Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability

T Pentcheva-Hoang, L Chen… - Proceedings of the …, 2007 - National Acad Sciences
T Pentcheva-Hoang, L Chen, DM Pardoll, JP Allison
Proceedings of the National Academy of Sciences, 2007National Acad Sciences
Despite the importance of programmed death-1 (PD-1) for T cell inhibition, little is known
about its intracellular trafficking or requirements for localization to the immunological
synapse. Here, we show that in activated T cells, PD-1 is present at the plasma membrane,
near the Golgi and in the trans-Golgi network. Unlike CD28 and CTLA-4, PD-1 accumulation
at the synapse is extensive only when T cells interact with dendritic cells (DCs) expressing
high B7-DC levels. However, B7-H1 is also critically important, especially when the DCs …
Despite the importance of programmed death-1 (PD-1) for T cell inhibition, little is known about its intracellular trafficking or requirements for localization to the immunological synapse. Here, we show that in activated T cells, PD-1 is present at the plasma membrane, near the Golgi and in the trans-Golgi network. Unlike CD28 and CTLA-4, PD-1 accumulation at the synapse is extensive only when T cells interact with dendritic cells (DCs) expressing high B7-DC levels. However, B7-H1 is also critically important, especially when the DCs have little B7-DC. Despite this preference, B7-H1−/− DCs elicit greater cytokine secretion than B7-DC−/− DCs during T cell restimulation, possibly because they also express less B7-DC. PD-1 and CD28 have similar kinetics of synaptic accumulation, suggesting that the process involves T cell receptor-triggered cytoskeletal reorganization followed by ligand binding.
National Acad Sciences