| http://purl.uniprot.org/citations/28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28270509 | http://www.w3.org/2000/01/rdf-schema#comment | "Programmed cell death-1 (PD-1) is an inhibitory receptor with an essential role in maintaining peripheral tolerance and is among the most promising immunotherapeutic targets for treating cancer, autoimmunity, and infectious diseases. A complete understanding of the consequences of PD-1 engagement by its ligands, PD-L1 and PD-L2, and of PD-L1 binding to B7-1 requires quantitative analysis of their interactions at the cell surface. We present here the first complete in situ kinetic analysis of the PD-1/PD-ligands/B7-1 system. Consistent with previous solution measurements, we observed higher in situ affinities for human (h) than murine (m) PD-1 interactions, stronger binding of hPD-1 to hPD-L2 than hPD-L1, and comparable binding of mPD-1 to both ligands. However, in contrast to the relatively weak solution affinities, the in situ affinities of PD-1 are as high as those of the T cell receptor for agonist pMHC and of LFA-1 (lymphocyte function-associated antigen 1) for ICAM-1 (intercellular adhesion molecule 1) but significantly lower than that of the B7-1/CTLA-4 interaction, suggesting a distinct basis for PD-1-versus CTLA-4-mediated inhibition. Notably, the in situ interactions of PD-1 are much stronger than that of B7-1 with PD-L1. Overall, the in situ affinity ranking greatly depends on the on-rate instead of the off-rate. In silico simulations predict that PD-1/PD-L1 interactions dominate at interfaces between activated T cells and mature dendritic cells and that these interactions will be highly sensitive to the dynamics of PD-L1 and PD-L2 expression. Our results provide a kinetic framework for better understanding inhibitory PD-1 activity in health and disease."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m116.763888"xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/author | "Cheng X."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/author | "Li K."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/author | "Zhu C."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/author | "Davis S.J."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/author | "Tilevik A."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/pages | "6799-6809"xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/title | "In situ and in silico kinetic analyses of programmed cell death-1 (PD-1) receptor, programmed cell death ligands, and B7-1 protein interaction network."xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://purl.uniprot.org/core/volume | "292"xsd:string |
| http://purl.uniprot.org/citations/28270509 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28270509 |
| http://purl.uniprot.org/citations/28270509 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/28270509 |
| http://purl.uniprot.org/uniprot/#_A0A0M3M0G7-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_A0N0P2-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q02242-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_P33681-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q86TL7-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q00609-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q15116-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q544F3-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q549R2-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |
| http://purl.uniprot.org/uniprot/#_Q3U4B5-mappedCitation-28270509 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28270509 |