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


Authors: Pentcheva-Hoang, T.; Chen, L.; Pardoll, D. M.; Allison, J. P.
Article Title: Programmed death-1 concentration at the immunological synapse is determined by ligand affinity and availability
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. © 2007 by The National Academy of Sciences of the USA.
Keywords: controlled study; unclassified drug; nonhuman; protein localization; t-lymphocytes; animals; mice; protein; apoptosis regulatory proteins; in vitro study; b-lymphocytes; receptors, antigen, t-cell; cell membrane; ligands; fluorescence microscopy; genes, reporter; antigens, cd; antigen-presenting cells; synapse; costimulation; il-4; programmed death 1; receptors, transferrin; golgi apparatus; b7-dc; b7-h1; lps; protein programmed death 1
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 104
Issue: 45
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2007-11-06
Start Page: 17765
End Page: 17770
Language: English
DOI: 10.1073/pnas.0708767104
PUBMED: 17968013
PROVIDER: scopus
PMCID: PMC2077030
DOI/URL:
Notes: --- - "Cited By (since 1996): 19" - "Export Date: 17 November 2011" - "CODEN: PNASA" - "Source: Scopus"
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  1. James P Allison
    130 Allison
  2. Tsvetelina Pencheva Hoang
    2 Hoang