Trimethoprim Stimulates T-Cells through Metabolism-Dependent and -Independent Pathways

Pathways of drug-specific T-cell stimulation have not been fully defined. The aim of this study was to use T-cell clones from a patient hypersensitive to the drug trimethoprim to characterize the involvement of drug metabolism and processing in antigen presentation and cross-reactivity patterns. The MHC-restricted CD4+ and CD8+ T-cell response was dependent on the presence of antigen-presenting cells, and both processing-dependent and -independent pathways of antigen presentation were detected. Stimulation of certain clones was blocked through inhibition of drug-metabolizing enzyme activity. Trimethoprim clones were additionally stimulated with diaveridine and pyrimethamine but not other closely related structures.