T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition

• DOI: 10.1126/science.aaf1292
• Publication Date: 2017-03-10T02:05:22Z
• Authors: Enfu Hui; Jeanne Cheung; Jing Zhu; Xiaolei Su; Marcus J. Taylor; Heidi A. Wallweber; Dibyendu K. Sasmal; Jun Huang; Jeong M. Kim; Ira Mellman; Ronald D. Vale
• Keywords: Dephosphorylation

Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T activation and an important cancer immunotherapy target. Upon by its ligand PD-L1, PD-1 thought to suppress signaling through the (TCR). By titrating in biochemical reconstitution system, we demonstrate co-receptor CD28 strongly preferred over TCR as target for dephosphorylation PD-1-recruited Shp2 phosphatase. We also show CD28, but not TCR, preferentially dephosphorylated response PD-L1 intact system. These results reveal function primarily inactivating signaling, suggesting costimulatory pathways play key roles regulating effector responses anti-PD-L1/PD-1 therapy.