Use of a high-affinity peptide that aborts MHC-restricted cytotoxic T lymphocyte activity against multiple viruses in vitro and virus-induced immunopathologic disease in vivo

Binding of a specific peptide(s) from a Viral protein to major histocompati bility complex (MHC) class I molecules is a critical step in the activation of CD8(+) cytotoxic T lymphocytes (CTLs). Once activated, CTLs can cause l ethal disease in an infected host, for example, by killing virus-containing ependymal and ventricular cells in the central nervous system or viral pro tein-expressing beta cells in the pancreatic islets of Langerhans. Here we describe the usage of a designed (not natural) high-affinity peptide to com pete with viral peptide(s)-MHC binding. This peptide blocks virus-induced C TL-mediated disease both in the CNS and in the pancreatic islets in vivo. F urther, the blocking peptide aborts MHC-restricted killing of target cells by CTLs generated to three separate viruses: lymphocytic choriomeningitis v irus, influenza virus, and simian virus 40. (C) 1999 Academic Press.