{"display":true,"structure":{"allele":{"alpha":{"identifier":"uniprot:P01897","locus":"h2-l","match_type":"histo:override","mutations":[],"name":"H2-Ld","note":"Check for reason this structure doesn't match to H2-Ld","score":null,"slug":"h2_ld","species_stem":"h2"},"beta":{}},"assemblies":{"1":{"assembly_name":"6l9l_1","chains":["A","C","D","B"],"downloaded_at":"2022-11-09T14:40:34.152372"}},"assembly_count":null,"assigned_chains":{"class_i_alpha":{"chains":["A","E"],"match_type":"histo:assign_chains","score":0.74,"sequence":"GPHSMRYYETATSRRGLGEPRYTSVGYVDDKEFVRFDSDAENPRYEPQVPWMEQEGPEYWERITQIAKGQEQWFRVNLRTLLGYYNQSAGGTHTLQRMYGCDVGSDGRLLRGYEQFAYDGCDYIALNEDLRTWTAADMAAQITRRKWEQAGAAEYYRAYLEGECVEWLHRYLKNG"},"peptide":{"chains":["B","F"],"match_type":"histo:classify_peptide","sequence":"SPSYAYHQF"},"tcr_alpha":{"chains":["C"],"match_type":"stcrdab","sequence":"AKTTQPDSMESTEGETVHLPCSHATISGNEYIYWYRQVPLQGPEYVTHGLQQNTTNSMAFLAIASDRKSSTLILTHVSLRDAAVYHCILQGTGSKLSFGKGAKLTVSPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPS","subgroup":"TRAV21"},"tcr_beta":{"chains":["D"],"match_type":"stcrdab","sequence":"AVTQSPRNKVTVTGGNVTLSCRQTNSHNYMYWYRQDTGHGLRLIHYSYGAGNLQIGDVPDGYKATRTTQEDFFLLLELASPSQTSLYFCASSDGDYEQYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD","subgroup":"TRBV13"}},"chronology":{"deposition_date":"2019-11-10","deposition_year":2019,"release_date":"2020-11-18","release_year":2020,"revision_date":"2021-06-16","revision_year":2021},"class":"class_i","classical":true,"complex_type":"truncated_class_i_with_peptide_and_alpha_beta_tcr","components":["class_i_alpha","peptide","tcr_alpha","tcr_beta"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"h2-l","manually_edited":{},"missing_residues":[],"page_title":"6L9L | Truncated H2-Ld presenting \"SPSYAYHQF\" to Alpha/Beta T cell receptor","pdb_code":"6l9l","pdb_title":"1d4 TCR recognition of H2-Ld a1a2 a5 peptide complexes","peptide":{"B":{"actual_length":9,"actual_sequence":"SPSYAYHQF","chain_id":"B","features":["correct_sequence_and_length"],"full_length":9,"full_sequence":"SPSYAYHQF"},"F":{"actual_length":9,"actual_sequence":"SPSYAYHQF","chain_id":"F","features":["correct_sequence_and_length"],"full_length":9,"full_sequence":"SPSYAYHQF"}},"peptide_length":9,"peptide_length_name":"nonamer","peptide_neighbours":{"1":{"neighbours":[{"position":167,"residue":"TRP"},{"position":171,"residue":"TYR"},{"position":159,"residue":"TYR"},{"position":59,"residue":"TYR"},{"position":7,"residue":"TYR"},{"position":66,"residue":"ILE"},{"position":62,"residue":"ARG"},{"position":63,"residue":"ILE"},{"position":5,"residue":"MET"},{"position":99,"residue":"TYR"}],"position":1,"residue":"SER"},"2":{"neighbours":[{"position":99,"residue":"TYR"},{"position":159,"residue":"TYR"},{"position":7,"residue":"TYR"},{"position":66,"residue":"ILE"},{"position":63,"residue":"ILE"},{"position":45,"residue":"TYR"}],"position":2,"residue":"PRO"},"3":{"neighbours":[{"position":70,"residue":"GLN"},{"position":159,"residue":"TYR"},{"position":114,"residue":"GLU"},{"position":99,"residue":"TYR"},{"position":156,"residue":"TYR"},{"position":9,"residue":"GLU"},{"position":155,"residue":"TYR"},{"position":66,"residue":"ILE"},{"position":97,"residue":"ARG"}],"position":3,"residue":"SER"},"4":{"neighbours":[{"position":156,"residue":"TYR"},{"position":97,"residue":"ARG"},{"position":66,"residue":"ILE"},{"position":69,"residue":"GLY"},{"position":73,"residue":"TRP"},{"position":70,"residue":"GLN"},{"position":155,"residue":"TYR"}],"position":4,"residue":"TYR"},"5":{"neighbours":[{"position":73,"residue":"TRP"},{"position":116,"residue":"PHE"},{"position":155,"residue":"TYR"},{"position":156,"residue":"TYR"},{"position":97,"residue":"ARG"},{"position":70,"residue":"GLN"}],"position":5,"residue":"ALA"},"6":{"neighbours":[{"position":70,"residue":"GLN"},{"position":73,"residue":"TRP"},{"position":155,"residue":"TYR"},{"position":156,"residue":"TYR"}],"position":6,"residue":"TYR"},"7":{"neighbours":[{"position":150,"residue":"ALA"},{"position":151,"residue":"GLY"},{"position":73,"residue":"TRP"},{"position":77,"residue":"ASN"},{"position":152,"residue":"ALA"},{"position":155,"residue":"TYR"},{"position":156,"residue":"TYR"},{"position":147,"residue":"TRP"}],"position":7,"residue":"HIS"},"8":{"neighbours":[{"position":147,"residue":"TRP"},{"position":146,"residue":"LYS"},{"position":143,"residue":"THR"},{"position":76,"residue":"VAL"},{"position":73,"residue":"TRP"},{"position":77,"residue":"ASN"}],"position":8,"residue":"GLN"},"9":{"neighbours":[{"position":142,"residue":"ILE"},{"position":123,"residue":"TYR"},{"position":80,"residue":"THR"},{"position":73,"residue":"TRP"},{"position":146,"residue":"LYS"},{"position":77,"residue":"ASN"},{"position":124,"residue":"ILE"},{"position":116,"residue":"PHE"},{"position":147,"residue":"TRP"},{"position":81,"residue":"LEU"},{"position":143,"residue":"THR"},{"position":84,"residue":"TYR"},{"position":95,"residue":"LEU"}],"position":9,"residue":"PHE"}},"peptide_sequence":"SPSYAYHQF","pockets":{"a":{"a159":{"number":159,"one_letter":"Y","three_letter":"TYR"},"a163":{"number":163,"one_letter":"E","three_letter":"GLU"},"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":"I","three_letter":"ILE"},"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":"Y","three_letter":"TYR"},"a63":{"number":63,"one_letter":"I","three_letter":"ILE"},"a66":{"number":66,"one_letter":"I","three_letter":"ILE"},"a67":{"number":67,"one_letter":"A","three_letter":"ALA"},"a7":{"number":7,"one_letter":"Y","three_letter":"TYR"},"a70":{"number":70,"one_letter":"Q","three_letter":"GLN"},"a9":{"number":9,"one_letter":"E","three_letter":"GLU"},"a99":{"number":99,"one_letter":"Y","three_letter":"TYR"}},"c":{"a70":{"number":70,"one_letter":"Q","three_letter":"GLN"},"a73":{"number":73,"one_letter":"W","three_letter":"TRP"},"a74":{"number":74,"one_letter":"F","three_letter":"PHE"},"a9":{"number":9,"one_letter":"E","three_letter":"GLU"},"a97":{"number":97,"one_letter":"R","three_letter":"ARG"}},"d":{"a114":{"number":114,"one_letter":"E","three_letter":"GLU"},"a155":{"number":155,"one_letter":"Y","three_letter":"TYR"},"a156":{"number":156,"one_letter":"Y","three_letter":"TYR"},"a159":{"number":159,"one_letter":"Y","three_letter":"TYR"},"a160":{"number":160,"one_letter":"L","three_letter":"LEU"},"a99":{"number":99,"one_letter":"Y","three_letter":"TYR"}},"e":{"a114":{"number":114,"one_letter":"E","three_letter":"GLU"},"a147":{"number":147,"one_letter":"W","three_letter":"TRP"},"a152":{"number":152,"one_letter":"A","three_letter":"ALA"},"a156":{"number":156,"one_letter":"Y","three_letter":"TYR"},"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":"N","three_letter":"ASN"},"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":"L","three_letter":"LEU"}}},"publication":{"abstract":"Tumors