase separation with the kinase Lck to mediate rapid T cell activation. However, the manner in which costimulating receptors regulate this process has remained unclear.
Scientists have uncovered the intricate regulatory mechanisms of T cell activation through the study of cosignaling receptors. Previous research has shown that the T cell receptor (TCR) undergoes phase separation with the kinase Lck to mediate rapid T cell activation. However, the role of costimulatory receptor CD28 and coinhibitory receptor PD-1 in this process has remained unclear.
A recent study published in PNAS has revealed that CD28 can undergo phase separation with Lck, promoting T cell activation, while phosphorylated PD-1 inhibits CD28/Lck phase separation. This dual regulatory mechanism involves CD28 promoting T cell activation by forming signaling condensates with Lck, while PD-1 competitively binds the CD28 intracellular domain and co-condenses with it, thereby disrupting CD28/Lck condensates and inhibiting CD28 signaling.
The researchers characterized the interaction interface between CD28 and PD-1, identified key binding sites, and designed mutants to confirm these findings. These insights provide valuable guidance for the rational design and optimization of CAR-T cells, deepening our understanding of the complex cosignaling regulatory network.
Brief written by urgent.news from Phys.org's own syndicated text. Machine-written — may contain errors; check the original before relying on it.
