C. Brander et al., HETEROGENEOUS T-CELL RESPONSES TO BETA-LACTAM-MODIFIED SELF-STRUCTURES ARE OBSERVED IN PENICILLIN-ALLERGIC INDIVIDUALS, The Journal of immunology, 155(5), 1995, pp. 2670-2678
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.