Oldstone M B, von Herrath M, Lewicki H, Hudrisier D, Whitton J L, Gairin J E
Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California, 92037, USA.
Virology. 1999 Apr 10;256(2):246-57. doi: 10.1006/viro.1998.9593.
Binding of a specific peptide(s) from a viral protein to major histocompatibility complex (MHC) class I molecules is a critical step in the activation of CD8(+) cytotoxic T lymphocytes (CTLs). Once activated, CTLs can cause lethal disease in an infected host, for example, by killing virus-containing ependymal and ventricular cells in the central nervous system or viral protein-expressing beta cells in the pancreatic islets of Langerhans. Here we describe the usage of a designed (not natural) high-affinity peptide to compete with viral peptide(s)-MHC binding. This peptide blocks virus-induced CTL-mediated disease both in the CNS and in the pancreatic islets in vivo. Further, the blocking peptide aborts MHC-restricted killing of target cells by CTLs generated to three separate viruses: lymphocytic choriomeningitis virus, influenza virus, and simian virus 40.
病毒蛋白中的特定肽与主要组织相容性复合体（MHC）I类分子的结合是激活CD8(+)细胞毒性T淋巴细胞（CTL）的关键步骤。一旦被激活，CTL可在受感染宿主中引发致命疾病，例如，通过杀死中枢神经系统中含病毒的室管膜细胞和脑室细胞或胰岛中表达病毒蛋白的β细胞。在此，我们描述了一种设计（非天然）的高亲和力肽用于与病毒肽-MHC结合竞争的用途。该肽在体内可阻断中枢神经系统和胰岛中病毒诱导的CTL介导的疾病。此外，该阻断肽可中止由三种不同病毒（淋巴细胞性脉络丛脑膜炎病毒、流感病毒和猿猴病毒40）产生的CTL对靶细胞的MHC限制性杀伤。
