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nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.","bibjson":{"author":[{"initials":"C","lastname":"Barber","name":"Barber C"},{"initials":"VA","lastname":"De Souza","name":"De Souza VA"},{"initials":"RL","lastname":"Paterson","name":"Paterson RL"},{"initials":"M","lastname":"Martin-Urdiroz","name":"Martin-Urdiroz M"},{"initials":"NC","lastname":"Mulakkal","name":"Mulakkal NC"},{"initials":"V","lastname":"Srikannathasan","name":"Srikannathasan V"},{"initials":"M","lastname":"Connolly","name":"Connolly M"},{"initials":"G","lastname":"Phillips","name":"Phillips G"},{"initials":"T","lastname":"Foong-Leong","name":"Foong-Leong T"},{"initials":"R","lastname":"Pengelly","name":"Pengelly R"},{"initials":"V","lastname":"Karuppiah","name":"Karuppiah V"},{"initials":"T","lastname":"Grant","name":"Grant T"},{"initials":"M","lastname":"Dembek","name":"Dembek M"},{"initials":"A","lastname":"Verma","name":"Verma A"},{"initials":"D","lastname":"Gibbs-Howe","name":"Gibbs-Howe D"},{"initials":"TH","lastname":"Blicher","name":"Blicher TH"},{"initials":"A","lastname":"Knox","name":"Knox A"},{"initials":"RA","lastname":"Robinson","name":"Robinson RA"},{"initials":"DK","lastname":"Cole","name":"Cole DK"},{"initials":"S","lastname":"Leonard","name":"Leonard S"}],"identifier":[{"id":"10.1002/eji.202149745","type":"doi"},{"id":"35108401","type":"pubmed"}],"issue":["4"],"journal":{"iso_abbreviation":"Eur J Immunol","name":""},"pages":["618-632"],"title":"Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.","type":"article","url":"https://onlinelibrary.wiley.com/doi/10.1002/eji.202149745","volume":["52"],"year":[2022]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.65","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6zky"},"rcsb":{"url":"https://www.rcsb.org/structure/6zky"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=6zky"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["D"],"subgroup":"TRAV21"},"beta":{"chains":["E"],"subgroup":"TRBV6"},"mhc_type":"class_i","pdb_code":"6zky"},"title":"HLA-E*01:03 presenting \"RLPAKAPL\" to Alpha/Beta T cell receptor at 2.65&#8491; resolution","unique_chain_count":5}}
