Deciphering the immune pathomechanism of cutaneous drug reactions

The present peptide fragments to T-cells in the context of MHC molecules. Small chemical compounds are thought to acquire immunogenicity by covalent binding to proteins or peptides. This requires chemical reactivity of the compound or its metabolite. We recently elaborated a new pathway of drug presentation to T-cells, namely that even chemically nonreactive drugs like sulfamethoxazole (SMX) can be recognized in an MHC dependent way by T-cell receptors. This concept of 'noncovalent drug presentation' is based on the finding that glutaraldehyde fixed cells could present chemically nonreactive drugs like sulfamethoxazole or lidocaine; and that the drug binding to MHC-peptide complexes is rather labile, as the drug can be washed away - in contrast to covalently binding drugs. Our data show that drugs can bind in a pharmacological way to immune-receptors like MHC or TCR, and that this labile binding is sufficient to elicit an immune response. This drug-presentation may occur in the skin and lead to different symptoms, dependent on the function of the reactive T-cell.