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T cell recognition of penicillin G: Structural features determining antigenic specificity

作者:Elisabetta Padovan, Daniela Mauri-Hellweg, Werner J. Pichler, Hans Ulrich Weltzien · 发表于:European Journal of Immunology · 年份:1996 · DOI:10.1002/eji.1830260107 · 被引用次数:124 · 研究领域:Drug-Induced Adverse Reactions、Monoclonal and Polyclonal Antibodies Research、Immune Cell Function and Interaction

Penicillin G (Pen G) and other beta-lactam antibiotics frequently induce allergic reactions constituting typical examples of human immune responses to haptens. In fact, penicillins represent a unique set of haptens with outstanding structural variability on the basis of an identical protein-reactive beta-lactam containing backbone. Although both cellular and humoral responses are involved in drug-induced allergies, little is known about the T cell reactivity to penicillins. To understand which structural features determine antigenic specificity, we isolated a panel of MHC-restricted, Pen G-reactive T cell clones from different penicillin-allergic patients and tested them for their capacity to proliferate in the presence of other penicillin derivatives. We found that the antigenic epitope consists of both the amide-linked side chain, which is different in every member of the penicillin family, as well as the thiazolidine ring common to all penicillin derivatives. We also demonstrated the presence of two different types of penicillin-specific T cells, one dependent, and the other independent of antigen processing by autologous antigen-presenting cells. Our data strongly suggest that penicillins form part of the epitopes contacting the antigen receptors of T cells.