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killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005, and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.","bibjson":{"author":[{"initials":"PM","lastname":"Saunders","name":"Saunders PM"},{"initials":"P","lastname":"Pymm","name":"Pymm P"},{"initials":"G","lastname":"Pietra","name":"Pietra G"},{"initials":"VA","lastname":"Hughes","name":"Hughes VA"},{"initials":"C","lastname":"Hitchen","name":"Hitchen C"},{"initials":"GM","lastname":"O'Connor","name":"O'Connor GM"},{"initials":"F","lastname":"Loiacono","name":"Loiacono F"},{"initials":"J","lastname":"Widjaja","name":"Widjaja J"},{"initials":"DA","lastname":"Price","name":"Price DA"},{"initials":"M","lastname":"Falco","name":"Falco M"},{"initials":"MC","lastname":"Mingari","name":"Mingari MC"},{"initials":"L","lastname":"Moretta","name":"Moretta L"},{"initials":"DW","lastname":"McVicar","name":"McVicar DW"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"AG","lastname":"Brooks","name":"Brooks AG"},{"initials":"JP","lastname":"Vivian","name":"Vivian JP"}],"identifier":[{"id":"10.1084/jem.20152023","type":"doi"},{"id":"27045007","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"J. Exp. Med.","name":""},"pages":[null],"title":"Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition.","type":"article","url":"https://rupress.org/jem/article/213/5/791/42105/Killer-cell-immunoglobulinlike-receptor-3DL1","volume":[null],"year":[2016]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.50","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/5b39"},"rcsb":{"url":"https://www.rcsb.org/structure/5b39"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*57:01 binding \"LSSPVTKSF\" with KIR-3 NK receptor at 2.50&#8491; resolution","unique_chain_count":4}}
