T Cell Activation: Cosignaling Receptors Control Phase Separation

A new study reveals how cosignaling receptors dually regulate T cell activation through phase separation. Researchers found that upon antigen stimulation, the T cell receptor (TCR) and kinase Lck form liquid-like condensates, but costimulatory receptors such as CD28 and inhibitory receptors like PD-1 can modulate this process. CD28 promotes phase separation and enhances signaling, while PD-1 disrupts condensate formation, dampening activation. This dual regulation is critical for immune responses and has implications for cancer immunotherapy and autoimmune disease treatment. Understanding these mechanisms could lead to more precise therapeutic interventions targeting T cell function.