{"display":true,"structure":{"allele":{"alpha":{"identifier":"ipd-imgt:HLA35266","locus":"hla-a","match_type":"histo:exact","name":"HLA-A*02:01","slug":"hla_a_02_01","species_stem":"hla"},"beta":{}},"assemblies":{"1":{"assembly_name":"6bnl_1","chains":["A","B","C","D","I"],"downloaded_at":"2022-11-09T14:39:08.466200"}},"assembly_count":null,"assigned_chains":{"beta2m":{"chains":["B","F"],"match_type":"histo:assign_chains","score":1.0,"sequence":"IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM"},"cd1d":{"chains":["A","E"],"match_type":"histo:assign_chains","score":1.0,"sequence":"SEAQQKNYTFRCLQMSSFANRSWSRTDSVVWLGDLQTHRWSNDSATISFTKPWSQGKLSNQQWEKLQHMFQVYRVSFTRDIQELVKMMSPKEDYPIEIQLSAGCEMYPGNASESFLHVAFQGKYVVRFWGTSWQTVPGAPSWLDLPIKVLNADQGTSATVQMLLNDTCPLFVRGLLEAGKSDLEKQEKPVAWLSSVPSSAHGHRQLVCHVSGFYPKPVWVMWMRGDQEQQGTHRGDFLPNADETWYLQATLDVEAGEEAGLACRVKHSSLGGQDIILYWGSLHHILDAQKMVWNHRHHHHHH"},"tcr_alpha":{"chains":["C"],"match_type":"stcrdab","sequence":"TQVEQSPQSLVVRQGENSVLQCNYSVTPDNHLRWFKQDTGKGLVSLTVLVDQKDKTSNGRYSATLDKDAKHSTLHITATLLDDTATYICVVGDRGSALGRLHFGAGTQLIVIPDIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKCVLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESS","subgroup":"TRAV11"},"tcr_beta":{"chains":["D"],"match_type":"stcrdab","sequence":"MEAAVTQSPRNKVAVTGGKVTLSCNQTNNHNNMYWYRQDTGHGLRLIHYSYGAGSTEKGDIPDGYKASRPSQENFSLILELATPSQTSVYFCASGDEGYTQYFGPGTRLLVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVCTDPQPLKEQPALNDSRYALSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRAD","subgroup":"TRBV13"}},"chronology":{"deposition_date":"2017-11-16","deposition_year":2017,"release_date":"2018-04-04","release_year":2018,"revision_date":"2020-07-29","revision_year":2020},"class":"class_i","classical":false,"complex_type":"cd1d_with_nkt_alpha_beta_tcr","components":["cd1d","beta2m","tcr_alpha","tcr_beta"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"hla-a","manually_edited":{},"missing_residues":[],"page_title":"6BNL | Non-classical MHC Class I molecule CD1d with Natural Killer Alpha/Beta T cell receptor","pdb_code":"6bnl","pdb_title":"Crystal structure of TCR-MHC-like molecule","peptide":{"actual_sequence":null,"epitope_info":{},"features":[],"full_sequence":null,"gap_info":{},"gapped_sequence":null,"length":{"numeric":null,"text":null},"unnatural_amino_acids":[]},"publication":{"abstract":"Glycosylceramides that activate CD1d-restricted invariant natural killer T (iNKT) cells have potential therapeutic applications for augmenting immune responses against cancer and infections. Previous studies using mouse models identified sphinganine variants of \u03b1-galactosylceramide as promising iNKT cell activators that stimulate cytokine responses with a strongly proinflammatory bias. However, the activities of sphinganine variants in mice have generally not translated well to studies of human iNKT cell responses. Here, we show that strongly proinflammatory and anti-tumor iNKT cell responses were achieved in mice by a variant of \u03b1-galactosylceramide that combines a sphinganine base with a hydrocinnamoyl ester on C6\u2033 of the sugar. Importantly, the activities observed with this variant were largely preserved for human iNKT cell responses. Structural and in silico modeling studies provided a mechanistic basis for these findings and suggested basic principles for capturing useful properties of sphinganine analogs of synthetic iNKT cell activators in the design of immunotherapeutic agents.","bibjson":{"author":[{"initials":"D","lastname":"Chennamadhavuni","name":"Chennamadhavuni D"},{"initials":"NA","lastname":"Saavedra-Avila","name":"Saavedra-Avila NA"},{"initials":"LJ","lastname":"Carre\u00f1o","name":"Carre\u00f1o LJ"},{"initials":"MJ","lastname":"Guberman-Pfeffer","name":"Guberman-Pfeffer MJ"},{"initials":"P","lastname":"Arora","name":"Arora P"},{"initials":"T","lastname":"Yongqing","name":"Yongqing T"},{"initials":"R","lastname":"Pryce","name":"Pryce R"},{"initials":"HF","lastname":"Koay","name":"Koay HF"},{"initials":"DI","lastname":"Godfrey","name":"Godfrey DI"},{"initials":"S","lastname":"Keshipeddy","name":"Keshipeddy S"},{"initials":"SK","lastname":"Richardson","name":"Richardson SK"},{"initials":"S","lastname":"Sundararaj","name":"Sundararaj S"},{"initials":"JH","lastname":"Lo","name":"Lo JH"},{"initials":"X","lastname":"Wen","name":"Wen X"},{"initials":"JA","lastname":"Gasc\u00f3n","name":"Gasc\u00f3n JA"},{"initials":"W","lastname":"Yuan","name":"Yuan W"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"J","lastname":"Le Nours","name":"Le Nours J"},{"initials":"SA","lastname":"Porcelli","name":"Porcelli SA"},{"initials":"AR","lastname":"Howell","name":"Howell AR"}],"identifier":[{"id":"10.1016/j.chembiol.2018.02.009","type":"doi"},{"id":"29576533","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Cell Chem Biol","name":""},"pages":[null],"title":"Dual Modifications of \ufffd\ufffd-Galactosylceramide Synergize to Promote Activation of Human Invariant Natural Killer T Cells and Stimulate Anti-tumor Immunity.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S2451945618300734","volume":[null],"year":[2018]},"in_pmc":"N","in_pmce":"Y","open_access":"N"},"resolution":"2.60","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6bnl"},"rcsb":{"url":"https://www.rcsb.org/structure/6bnl"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=6bnl"}},"species":{"common_name":"Mouse","match_type":"histo:assign_species","scientific_name":"Mus musculus","slug":"mus_musculus"},"tcr":{"alpha":{"chains":["C"],"subgroup":"TRAV11"},"beta":{"chains":["D"],"subgroup":"TRBV13"},"pdb_code":"6bnl"},"title":"Non-classical MHC Class I molecule CD1d with Natural Killer Alpha/Beta T cell receptor at 2.60Å resolution","unique_chain_count":4}}