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

Tsvetelina Pentcheva-Hoang, Lieping Chen, Andrew Mark Pardoll, James P. Allison

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)17765-17770
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number45
DOIs
StatePublished - Nov 6 2007

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Immunological Synapses
Dendritic Cells
Ligands
T-Lymphocytes
trans-Golgi Network
T-Cell Antigen Receptor
Synapses
Cell Death
Cell Membrane
Cytokines

Keywords

  • B7-DC
  • B7-H1
  • Costimulation
  • IL-4
  • LPS

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability. / Pentcheva-Hoang, Tsvetelina; Chen, Lieping; Pardoll, Andrew Mark; Allison, James P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 45, 06.11.2007, p. 17765-17770.

Research output: Contribution to journalArticle

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