{"display":true,"structure":{"allele":{"alpha":{"identifier":"uniprot:P01899","locus":"h2-d","match_type":"histo:fuzzy","name":"H2-Db","slug":"h2_db","species_stem":"H2"},"beta":{}},"assemblies":{"1":{"assembly_name":"6mp0_1","chains":["A"],"downloaded_at":"2022-11-09T14:41:29.401220"}},"assembly_count":null,"assigned_chains":{"class_i_alpha":{"chains":["A"],"match_type":"histo:assign_chains","score":0.76,"sequence":"TAPDNLGYMGGGGSGGGGSGGGGSIQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDMGGGGSGGGGSGGGGSGGGGSGPHSMRYFETAVSRPGLEEPRYISVGYVDNKEFVRFDSDAENPRYEPRAPWMEQEGPEYWERETQKAKGQEQWFRVSLRNLLGAYNQSAGGSHTLQQMSGCDLGSDWRLLRGYLQFAYEGRDYIALNEDLKTWTAADMAAQITRRKWEQSGAAEHYKAYLEGECVEWLHRYLKNGNATLLRTDSPKAHVTHHPRSKGEVTLRCWALGFYPADITLTWQLNGEELTQDMELVETRPAGDGTFQKWASVVVPLGKEQNYTCRVYHEGLPEPLTLRWEPAAAGGGLNDIFEAQKIEWHEHHHHHHHH"}},"chronology":{"deposition_date":"2018-10-05","deposition_year":2018,"release_date":"2018-11-07","release_year":2018,"revision_date":"2020-07-29","revision_year":2020},"class":"class_i","classical":true,"complex_type":"single_chain_class_i_construct","components":["class_i_alpha"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"h2-d","manually_edited":{},"missing_residues":[],"page_title":"6MP0 | Single chain construct of H2-Db binding \"None\"","pdb_code":"6mp0","pdb_title":"Crystal structures of the murine Class I major histocompatibility complex h-2db in complex with the trp1-m9 peptide","peptide":{"actual_sequence":null,"epitope_info":{},"features":[],"full_sequence":null,"gap_info":{},"gapped_sequence":null,"length":{"numeric":null,"text":null},"unnatural_amino_acids":[]},"pockets":{"a":{"a159":{"number":159,"one_letter":"G","three_letter":"GLY"},"a163":{"number":163,"one_letter":"P","three_letter":"PRO"},"a167":{"number":167,"one_letter":"S","three_letter":"SER"},"a171":{"number":171,"one_letter":"V","three_letter":"VAL"},"a5":{"number":5,"one_letter":"N","three_letter":"ASN"},"a59":{"number":59,"one_letter":"I","three_letter":"ILE"},"a63":{"number":63,"one_letter":"M","three_letter":"MET"},"a66":{"number":66,"one_letter":"N","three_letter":"ASN"},"a7":{"number":7,"one_letter":"G","three_letter":"GLY"}},"b":{"a24":{"number":24,"one_letter":"S","three_letter":"SER"},"a34":{"number":34,"one_letter":"Y","three_letter":"TYR"},"a45":{"number":45,"one_letter":"N","three_letter":"ASN"},"a63":{"number":63,"one_letter":"M","three_letter":"MET"},"a66":{"number":66,"one_letter":"N","three_letter":"ASN"},"a67":{"number":67,"one_letter":"G","three_letter":"GLY"},"a7":{"number":7,"one_letter":"G","three_letter":"GLY"},"a70":{"number":70,"one_letter":"I","three_letter":"ILE"},"a9":{"number":9,"one_letter":"M","three_letter":"MET"},"a99":{"number":99,"one_letter":"T","three_letter":"THR"}},"c":{"a70":{"number":70,"one_letter":"I","three_letter":"ILE"},"a73":{"number":73,"one_letter":"V","three_letter":"VAL"},"a74":{"number":74,"one_letter":"E","three_letter":"GLU"},"a9":{"number":9,"one_letter":"M","three_letter":"MET"},"a97":{"number":97,"one_letter":"T","three_letter":"THR"}},"d":{"a114":{"number":114,"one_letter":"P","three_letter":"PRO"},"a155":{"number":155,"one_letter":"V","three_letter":"VAL"},"a156":{"number":156,"one_letter":"S","three_letter":"SER"},"a159":{"number":159,"one_letter":"G","three_letter":"GLY"},"a160":{"number":160,"one_letter":"L","three_letter":"LEU"},"a99":{"number":99,"one_letter":"T","three_letter":"THR"}},"e":{"a114":{"number":114,"one_letter":"P","three_letter":"PRO"},"a147":{"number":147,"one_letter":"S","three_letter":"SER"},"a152":{"number":152,"one_letter":"E","three_letter":"GLU"},"a156":{"number":156,"one_letter":"S","three_letter":"SER"},"a97":{"number":97,"one_letter":"T","three_letter":"THR"}},"f":{"a116":{"number