TY - JOUR
T1 - Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability
AU - Pentcheva-Hoang, Tsvetelina
AU - Chen, Lieping
AU - Pardoll, Drew M.
AU - Allison, James P.
PY - 2007/11/6
Y1 - 2007/11/6
N2 - 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.
AB - 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.
KW - B7-DC
KW - B7-H1
KW - Costimulation
KW - IL-4
KW - LPS
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U2 - 10.1073/pnas.0708767104
DO - 10.1073/pnas.0708767104
M3 - Article
C2 - 17968013
AN - SCOPUS:36749010774
SN - 0027-8424
VL - 104
SP - 17765
EP - 17770
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
ER -