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basis for strong immunogenetic associations between particular human leukocyte antigen (HLA) class I allotypes and inflammatory conditions like Beh\u00e7et's disease (HLA-B51) and ankylosing spondylitis (HLA-B27) remain mysterious. Recently, however, even stronger HLA associations are reported in drug hypersensitivities to the reverse-transcriptase inhibitor abacavir (HLA-B57), the gout prophylactic allopurinol (HLA-B58), and the antiepileptic carbamazepine (HLA-B*1502), providing a defined disease trigger and suggesting a general mechanism for these associations. We show that systemic reactions to abacavir were driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells. Recognition of abacavir required the transporter associated with antigen presentation and tapasin, was fixation sensitive, and was uniquely restricted by HLA-B*5701 and not closely related HLA allotypes with polymorphisms in the antigen-binding cleft. Hence, the strong association of HLA-B*5701 with abacavir hypersensitivity reflects specificity through creation of a unique ligand as well as HLA-restricted antigen presentation, suggesting a basis for the strong HLA class I-association with certain inflammatory disorders.","bibjson":{"author":[{"initials":"D","lastname":"Chessman","name":"Chessman D"},{"initials":"L","lastname":"Kostenko","name":"Kostenko L"},{"initials":"T","lastname":"Lethborg","name":"Lethborg T"},{"initials":"AW","lastname":"Purcell","name":"Purcell AW"},{"initials":"NA","lastname":"Williamson","name":"Williamson NA"},{"initials":"Z","lastname":"Chen","name":"Chen Z"},{"initials":"L","lastname":"Kjer-Nielsen","name":"Kjer-Nielsen L"},{"initials":"NA","lastname":"Mifsud","name":"Mifsud NA"},{"initials":"BD","lastname":"Tait","name":"Tait BD"},{"initials":"R","lastname":"Holdsworth","name":"Holdsworth R"},{"initials":"CA","lastname":"Almeida","name":"Almeida CA"},{"initials":"D","lastname":"Nolan","name":"Nolan D"},{"initials":"WA","lastname":"Macdonald","name":"Macdonald WA"},{"initials":"JK","lastname":"Archbold","name":"Archbold JK"},{"initials":"AD","lastname":"Kellerher","name":"Kellerher AD"},{"initials":"D","lastname":"Marriott","name":"Marriott D"},{"initials":"S","lastname":"Mallal","name":"Mallal S"},{"initials":"M","lastname":"Bharadwaj","name":"Bharadwaj M"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"}],"identifier":[{"id":"10.1016/j.immuni.2008.04.020","type":"doi"},{"id":"18549801","type":"pubmed"}],"issue":["6"],"journal":{"iso_abbreviation":"Immunity","name":""},"pages":["822-32"],"title":"Human leukocyte antigen class I-restricted activation of CD8+ T cells provides the immunogenetic basis of a systemic drug hypersensitivity.","type":"article","url":"https://www.sciencedirect.com/science/article/abs/pii/S1074761308002422","volume":["28"],"year":[2008]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"2.50","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/2rfx"},"rcsb":{"url":"https://www.rcsb.org/structure/2rfx"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-B*57:01 binding \"LSSPVTKSF\" at 2.50Å resolution","unique_chain_count":3}}