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- Title
Gilt required for RTL550-CYS-MOG to treat experimental autoimmune encephalomyelitis.
- Authors
Burrows, Gregory; Meza-Romero, Roberto; Huan, Jianya; Sinha, Sushmita; Mooney, Jeffrey; Vandenbark, Arthur; Offner, Halina
- 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.
- Subjects
T cell receptors; AUTOIMMUNE diseases; ENCEPHALOMYELITIS; ARTHRITIS; CLINICAL trials; MULTIPLE sclerosis
- Publication
Metabolic Brain Disease, 2012, Vol 27, Issue 2, p143
- ISSN
0885-7490
- Publication type
Article
- DOI
10.1007/s11011-012-9289-7