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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