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T cell receptor mimic peptides and their potential application in T-cell-mediated disease
1Department of Dermatology, University of Mainz, Mainz, Germany. enk@hautklinik.klinik.uni-mainz.de
Background:
A T cell receptor (TCR) peptide was designed that mimics the intramembranous amino acid sequence of the TCR chain. Prior studies had shown that this mimic peptide would inhibit TCR signaling. This study was designed to investigate the use of this mimic peptide for the treatment of T-cell-mediated skin diseases.
Methods:
Synthesized mimic peptides were first tested for their T-cell-inhibitory effect in proliferation assays. Afterwards, mimic peptides were applied to murine ear skin prior to application of a contact allergen and tested for their inhibitory effect in the model of murine 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 as antigen-presenting cells (APCs). Suppression of the proliferative capacity could be overcome by addition of an anti-CD3 monoclonal antibody. When applied to murine ear skin prior to application of a contact allergen, mimic peptide efficiently blocked ear swelling responses in mice. In humans, application of mimic peptide for the treatment of various diseases resulted in amelioration or even cure in patients suffering from atopic dermatitis, psoriasis or lichen planus.
Conclusions:
TCR mimic peptide efficiently abrogates T-cell-mediated immune responses in mice and man in vitro and in vivo. The potential immunosuppressive effect of the drug is discussed.