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leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+TRAJ21+-TRBV28+TRBJ2-3+ and TRAV4 + TRAJ8+-TRBV9+TRBJ2-1+), originating from a polyclonal T-cell repertoire, bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72. Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-160-72-HLA-B*07:02 complex, and induces differing extent of conformational change of the NY-ESO-160-72 epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition.","bibjson":{"author":[{"initials":"KF","lastname":"Chan","name":"Chan KF"},{"initials":"BS","lastname":"Gully","name":"Gully BS"},{"initials":"S","lastname":"Gras","name":"Gras S"},{"initials":"DX","lastname":"Beringer","name":"Beringer DX"},{"initials":"L","lastname":"Kjer-Nielsen","name":"Kjer-Nielsen L"},{"initials":"J","lastname":"Cebon","name":"Cebon J"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"W","lastname":"Chen","name":"Chen W"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"}],"identifier":[{"id":"10.1038/s41467-018-03321-w","type":"doi"},{"id":"29531227","type":"pubmed"}],"issue":["1"],"journal":{"iso_abbreviation":"Nat Commun","name":""},"pages":["1026"],"title":"Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.","type":"article","url":"http://www.nature.com/articles/s41467-018-03321-w","volume":["9"],"year":[2018]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.03","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6avf"},"rcsb":{"url":"https://www.rcsb.org/structure/6avf"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=6avf"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["A"],"subgroup":"TRAV4"},"beta":{"chains":["B"],"subgroup":"TRBV28"},"mhc_type":"class_i","pdb_code":"6avf"},"title":"HLA-B*07:02 presenting \"APRGPHGGAASGL\" to Alpha/Beta T cell receptor at 2.03Å resolution","unique_chain_count":5}}