{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Willcox CR"],"funding":["Guy’s and St Thomas’ Charity Prize","Francis Crick Institute","King’s Bioscience Institute","Cancer Research UK","The Francis Crick Institute","Medical Research Council","National Institute for Health Research (NIHR)","Wellcome Trust"],"pagination":["813-825.e4"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6868513"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["51(5)"],"pubmed_abstract":["Butyrophilin (BTN) and butyrophilin-like (BTNL/Btnl) heteromers are major regulators of human and mouse γδ T cell subsets, but considerable contention surrounds whether they represent direct γδ T cell receptor (TCR) ligands. We demonstrate that the BTNL3 IgV domain binds directly and specifically to a human Vγ4<sup>+</sup> TCR, \"LES\" with an affinity (∼15-25 μM) comparable to many αβ TCR-peptide major histocompatibility complex interactions. Mutations in germline-encoded Vγ4 CDR2 and HV4 loops, but not in somatically recombined CDR3 loops, drastically diminished binding and T cell responsiveness to BTNL3-BTNL8-expressing cells. Conversely, CDR3γ and CDR3δ loops mediated LES TCR binding to endothelial protein C receptor, a clonally restricted autoantigen, with minimal CDR1, CDR2, or HV4 con"],"journal":["Immunity"],"pubmed_title":["Butyrophilin-like 3 Directly Binds a Human Vγ4&lt;sup&gt;+&lt;/sup&gt; T Cell Receptor Using a Modality Distinct from Clonally-Restricted Antigen."],"pmcid":["PMC6868513"],"funding_grant_id":["FC001093","10093","NIHR-INF-1086","099266/Z/12/Z","208400/Z/17/Z","106292/Z/14/Z","10015"],"pubmed_authors":["Hayday AC","Willcox BE","Salim M","Melandri D","Jeeves M","Zanardo L","Zlatareva I","George R","Kjaer S","Mohammed F","Willcox CR","Vantourout P"],"additional_accession":[]},"is_claimable":false,"name":"Butyrophilin-like 3 Directly Binds a Human Vγ4&lt;sup&gt;+&lt;/sup&gt; T Cell Receptor Using a Modality Distinct from Clonally-Restricted Antigen.","description":"Butyrophilin (BTN) and butyrophilin-like (BTNL/Btnl) heteromers are major regulators of human and mouse γδ T cell subsets, but considerable contention surrounds whether they represent direct γδ T cell receptor (TCR) ligands. We demonstrate that the BTNL3 IgV domain binds directly and specifically to a human Vγ4<sup>+</sup> TCR, \"LES\" with an affinity (∼15-25 μM) comparable to many αβ TCR-peptide major histocompatibility complex interactions. Mutations in germline-encoded Vγ4 CDR2 and HV4 loops, but not in somatically recombined CDR3 loops, drastically diminished binding and T cell responsiveness to BTNL3-BTNL8-expressing cells. Conversely, CDR3γ and CDR3δ loops mediated LES TCR binding to endothelial protein C receptor, a clonally restricted autoantigen, with minimal CDR1, CDR2, or HV4 con","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Nov","modification":"2026-05-03T18:38:47.8Z","creation":"2021-02-19T19:44:02Z"},"accession":"S-EPMC6868513","cross_references":{"pubmed":["31628053"],"doi":["10.1016/j.immuni.2019.09.006"]}}