{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Robinson MA"],"funding":["UKRI Medical Research Council","Medical Research Council","AstraZeneca","Wellcome Trust"],"pagination":["114768"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7618755"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["43(9)"],"pubmed_abstract":["The CTLA-4 and PD-1 checkpoints control immune responses and are key targets in immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1, respectively. This cis interaction prevents PD-1-PD-L1 binding but is reversed by CTLA-4 trans-endocytosis of CD80. However, how CTLA-4 selectively removes CD80, but not PD-L1, is unclear. Here, we show CTLA-4-CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both rigidity and bivalency of CTLA-4 molecules are required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD"],"journal":["Cell reports"],"pubmed_title":["Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt the cis CD80/PD-L1 interaction."],"pmcid":["PMC7618755"],"funding_grant_id":["MR/R015759/1","227384/Z/23/Z","204798/Z/16/Z","MR/W006774/1","MR/Y001273/1"],"pubmed_authors":["Filer L","Dovedi SJ","Sansom DM","Lloyd C","Kennedy A","Yeung K","Chen HC","Waters E","Orozco CT","Robinson MA","Giovacchini D","Hinze C"],"additional_accession":[]},"is_claimable":false,"name":"Rigid, bivalent CTLA-4 binding to CD80 is required to disrupt the cis CD80/PD-L1 interaction.","description":"The CTLA-4 and PD-1 checkpoints control immune responses and are key targets in immunotherapy. Both pathways are connected via a cis interaction between CD80 and PD-L1, the ligands for CTLA-4 and PD-1, respectively. This cis interaction prevents PD-1-PD-L1 binding but is reversed by CTLA-4 trans-endocytosis of CD80. However, how CTLA-4 selectively removes CD80, but not PD-L1, is unclear. Here, we show CTLA-4-CD80 interactions are unimpeded by PD-L1 and that CTLA-4 binding with CD80 does not displace PD-L1 per se. Rather, both rigidity and bivalency of CTLA-4 molecules are required to orientate CD80 such that PD-L1 interactions are no longer permissible. Moreover, soluble CTLA-4 released PD-L1 only at specific expression levels of CD80 and PD-L1, whereas CTLA-4 trans-endocytosis released PD","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Sep","modification":"2026-07-16T06:56:18.668Z","creation":"2026-07-09T13:10:41.553Z"},"accession":"S-EPMC7618755","cross_references":{"pubmed":["39277860"],"doi":["10.1016/j.celrep.2024.114768"]}}