frequently express unmutated self-tumor-associated antigens (self-TAAs). However, trial results using self-TAAs as vaccine targets against cancer are mixed, often attributed to deletion of T cells with high-affinity receptors (TCRs) for self-TAAs during T cell development. Mutating these weak self-TAAs to produce higher affinity, effective vaccines is challenging, since the mutations may not benefit all members of the broad self-TAA-specific T cell repertoire. We previously identified a common weak murine self-TAA that we converted to a highly effective antitumor vaccine by a single amino acid substitution. In this case the modified and natural self-TAAs still raised very similar sets of CD8 T cells. Our structural studies herein show that the modification of the self-TAA resulted in a subtle change in the major histocompatibility complex I-TAA structure. This amino acid substitution allowed a dramatic conformational change in the peptide during subsequent TCR engagement, creating a large increase in TCR affinity and accounting for the efficacy of the modified self-TAA as a vaccine. These results show that carefully selected, well-characterized modifications to a poorly immunogenic self-TAA can rescue the immune response of the large repertoire of weakly responding natural self-TAA-specific CD8 T cells, driving them to proliferate and differentiate into functional effectors. Subsequently, the unmodified self-TAA on the tumor cells, while unable to drive this response, is nevertheless a sufficient target for the CD8 cytotoxic effectors. Our results suggest a pathway for more efficiently identifying variants of common self-TAAs, which could be useful in vaccine development, complementing other current nonantigen-specific immunotherapies.","bibjson":{"author":[{"initials":"P","lastname":"Wei","name":"Wei P"},{"initials":"KR","lastname":"Jordan","name":"Jordan KR"},{"initials":"JD","lastname":"Buhrman","name":"Buhrman JD"},{"initials":"J","lastname":"Lei","name":"Lei J"},{"initials":"H","lastname":"Deng","name":"Deng H"},{"initials":"P","lastname":"Marrack","name":"Marrack P"},{"initials":"S","lastname":"Dai","name":"Dai S"},{"initials":"JW","lastname":"Kappler","name":"Kappler JW"},{"initials":"JE","lastname":"Slansky","name":"Slansky JE"},{"initials":"L","lastname":"Yin","name":"Yin L"}],"identifier":[{"id":"10.1073/pnas.2100588118","type":"doi"},{"id":"34074778","type":"pubmed"}],"issue":["23"],"journal":{"iso_abbreviation":"Proc Natl Acad Sci U S A","name":""},"pages":[null],"title":"Structures suggest an approach for converting weak self-peptide tumor antigens into superagonists for CD8 T cells in cancer.","type":"article","url":"https://pnas.org/doi/full/10.1073/pnas.2100588118","volume":["118"],"year":[2021]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.40","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6l9l"},"rcsb":{"url":"https://www.rcsb.org/structure/6l9l"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=6l9l"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["C"],"subgroup":"TRAV21"},"beta":{"chains":["D"],"subgroup":"TRBV13"},"mhc_type":"class_i","pdb_code":"6l9l"},"title":"Truncated H2-Ld presenting \"SPSYAYHQF\" to Alpha/Beta T cell receptor at 2.40Å resolution","unique_chain_count":4}}