{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T20:33:30Z","timestamp":1785443610115,"version":"3.56.0"},"reference-count":58,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000991","name":"Faculty of Medicine, Nursing and Health Sciences, Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000991","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A subset of patients experience immune\u2010mediated hypersensitivity reactions towards \u03b2\u2010lactam antibiotics, with drug\u2010specific T cells implicated as one of the causative factors. The principal mechanism is thought to involve chemical haptenation of self\u2010peptides, resulting in novel peptide drug\u2010adducts that may trigger T cell recognition. Understanding the interactions between the \u03b2\u2010lactam drug, the T cell receptor (TCR) and the peptide\/human leukocyte antigen (pHLA) complex is critical to gain further mechanistic insights into these hypersensitivity reactions. This study aimed to 1) explore the array of haptenated ligands presented by HLA\u2010A*02:01, 2) evaluate the repertoire of T cells involved in penicillin\u2010induced reactions in a hypersensitive patient and 3) determine if a dominant penicillin\u2010specific TCR clonotype recognises haptenated HLA peptides.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      An immunopeptidomics approach was applied to identify benzylpenicillin (BP)\u2010modified peptide ligands within the HLA\u2010A*02:01 ligandome. The drug\u2010reactive TCR repertoire was analysed by single\u2010cell sequencing of CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells expanded in the presence of BP, and the dominant TCR assayed for reactivity in a reporter cell line.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>We report that BP modifies cysteine in preference to lysine residues within the HLA\u2010A*02:01 immunopeptidome. This modification occurs via cysteine\u2010drug conjugate formation, in conjunction with disulphide\u2010mediated peptide modification, which has not previously been considered in the context of drug hypersensitivities. Furthermore, we demonstrate that a BP\u2010specific TCR expanded from a patient reacts towards a reduction\u2010sensitive epitope, consistent with a BP\u2010cysteine adduct disulphide linked to a cysteine residue within the T cell epitope.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides evidence that cysteine\u2010penicillin adducts can be accommodated by HLA ligands with the potential to induce T cell\u2010mediated allergic reactions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70025","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T14:11:58Z","timestamp":1756995118000},"page":"3165-3177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["HLA\u2010A*02:01 Presents Penicillin\u2010Modified Cysteinylated Peptides for T Cell Recognition"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-6641","authenticated-orcid":false,"given":"Shawn J. 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