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However, they also possess the ability to form novel antigens, or neoantigens, through haptenation of proteins and can stimulate a range of immune\u2010mediated adverse reactions\u2014collectively known as drug hypersensitivity reactions (DHRs). IgE\u2010mediated reactions towards these neoantigens are well studied; however, IgE\u2010independent reactions are less well understood. These reactions usually manifest in a delayed manner as different forms of cutaneous eruptions or liver injury consistent with priming of an immune response.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    studies have confirmed the infiltration of T cells into the site of inflammation, and the subsets of T cells involved appear dependent on the nature of the reaction. Here, we review the evidence that has led to our current understanding of these immune\u2010mediated reactions, discussing the nature of the lesional T cells, the characterization of drug\u2010responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen processing and presentation pathway to stimulate these deleterious responses. Thus, we highlight the need for a more comprehensive understanding of the underlying genetic and molecular basis of penicillin\u2010induced DHRs.\n                  <\/jats:p>","DOI":"10.1111\/all.14355","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T04:11:51Z","timestamp":1588911111000},"page":"150-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The complexity of T cell\u2013mediated penicillin hypersensitivity reactions"],"prefix":"10.1111","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-6641","authenticated-orcid":false,"given":"Shawn J. R.","family":"Goh","sequence":"first","affiliation":[{"name":"Infection and Immunity Program Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology Monash University Clayton Vic. 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