{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T19:18:01Z","timestamp":1767899881977,"version":"3.49.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Allergy"],"abstract":"<jats:sec><jats:title>Rationale<\/jats:title><jats:p>\u03b2-lactam antibiotics cause drug hypersensitivity reactions (DHR) with various clinical pictures from minor affections like maculopapular exanthema (MPE) and urticaria to severe cutaneous adverse reactions and anaphylaxis. Currently, two different reactivity patterns have been shown to initiate an immune reaction by activating T cells\u2014the hapten concept and the pharmacological interaction with immune receptor (p\u2013i) concept.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>In this study, the relationship between the reactivity pattern of drug-reacting T cells of drug allergic patients and their clinical picture has been investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Drug-reacting T-cell clones (TCCs) were isolated from patients hypersensitive to \u03b2-lactams. Analysis of their reactivity pattern revealed an exclusive use of the hapten mechanism for patients with immediate reactions and for patients of MPE. In patients suffering from drug reactions with eosinophils and systemic symptoms, a severe DHR, analysis of isolated drug-reacting TCC identified the p\u2013i concept as the unique mechanism for T-cell activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results show a shift from hapten pattern in mild allergic reactions to p\u2013i pattern in severe life-threatening allergic reactions. They strongly argue against the current preclinical risk evaluation of new drugs based on the ability to form haptens.<\/jats:p><\/jats:sec>","DOI":"10.3389\/falgy.2022.804605","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T04:29:40Z","timestamp":1645417780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The Activation Pattern of Drug-Reacting T Cells Has an Impact on the Clinical Picture of Hypersensitivity Reactions"],"prefix":"10.3389","volume":"3","author":[{"given":"Natascha","family":"Wuillemin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Ballmer-Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Schlapbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"J\u00f6rg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Yerly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1097\/ACI.0000000000000458","article-title":"Mechanisms leading to T-cell activation in drug hypersensitivity","volume":"18","author":"Meng","year":"2018","journal-title":"Curr Opin Allergy Clin Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1046\/j.1365-2222.2000.00847.x","article-title":"Infiltration of cytotoxic T cells in drug-induced cutaneous eruptions","volume":"30","author":"Yawalkar","year":"2000","journal-title":"Clin Exp Allergy."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2237","DOI":"10.1038\/jid.2015.165","article-title":"Oxypurinol-specific T cells possess preferential TCR clonotypes and express granulysin in allopurinol-induced severe cutaneous adverse reactions","volume":"135","author":"Chung","year":"2015","journal-title":"J Invest Dermatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1016\/j.ajpath.2014.02.018","article-title":"T cells infiltrate the liver and kill hepatocytes in HLA-B(*)57:01-associated floxacillin-induced liver injury","volume":"184","author":"Wuillemin","year":"2014","journal-title":"Am J Pathol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1002\/eji.201142159","article-title":"Avidity determines T-cell reactivity in abacavir hypersensitivity","volume":"42","author":"Adam","year":"2012","journal-title":"Eur J Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s11882-003-0006-9","article-title":"Immunopharmacology of hypersensitivity reactions to drugs","volume":"3","author":"Naisbitt","year":"2003","journal-title":"Curr Allergy Asthma Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1124\/jpet.111.190900","article-title":"Characterization of the antigen specificity of T-cell clones from piperacillin-hypersensitive patients with cystic fibrosis","volume":"341","author":"El-Ghaiesh","year":"2011","journal-title":"J Pharmacol Exp Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1084\/jem.114.6.875","article-title":"Studies on the mechanism of the formation of the penicillin antigen. III The N-(D-alpha-benzylpenicilloyl) group as an antigenic determinant responsible for hypersensitivity to penicillin G","volume":"114","author":"Levine","year":"1961","journal-title":"J Exp Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4956","DOI":"10.4049\/jimmunol.1202949","article-title":"Haplotype determines hapten or p-i T cell reactivity to flucloxacillin","volume":"190","author":"Wuillemin","year":"2013","journal-title":"J Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1016\/j.jaci.2007.02.007","article-title":"Cross-reactivity patterns of T cells specific for iodinated contrast media","volume":"119","author":"Lerch","year":"2007","journal-title":"J Allergy Clin Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2984","DOI":"10.4049\/jimmunol.1302306","article-title":"Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01","volume":"192","author":"Yun","year":"2014","journal-title":"J Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1111\/all.13087","article-title":"Detection of drug-responsive B lymphocytes and antidrug IgG in patients with beta-lactam hypersensitivity","volume":"72","author":"Amali","year":"2017","journal-title":"Allergy."},{"key":"B13","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.jaci.2006.12.617","article-title":"Generation and characterization of antigen-specific CD4+, CD8+, and CD4+CD8+ T-cell clones from patients with carbamazepine hypersensitivity","volume":"119","author":"Wu","year":"2007","journal-title":"J Allergy Clin Immunol."}],"container-title":["Frontiers in Allergy"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/falgy.2022.804605\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T04:29:43Z","timestamp":1645417783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/falgy.2022.804605\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,21]]},"references-count":13,"alternative-id":["10.3389\/falgy.2022.804605"],"URL":"https:\/\/doi.org\/10.3389\/falgy.2022.804605","relation":{},"ISSN":["2673-6101"],"issn-type":[{"value":"2673-6101","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,21]]},"article-number":"804605"}}