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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2007-7-23
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pubmed:abstractText |
The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are expressed on various somatic cells and certain cancers. Accumulating evidence suggests that interfering with the PD-1-PD-L1 interaction may result in the restoration of defective T cell functions in cancer and chronic viral infection. Herein, we established procedures to produce large amounts of renatured recombinant extracellular domain proteins of mouse PD-1 (mPD-1) and PD-L1. While monomeric mPD-1 and mouse PD-L1 (mPD-L1) only marginally interacted with the cells expressing their counterpart proteins, their tetramerization markedly enhanced the affinity with the K(d) of mPD-L1 tetramer being nearly 100-fold lower than that of the corresponding monomer. The affinity of mPD-L1 tetramer was even higher than a high-affinity anti-PD-1 mAb, and it efficiently inhibited the binding of mPD-L1/Fc-chimeric protein to mPD-1(+) cells. Functionally, mPD-L1 tetramer significantly enhanced the proliferative responses as well as the cytotoxic activity of T cells against specific target cells in vitro. The results suggest that oligomeric PD-L1 extracellular domains may provide a potential means to restore T cell functions in cancer and viral infection in humans.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cd274 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/PDCD1LG2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pdcd1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pdcd1lg2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Ligand 2...,
http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0953-8178
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pubmed:author |
pubmed-author:GarbocziDavid NDN,
pubmed-author:HayashiTamonT,
pubmed-author:HonjoTasukuT,
pubmed-author:MikamiBunzoB,
pubmed-author:MinatoNagahiroN,
pubmed-author:MuroiKaoriK,
pubmed-author:NagakuraTomokazuT,
pubmed-author:OkazakiTakuT,
pubmed-author:ShibayamaShiroS,
pubmed-author:TanakaYoshimasaY,
pubmed-author:TerawakiSeigoS
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pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
881-90
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17606978-Animals,
pubmed-meshheading:17606978-Antigens, CD274,
pubmed-meshheading:17606978-Antigens, CD80,
pubmed-meshheading:17606978-Antigens, Surface,
pubmed-meshheading:17606978-Apoptosis Regulatory Proteins,
pubmed-meshheading:17606978-Cell Line,
pubmed-meshheading:17606978-Cells, Cultured,
pubmed-meshheading:17606978-Lymphocyte Activation,
pubmed-meshheading:17606978-Membrane Glycoproteins,
pubmed-meshheading:17606978-Mice,
pubmed-meshheading:17606978-Peptides,
pubmed-meshheading:17606978-Programmed Cell Death 1 Ligand 2 Protein,
pubmed-meshheading:17606978-Programmed Cell Death 1 Receptor,
pubmed-meshheading:17606978-Protein Binding,
pubmed-meshheading:17606978-Protein Structure, Tertiary,
pubmed-meshheading:17606978-Recombinant Proteins,
pubmed-meshheading:17606978-Spleen,
pubmed-meshheading:17606978-T-Lymphocytes
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pubmed:year |
2007
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pubmed:articleTitle |
Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function.
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pubmed:affiliation |
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-Ku, Kyoto 606-8501, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Intramural
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