{"display":true,"structure":{"allele":{"alpha":{"identifier":"ipd-imgt:HLA34729","locus":"hla-b","match_type":"histo:exact","name":"HLA-B*37:01","slug":"hla_b_37_01","species_stem":"hla"},"beta":{}},"assemblies":{"1":{"assembly_name":"6mt4_1","chains":["A","B","C"],"downloaded_at":"2022-11-09T14:26:43.006474"}},"assembly_count":null,"assigned_chains":{"beta2m":{"chains":["B"],"match_type":"histo:assign_chains","score":0.99,"sequence":"MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM"},"class_i_alpha":{"chains":["A"],"match_type":"histo:assign_chains","score":0.94,"sequence":"GSHSMRYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYWDRETQISKTNTQTYREDLRTLLRYYNQSEAGSHTIQRMSGCDVGPDGRLLRGYNQFAYDGKDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQDRAYLEGTCVEWLRRYLENGKETLQRADPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEP"},"peptide":{"chains":["C"],"match_type":"histo:classify_peptide","sequence":"FEDLRVSSF"}},"chronology":{"deposition_date":"2018-10-19","deposition_year":2018,"release_date":"2019-02-13","release_year":2019,"revision_date":"2019-02-13","revision_year":2019},"class":"class_i","classical":true,"complex_type":"class_i_with_peptide","components":["class_i_alpha","beta2m","peptide"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"hla-b","manually_edited":{},"missing_residues":[],"page_title":"6MT4 | HLA-B*37:01 binding \"FEDLRVSSF\"","pdb_code":"6mt4","pdb_title":"Crystal structure of hla-b*37:01 in complex with np338-l7s influenza peptide","peptide":{"C":{"actual_length":9,"actual_sequence":"FEDLRVSSF","chain_id":"C","features":["correct_sequence_and_length"],"full_length":9,"full_sequence":"FEDLRVSSF"}},"peptide_length":9,"peptide_length_name":"nonamer","peptide_neighbours":{"1":{"neighbours":[{"position":62,"residue":"ARG"},{"position":159,"residue":"TYR"},{"position":167,"residue":"TRP"},{"position":171,"residue":"TYR"},{"position":7,"residue":"TYR"},{"position":163,"residue":"THR"},{"position":63,"residue":"GLU"},{"position":5,"residue":"MET"},{"position":33,"residue":"PHE"},{"position":59,"residue":"TYR"},{"position":66,"residue":"ILE"}],"position":1,"residue":"PHE"},"2":{"neighbours":[{"position":63,"residue":"GLU"},{"position":70,"residue":"ASN"},{"position":9,"residue":"HIS"},{"position":66,"residue":"ILE"},{"position":24,"residue":"SER"},{"position":159,"residue":"TYR"},{"position":67,"residue":"SER"},{"position":7,"residue":"TYR"}],"position":2,"residue":"GLU"},"3":{"neighbours":[{"position":66,"residue":"ILE"},{"position":163,"residue":"THR"},{"position":63,"residue":"GLU"},{"position":70,"residue":"ASN"},{"position":159,"residue":"TYR"},{"position":97,"residue":"ARG"}],"position":3,"residue":"ASP"},"4":{"neighbours":[{"position":66,"residue":"ILE"},{"position":69,"residue":"THR"},{"position":65,"residue":"GLN"},{"position":70,"residue":"ASN"}],"position":4,"residue":"LEU"},"5":{"neighbours":[{"position":70,"residue":"ASN"},{"position":77,"residue":"ASP"},{"position":116,"residue":"PHE"},{"position":97,"residue":"ARG"},{"position":73,"residue":"THR"},{"position":74,"residue":"TYR"},{"position":147,"residue":"TRP"}],"position":5,"residue":"ARG"},"6":{"neighbours":[{"position":155,"residue":"GLN"},{"position":156,"residue":"ASP"},{"position":152,"residue":"VAL"}],"position":6,"residue":"VAL"},"7":{"neighbours":[{"position":146,"residue":"LYS"},{"position":73,"residue":"THR"},{"position":147,"residue":"TRP"},{"position":152,"residue":"VAL"}],"position":7,"residue":"SER"},"8":{"neighbours":[{"position":73,"residue":"THR"},{"position":76,"residue":"GLU"},{"position":143,"residue":"THR"},{"position":77,"residue":"ASP"},{"position":147,"residue":"TRP"},{"position":146,"residue":"LYS"}],"position":8,"residue":"SER"},"9":{"neighbours":[{"position":84,"residue":"TYR"},{"position":147,"residue":"TRP"},{"position":81,"residue":"LEU"},{"position":146,"residue":"LYS"},{"position":116,"residue":"PHE"},{"position":95,"residue":"ILE"},{"position":143,"residue":"THR"},{"position":80,"residue":"THR"},{"position":142,"residue":"ILE"},{"position":77,"residue":"ASP"},{"position":123,"residue":"TYR"},{"position":124,"residue":"ILE"}],"position":9,"residue":"PHE"}},"peptide_sequence":"FEDLRVSSF","pockets":{"a":{"a159":{"number":159,"one_letter":"Y","three_letter":"TYR"},"a163":{"number":163,"one_letter":"T","three_letter":"THR"},"a167":{"number":167,"one_letter":"W","three_letter":"TRP"},"a171":{"number":171,"one_letter":"Y","three_letter":"TYR"},"a5":{"number":5,"one_letter":"M","three_letter":"MET"},"a59":{"number":59,"one_letter":"Y","three_letter":"TYR"},"a63":{"number":63,"one_letter":"E","three_letter":"GLU"},"a66":{"number":66,"one_letter":"I","three_letter":"ILE"},"a7":{"number":7,"one_letter":"Y","three_letter":"TYR"}},"b":{"a24":{"number":24,"one_letter":"S","three_letter":"SER"},"a34":{"number":34,"one_letter":"V","three_letter":"VAL"},"a45":{"number":45,"one_letter":"T","three_letter":"THR"},"a63":{"number":63,"one_letter":"E","three_letter":"GLU"},"a66":{"number":66,"one_letter":"I","three_letter":"ILE"},"a67":{"number":67,"one_letter":"S","three_letter":"SER"},"a7":{"number":7,"one_letter":"Y","three_letter":"TYR"},"a70":{"number":70,"one_letter":"N","three_letter":"ASN"},"a9":{"number":9,"one_letter":"H","three_letter":"HIS"},"a99":{"number":99,"one_letter":"S","three_letter":"SER"}},"c":{"a70":{"number":70,"one_letter":"N","three_letter":"ASN"},"a73":{"number":73,"one_letter":"T","three_letter":"THR"},"a74":{"number":74,"one_letter":"Y","three_letter":"TYR"},"a9":{"number":9,"one_letter":"H","three_letter":"HIS"},"a97":{"number":97,"one_letter":"R","three_letter":"ARG"}},"d":{"a114":{"number":114,"one_letter":"N","three_letter":"ASN"},"a155":{"number":155,"one_letter":"Q","three_letter":"GLN"},"a156":{"number":156,"one_letter":"D","three_letter":"ASP"},"a159":{"number":159,"one_letter":"Y","three_letter":"TYR"},"a160":{"number":160,"one_letter":"L","three_letter":"LEU"},"a99":{"number":99,"one_letter":"S","three_letter":"SER"}},"e":{"a114":{"number":114,"one_letter":"N","three_letter":"ASN"},"a147":{"number":147,"one_letter":"W","three_letter":"TRP"},"a152":{"number":152,"one_letter":"V","three_letter":"VAL"},"a156":{"number":156,"one_letter":"D","three_letter":"ASP"},"a97":{"number":97,"one_letter":"R","three_letter":"ARG"}},"f":{"a116":{"number":116,"one_letter":"F","three_letter":"PHE"},"a123":{"number":123,"one_letter":"Y","three_letter":"TYR"},"a143":{"number":143,"one_letter":"T","three_letter":"THR"},"a146":{"number":146,"one_letter":"K","three_letter":"LYS"},"a147":{"number":147,"one_letter":"W","three_letter":"TRP"},"a77":{"number":77,"one_letter":"D","three_letter":"ASP"},"a80":{"number":80,"one_letter":"T","three_letter":"THR"},"a81":{"number":81,"one_letter":"L","three_letter":"LEU"},"a84":{"number":84,"one_letter":"Y","three_letter":"TYR"},"a95":{"number":95,"one_letter":"I","three_letter":"ILE"}}},"publication":{"abstract":"Newly-emerged and vaccine-mismatched influenza A viruses (IAVs) result in a rapid global spread of the virus due to minimal antibody-mediated immunity. In that case, established CD8+ T-cells can reduce disease severity. However, as mutations occur sporadically within immunogenic IAV-derived T-cell peptides, understanding of T-cell receptor (TCR\u03b1\u03b2) cross-reactivity towards IAV variants is needed for a vaccine design. Here, we investigate TCR\u03b1\u03b2 cross-strain recognition across IAV variants within two immunodominant human IAV-specific CD8+ T-cell epitopes, HLA-B*37:01-restricted NP338-346 (B37-NP338) and HLA-A*01:01-restricted NP44-52 (A1-NP44). We find high abundance of cross-reactive TCR\u03b1\u03b2 clonotypes recognizing distinct IAV variants. Structures of the wild-type and variant peptides revealed preserved conformation of the bound peptides. Structures of a cross-reactive TCR-HLA-B37-NP338 complex suggest that the conserved conformation of the variants underpins TCR cross-reactivity. Overall, cross-reactive CD8+ T-cell responses, underpinned by conserved epitope structure, facilitates recognition of distinct IAV variants, thus CD8+ T-cell-targeted vaccines could provide protection across different IAV strains.","bibjson":{"author":[{"initials":"EJ","lastname":"Grant","name":"Grant EJ"},{"initials":"TM","lastname":"Josephs","name":"Josephs TM"},{"initials":"L","lastname":"Loh","name":"Loh L"},{"initials":"EB","lastname":"Clemens","name":"Clemens EB"},{"initials":"S","lastname":"Sant","name":"Sant S"},{"initials":"M","lastname":"Bharadwaj","name":"Bharadwaj M"},{"initials":"W","lastname":"Chen","name":"Chen W"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"S","lastname":"Gras","name":"Gras S"},{"initials":"K","lastname":"Kedzierska","name":"Kedzierska K"}],"identifier":[{"id":"10.1038/s41467-018-07815-5","type":"doi"},{"id":"30575715","type":"pubmed"}],"issue":["1"],"journal":{"iso_abbreviation":"Nat Commun","name":""},"pages":["5427"],"title":"Broad CD8<sub>+</sub> T cell cross-recognition of distinct influenza A strains in humans.","type":"article","url":"http://www.nature.com/articles/s41467-018-07815-5","volume":["9"],"year":[2018]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"1.55","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6mt4"},"rcsb":{"url":"https://www.rcsb.org/structure/6mt4"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*37:01 binding \"FEDLRVSSF\" at 1.55&#8491; resolution","unique_chain_count":3}}