The challenge in treating certain immune disorders, such as autoimmune disease and host–graft disease, is to disarm the destructive potential of cytotoxic T lymphocytes (CTL) while avoiding generalized immunosuppression. Jameson and colleagues reasoned that by specifically interfering with protein–protein interactions involved in CTL activation, they could block its harmful effects while avoiding damage to resting cells. They rationally designed about 50 peptide mimetics corresponding to the protein-binding region of the murine CD8 protein, which serves as a scaffold for protein-protein interactions required for T-cell activation. One peptide exhibited dose-dependent inhibition of CD8-dependent CTL activity, without affecting mixed lymphocyte reactions. When administered to mice infected with a murine retrovirus, the peptide selectively inhibited the antiviral CTL response without impinging on the resting repertoire of cells (see p. 984).