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selection of the T cell repertoire, the immune system navigates the subtle distinction between self-restriction and self-tolerance, yet how this is achieved is unclear. Here we describe how self-tolerance toward a trans-HLA (human leukocyte antigen) allotype shapes T cell receptor (TCR) recognition of an Epstein-Barr virus (EBV) determinant (FLRGRAYGL). The recognition of HLA-B8-FLRGRAYGL by two archetypal TCRs was compared. One was a publicly selected TCR, LC13, that is alloreactive with HLA-B44; the other, CF34, lacks HLA-B44 reactivity because it arises when HLA-B44 is coinherited in trans with HLA-B8. Whereas the alloreactive LC13 TCR docked at the C terminus of HLA-B8-FLRGRAYGL, the CF34 TCR docked at the N terminus of HLA-B8-FLRGRAYGL, which coincided with a polymorphic region between HLA-B8 and HLA-B44. The markedly contrasting footprints of the LC13 and CF34 TCRs provided a portrait of how self-tolerance shapes the specificity of TCRs selected into the immune repertoire.","bibjson":{"author":[{"initials":"S","lastname":"Gras","name":"Gras S"},{"initials":"SR","lastname":"Burrows","name":"Burrows SR"},{"initials":"L","lastname":"Kjer-Nielsen","name":"Kjer-Nielsen L"},{"initials":"CS","lastname":"Clements","name":"Clements CS"},{"initials":"YC","lastname":"Liu","name":"Liu YC"},{"initials":"LC","lastname":"Sullivan","name":"Sullivan LC"},{"initials":"MJ","lastname":"Bell","name":"Bell MJ"},{"initials":"AG","lastname":"Brooks","name":"Brooks AG"},{"initials":"AW","lastname":"Purcell","name":"Purcell AW"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"}],"identifier":[{"id":"10.1016/j.immuni.2008.11.011","type":"doi"},{"id":"19167249","type":"pubmed"}],"issue":["2"],"journal":{"iso_abbreviation":"Immunity","name":""},"pages":["193-203"],"title":"The shaping of T cell receptor recognition by self-tolerance.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S1074761309000612","volume":["30"],"year":[2009]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"2.80","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/3ffc"},"rcsb":{"url":"https://www.rcsb.org/structure/3ffc"},"stcrdab":{"url":"http://opig.stats.ox.ac.uk/webapps/stcrdab/StrViewer?pdb=3ffc"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":{"alpha":{"chains":["D"],"subgroup":"TRAV14"},"beta":{"chains":["E"],"subgroup":"TRBV11"},"mhc_type":"class_i","pdb_code":"3ffc"},"title":"HLA-B*08:01 presenting \"FLRGRAYGL\" to Alpha/Beta T cell receptor at 2.80&#8491; resolution","unique_chain_count":5}}
