Activation of the TCR complex by small chemical compounds.
Small chemical compounds and certain metal ions can activate T cells, resulting in drug hypersensitivity reactions that are a main problem in pharmacology. Mostly, the drugs generate new antigenic epitopes on peptide-major histocompatibility complex (MHC) molecules that are recognized by the T-cell antigen receptor (TCR). In this review we discuss the molecular mechanisms of how the drugs alter self-peptide-MHC, so that neo-antigens are produced. This includes (1) haptens covalently bound to peptides presented by MHC, (2) metal ions and drugs that non-covalently bridge self-pMHC to the TCR, and (3) drugs that allow self-peptides to be presented by MHCs that otherwise are not presented. We also briefly discuss how a second signal-next to the TCR-that naïve T cells require to become activated is generated in the drug hypersensitivity reactions.
Faculty of Biology, Department of Molecular Immunology, Institute of Biology III, University of Freiburg, Freiburg, Germany.
Christine
C
Louis-Dit-Sully
Wolfgang W A
WW
Schamel
D000818:Animals; D004342:Drug Hypersensitivity / Q000276:immunology; D006241:Haptens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008670:Metals / Q000276:immunology; D009930:Organic Chemicals / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*
D006241:Haptens; D008670:Metals; D009930:Organic Chemicals; D017260:Receptor-CD3 Complex, Antigen, T-Cell