DIRECT, MHC-DEPENDENT PRESENTATION OF THE DRUG SULFAMETHOXAZOLE TO HUMAN ALPHA-BETA-T-CELL CLONES

T cells can recognize small molecular compounds like drugs, It is thou ght that covalent binding to MHC bound peptides is required for such a hapten stimulation. Sulfamethoxazole, like most drugs, is not chemica lly reactive per se, but is thought to gain the ability to covalently bind to proteins after intracellular drug metabolism, The purpose of t his study was to investigate how sulfamethoxazole is presented in an i mmunogenic form to sulfamethoxazole-specific T cell clones, The stimul ation of four CD4+ and two CD8(+) sulfamethoxazole-specific T cell clo nes by different antigen-presenting cells (APC) was measured both by p roliferation and cytolytic assays, The MHC restriction was evaluated, first, by inhibition using anti-class I and anti-class II mAb, and sec ond, by the degree of sulfamethoxazole-induced stimulation by partiall y matched APC, Fixation of APC was performed with glutaraldehyde 0.05% . The clones were specific for sulfamethoxazole without cross-reaction to other sulfonamides, The continuous presence of sulfamethoxazole wa s required during the assay period since pulsing of the APC was not su fficient to induce proliferation or cytotoxicity. Stimulation of clone s required the addition of MHC compatible APC, The APC could be fixed without impairing their ability to present sulfamethoxazole. Sulfameth oxazole can be presented in an unstable, but MHC-restricted fashion, w hich is independent of processing. These features are best explained b y a direct, noncovalent binding of sulfamethoxazole to the MHC-peptide complex.