title: Trimethoprim stimulates T-cells through metabolism-dependent and -independent pathways.
abstract: 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.
authors.affiliation: MRC Centre for Drug Safety Science, Department of Pharmacology, University of Liverpool, Sherrington Building, Ashton Street, Liverpool, L69 3GE, England.
authors.forename: Sabah
authors.initials: S
authors.lastname: El-Ghaiesh
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Sanderson
authors.forename: John
authors.initials: J
authors.lastname: Farrell
authors.forename: Sidonie N
authors.initials: SN
authors.lastname: Lavergne
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Syn
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Naisbitt
mesh_terms: D000328:Adult; D000892:Anti-Infective Agents, Urinary / Q000276:immunology* / Q000378:metabolism*; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D002999:Clone Cells; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014295:Trimethoprim / Q000276:immunology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000892:Anti-Infective Agents, Urinary; D014295:Trimethoprim