Heterogeneous T cell responses to beta-lactam-modified self-structures are observed in penicillin-allergic individuals

Abstract

To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself or penicillin G coupled with human serum albumin (BPO-HSA). T cell clones specific for penicillin G or BPO-HSA were established and their phenotype and reactivity to both forms of the beta-lactam were analyzed. T cell clones stimulated by penicillin G were CD4 and CD8 positive, whereas BPO-HSA stimulated the growth of CD4+ T cells. The penicillin G-specific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G. In contrast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones. In addition to classical APC, activated MHC class II expressing T cells could also restimulate the penicillin G-specific clones, indicating that various cell types might serve as APC. Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokine pattern as most clones produced high amounts of IL-2, IFN-gamma, TFN-alpha, and rather variable levels of IL-4 and IL-5. Since no Ag processing was required, penicillin G may stimulate T cells by binding directly to MHC molecules on the cell surface or to their embedded peptide. Alternatively, it may bind to soluble proteins like HSA, which are processed and subsequently presented in an immunogenic form. These different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy.