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.
authors.affiliation: Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Tsvetelina
authors.initials: T
authors.lastname: Pentcheva-Hoang
authors.forename: Lieping
authors.initials: L
authors.lastname: Chen
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology; D017930:Genes, Reporter; D006056:Golgi Apparatus / Q000276:immunology; D006801:Humans; D008024:Ligands; D051379:Mice; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011948:Receptors, Antigen, T-Cell; D011990:Receptors, Transferrin