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 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.
Oldstone
M B
MB
Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California, 92037, USA.
von Herrath
M
M
Lewicki
H
H
Hudrisier
D
D
Whitton
J L
JL
Gairin
J E
JE
D000208:Acute Disease; D000818:Animals; D006183:H-2 Antigens / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009975:Orthomyxoviridae / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D013539:Simian virus 40 / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides; D014764:Viral Proteins