{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:32:43Z","timestamp":1790652763815,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,6,27]],"date-time":"2021-06-27T00:00:00Z","timestamp":1624752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BBSRC\/GSK Industrial Partnership","award":["BB\/R008108\/1"],"award-info":[{"award-number":["BB\/R008108\/1"]}]},{"name":"MRC Centre for Drug Safety Science","award":["G0700654"],"award-info":[{"award-number":["G0700654"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug rash with eosinophilia with systemic symptoms (DRESS) is a serious adverse event associated with use of the glycopeptide antibiotic vancomycin. Vancomycin-induced drug rash with eosinophilia with systemic symptoms is associated with the expression of human leukocyte antigen (HLA)-A*32:01, suggesting that the drug interacts with this HLA to activate CD8+ T cells. The purpose of this study was to utilize peripheral blood mononuclear cell from healthy donors to: (1) investigate whether expression of HLA-A*32:01 is critical for the priming na\u00efve of T cells with vancomycin and (2) generate T-cell clones (TCC) to determine whether vancomycin exclusively activates CD8+ T cells and to define cellular phenotype, pathways of drug presentation and cross-reactivity. Dendritic cells were cultured with na\u00efve T cells and vancomycin for 2\u2009weeks. On day 14, cells were restimulated with vancomycin and T-cell proliferation was assessed by [3H]-thymidine incorporation. Vancomycin-specific TCC were generated by serial dilution and repetitive mitogen stimulation. Na\u00efve T cells from HLA-A*02:01 positive and negative donors were activated with vancomycin; however the strength of the induced response was significantly stronger in donors expressing HLA-A*32:01. Vancomycin-responsive CD4+ and CD8+ TCC from HLA-A*32:01+ donors expressed high levels of CXCR3 and CCR4, and secreted IFN-\u03b3, IL-13, and cytolytic molecules. Activation of CD8+ TCC was HLA class I-restricted and dependent on a direct vancomycin HLA binding interaction with no requirement for processing. Several TCC displayed cross-reactivity with teicoplanin and daptomycin. To conclude, this study provides evidence that vancomycin primes na\u00efve T cells from healthy donors expressing HLA-A*32:01 through a direct pharmacological binding interaction. Cross-reactivity of CD8+ TCC with teicoplanin provides an explanation for the teicoplanin reactions observed in vancomycin hypersensitive patients.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab084","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T11:10:05Z","timestamp":1624619405000},"page":"139-153","source":"Crossref","is-referenced-by-count":19,"title":["Deciphering Adverse Drug Reactions:<i>In Vitro<\/i>Priming and Characterization of Vancomycin-Specific T Cells From Healthy Donors Expressing HLA-A*32:01"],"prefix":"10.1093","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1873-4032","authenticated-orcid":false,"given":"Monday O","family":"Ogese","sequence":"first","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Lister","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Alfirevic","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Kevin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4107-7832","authenticated-orcid":false,"given":"Dean J","family":"Naisbitt","sequence":"additional","affiliation":[{"name":"Department of Molecular & Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool L69 3GE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,27]]},"reference":[{"key":"2021083017304788000_kfab084-B1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/gm350","article-title":"In silico analysis of HLA associations with drug-induced liver injury: Use of a HLA-genotyped DNA archive from healthy volunteers","volume":"4","author":"Alfirevic","year":"2012","journal-title":"Genome Med"},{"key":"2021083017304788000_kfab084-B2","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1021\/acsinfecdis.7b00258","article-title":"Developments in glycopeptide antibiotics","volume":"4","author":"Blaskovich","year":"2018","journal-title":"ACS Infect. 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