":116,"one_letter":"T","three_letter":"THR"},"a123":{"number":123,"one_letter":"M","three_letter":"MET"},"a143":{"number":143,"one_letter":"S","three_letter":"SER"},"a146":{"number":146,"one_letter":"H","three_letter":"HIS"},"a147":{"number":147,"one_letter":"S","three_letter":"SER"},"a77":{"number":77,"one_letter":"D","three_letter":"ASP"},"a80":{"number":80,"one_letter":"F","three_letter":"PHE"},"a81":{"number":81,"one_letter":"S","three_letter":"SER"},"a84":{"number":84,"one_letter":"W","three_letter":"TRP"},"a95":{"number":95,"one_letter":"T","three_letter":"THR"}}},"publication":{"abstract":"T-cell priming occurs when a na\u00efve T cell recognizes cognate peptide-MHC complexes on an activated antigen-presenting cell. The circumstances of this initial priming have ramifications on the fate of the newly primed T cell. Newly primed CD8<sup>+</sup> T cells can embark onto different trajectories, with some becoming short-lived effector cells and others adopting a tissue resident or memory cell fate. To determine whether T-cell priming influences the quality of the effector T-cell response to tumors, we used transnuclear CD8<sup>+</sup> T cells that recognize the melanoma antigen TRP1 using TRP1<sup>high</sup> or TRP1<sup>low</sup> TCRs that differ in both affinity and fine specificity. From a series of altered peptide ligands, we identified a point mutation (K8) in a nonanchor residue that, when analyzed crystallographically and biophysically, destabilized the peptide interaction with the MHC binding groove. <i>In vitro</i>, the K8 peptide induced robust proliferation of both TRP1<sup>high</sup> and TRP1<sup>low</sup> CD8<sup>+</sup> T cells but did not induce expression of PD-1. Cytokine production from K8-stimulated TRP1 cells was minimal, whereas cytotoxicity was increased. Upon transfer into B16 tumor-bearing mice, the reference peptide (TRP1-M9)- and K8-stimulated TRP1 cells were equally effective at controlling tumor growth but accomplished this through different mechanisms. TRP1-M9-stimulated cells produced more IFN\u03b3, whereas K8-stimulated cells accumulated to higher numbers and were more cytotoxic. We, therefore, conclude that TCR recognition of weakly binding peptides during priming can skew the effector function of tumor-specific CD8<sup>+</sup> T cells.","bibjson":{"author":[{"initials":"E","lastname":"Clancy-Thompson","name":"Clancy-Thompson E"},{"initials":"CA","lastname":"Devlin","name":"Devlin CA"},{"initials":"PM","lastname":"Tyler","name":"Tyler PM"},{"initials":"MM","lastname":"Servos","name":"Servos MM"},{"initials":"LR","lastname":"Ali","name":"Ali LR"},{"initials":"KS","lastname":"Ventre","name":"Ventre KS"},{"initials":"MA","lastname":"Bhuiyan","name":"Bhuiyan MA"},{"initials":"PT","lastname":"Bruck","name":"Bruck PT"},{"initials":"ME","lastname":"Birnbaum","name":"Birnbaum ME"},{"initials":"SK","lastname":"Dougan","name":"Dougan SK"}],"identifier":[{"id":"10.1158/2326-6066.CIR-18-0348","type":"doi"},{"id":"30352798","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Cancer Immunol Res","name":""},"pages":[null],"title":"Altered binding of tumor antigenic peptides to MHC class I affects CD8 T cell effector responses.","type":"article","url":"https://aacrjournals.org/cancerimmunolres/article/6/12/1524/468917/Altered-Binding-of-Tumor-Antigenic-Peptides-to-MHC","volume":[null],"year":[2018]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"2.00","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6mp0"},"rcsb":{"url":"https://www.rcsb.org/structure/6mp0"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":null,"title":"Single chain construct of H2-Db binding \"None\" at 2.00&#8491; resolution","unique_chain_count":1}}