Cross-reactivity of T cell lines and clones to beta-lactam antibiotics.

• DOI: 10.4049/jimmunol.157.3.1071
• Publication Date: 2022-12-31T11:34:16Z
• Authors: D Mauri-Hellweg; M Zanni; E Frei; F Bettens; C Brander; D Mauri; E Padovan; H U Weltzien; W J Pichler
• Keywords: 0301 basic medicine; Base Sequence; Cephalosporin Resistance; Penicillin Resistance; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Molecular Sequence Data; Penicillins; Cross Reactions; Immunoglobulin E; In Vitro Techniques; beta-Lactams; Anti-Bacterial Agents; 3. Good health; 03 medical and health sciences; Radioallergosorbent Test; Humans

Abstract To clarify on a molecular level the specific T cell response to haptens like penicillin G, we generated T cell lines and clones from penicillin-allergic patients. Two types of beta-lactam reactivity of T cells could be delineated: one group of patients showed a rather restricted specificity, as the penicillin-elicited T cell lines generated from such donors proliferated only to the stimulating penicillin, but not to other beta-lactam antibiotics nor to cephalosporines, even if the side chain was identical. This indicates that the penicilloyl structure together with the side chain was recognized by these T cells. The second group comprised patients with more broadly reactive T cells, as they were restimulated by penicillin G as well as by related penicillins like amoxicillin or ampicillin, but not cephalosporines. This indicates that the penicilloyl structure, a common motif of penicillins, was important for T cell recognition. Clones generated from a broadly reactive patient confirmed this heterogeneity, as either monospecific or broadly specific T cell clones could be identified. This broad or very restricted pattern of T cell reactivity was reflected in the use of TCR Vbeta-chains: while the broadly reactive T cell lines showed a heterogenous TCR usage, the highly restricted T cell lines showed an up-regulation of one TCR Vbeta-chain. Thus, our data suggest that the outgrowth of T cells bearing a certain TCR Vbeta may be a sign of a limited cross-reactivity.