HETEROGENEOUS T-CELL RESPONSES TO BETA-LACTAM-MODIFIED SELF-STRUCTURES ARE OBSERVED IN PENICILLIN-ALLERGIC INDIVIDUALS

To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself o r penicillin G coupled to human serum albumin (BPO-HSA). T cell clones specific for penicillin G or BPO-HSA were established and their pheno type and reactivity to both forms of the beta-lactam were analyzed. T cell clones stimulated by penicillin G were CD4 or CD8 positive, where as BPO-HSA stimulated the growth of CD4(+) T cells. The penicillin G-s pecific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G. In con trast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones. In addition to classical APC, activated MHC class II e xpressing T cells could also restimulate the penicillin G-specific clo nes, indicating that various cell types might serve as APC. Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokin e pattern as most clones produced high amounts of IL-2, IFN-gamma, TNF -alpha, and rather variable levels of IL-4 and IL-5. Since no Ag proce ssing was required, penicillin G may stimulate T cells by binding dire ctly to MHC molecules on the cell surface or to their embedded peptide . Alternatively, it may bind to soluble proteins like HSA, which are p rocessed and subsequently presented in an immunogenic form. These diff erent modes of presentation, which elicit a variety of immunological r eactivities, may explain the great heterogeneity of the clinical pictu res seen in penicillin allergy.