T cell receptor mimic peptides and their potential application in T-cell-mediated disease

Background: A T cell receptor (TCR) peptide was designed that mimics the in tramembranous amino acid sequence of the TCR chain. Prior studies had shown that this mimic peptide would inhibit TCR signaling. This study was design ed to investigate the use of this mimic peptide for the treatment of T-cell -mediated skin diseases. Methods: Synthesized mimic peptides were first tes ted for their T-cell-inhibitory effect in proliferation assays. Afterwards, mimic peptides were applied to murine ear skin prior to application of a c ontact allergen and tested for their inhibitory effect in the model of muri ne allergic contact sensitivity. The effect of epicutaneous treatment with the peptide was also tested on patients with T-cell-mediated skin disease. Results: Mimic peptide potently inhibited proliferation of CD4+ and CD8+ T cells when added to allogeneic proliferation assays using dendritic cells a s antigen-presenting cells (APCs). Suppression of the proliferative capacit y could be overcome by addition of an anti-CD3 monoclonal antibody. When ap plied to murine ear skin prior to application of a contact allergen, mimic peptide efficiently blocked ear swelling responses in mice. In humans, appl ication of mimic peptide for the treatment of various diseases resulted in amelioration or even cure in patients suffering from atopic dermatitis, pso riasis or lichen planus. Conclusions: TCR mimic peptide efficiently abrogat es T-cell-mediated immune responses in mice and man in vitro and in vivo. T he potential immunosuppressive effect of the drug is discussed. Copyright ( C) 2000 S. Karger AG, Basel.