GILT required for RTL550-CYS-MOG to treat experimental autoimmune encephalomyelitis

Gregory G. Burrows, Roberto Meza-Romero, Jianya Huan, Sushmita Sinha, Jeffrey L. Mooney, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

MHC class II-derived recombinant T cell receptor ligands (RTLs) modulate the behavior of pathogenic T cells and can reverse clinical and histological signs of autoimmune disease in experimental autoimmune encephalomyelitis (EAE), experimental autoimmune uveitis (EAU) and collagen-induced arthritis (CIA), and are currently in clinical trials for treatment of multiple sclerosis (MS). To expand the utility of these rationally-designed biologics and explore their mechanism(s) of activity in vivo, we have engineered RTL constructs bearing cysteine-tethered antigenic peptides and demonstrate that the appropriate cysteine-tethered RTLs effectively treat EAE. The data presented here suggests that the mechanism by which antigen-specific tolerance induction by RTLs bearing cysteine-tethered antigenic peptides in vivo involves delivery of RTL/antigen to endosomal compartments for processing and re-presentation by full-length MHC class II, with RTLs bearing cysteine-tethered antigenic peptides requiring gamma-interferon-inducible lysosomal thiol-reductase (GILT) for therapeutic activity.

Original languageEnglish (US)
Pages (from-to)143-149
Number of pages7
JournalMetabolic brain disease
Volume27
Issue number2
DOIs
StatePublished - Jun 2012

Keywords

  • EAE
  • GILT mice
  • MHC class II
  • RTL550-CYS-Mog

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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