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

Virology. 1999 Apr 10;256(2):246-57. doi: 10.1006/viro.1998.9593.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • H-2 Antigens / immunology*
  • Histocompatibility Antigen H-2D
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic Choriomeningitis / prevention & control
  • Lymphocytic choriomeningitis virus / immunology
  • Major Histocompatibility Complex / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Orthomyxoviridae / immunology
  • Peptides / immunology*
  • Simian virus 40 / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Proteins / immunology*

Substances

  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Peptides
  • Viral Proteins