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Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17765-70. Epub 2007 Oct 29.

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

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  • 1Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Abstract

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.

PMID:
17968013
[PubMed - indexed for MEDLINE]
PMCID:
PMC2077030
Free PMC Article
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