{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:26:13Z","timestamp":1792027573717,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T00:00:00Z","timestamp":1689292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Allopurinol (ALP) is a successful drug used in the treatment of gout. However, this drug has been implicated in hypersensitivity reactions that can cause severe to life\u2010threatening reactions such as Stevens\u2013Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Individuals who carry the human leukocyte antigen (HLA)\u2010B*58:01 allotype are at higher risk of experiencing a hypersensitivity reaction (odds ratios ranging from 5.62 to 580.3 for mild to severe reactions, respectively). In addition to the parent drug, the metabolite oxypurinol (OXP) is implicated in triggering T cell\u2010mediated immunopathology via a labile interaction with HLA\u2010B*58:01. To date, there has been limited information regarding the T\u2010cell receptor (TCR) repertoire usage of reactive T cells in patients with ALP\u2010induced SJS or TEN and, in particular, there are no reports examining paired \u03b1\u03b2TCRs. Here, using in vitro drug\u2010treated PBMCs isolated from both resolved ALP\u2010induced SJS\/TEN cases and drug\u2010na\u00efve healthy donors, we show that OXP is the driver of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010mediated responses and that drug\u2010exposed memory T cells can exhibit a proinflammatory immunophenotype similar to T cells described during active disease. Furthermore, this response supported the pharmacological interaction with immune receptors (p\u2010i) concept by showcasing (i) the labile metabolite interaction with peptide\/HLA complexes, (ii) immunogenic complex formation at the cell surface, and (iii) lack of requirement for antigen processing to elicit drug\u2010induced T cell responsiveness. Examination of paired OXP\u2010induced \u03b1\u03b2TCR repertoires highlighted an oligoclonal and private clonotypic profile in both resolved ALP\u2010induced SJS\/TEN cases and drug\u2010na\u00efve healthy donors.\n                  <\/jats:p>","DOI":"10.1111\/all.15814","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T01:49:18Z","timestamp":1689385758000},"page":"2980-2993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The allopurinol metabolite, oxypurinol, drives oligoclonal expansions of drug\u2010reactive T cells in resolved hypersensitivity cases and drug\u2010na\u00efve healthy donors"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8647-2102","authenticated-orcid":false,"given":"Nicole A.","family":"Mifsud","sequence":"first","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3870-0796","authenticated-orcid":false,"given":"Patricia T.","family":"Illing","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Ho","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9286-8186","authenticated-orcid":false,"given":"Johanna E.","family":"Tuomisto","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5784-3338","authenticated-orcid":false,"given":"Heidi","family":"Fettke","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-1198","authenticated-orcid":false,"given":"Kerry A.","family":"Mullan","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8597-815X","authenticated-orcid":false,"given":"James","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-7522","authenticated-orcid":false,"given":"Jamie","family":"Rossjohn","sequence":"additional","affiliation":[{"name":"Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University  Clayton Victoria Australia"},{"name":"Institute of Infection and Immunity Cardiff University School of Medicine  Cardiff 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