TY - JOUR
T1 - Single Beta{3}-amino acid substitutions to MOG peptides suppress the development of experimental autoimmune encephalomyelitis
AU - McDonald, Courtney
AU - Payne, Natalie Lisa
AU - Sun, Guizhi
AU - Clayton, Daniel John
AU - Del Borgo, Mark Pasqualino
AU - Aguilar, Marie Isabel
AU - Perlmutter, Patrick
AU - Bernard, Claude Charles Andre
PY - 2014
Y1 - 2014
N2 - CD4+ T-cells play a key role in the pathogenesis of multiple sclerosis (MS). Altered peptide ligands capable of modulating T-cell autoreactivity are considered a promising strategy for development of antigen-specific therapies for MS. Since peptides are inherently unstable, the current study explored single ?-amino acid substitution as a means of stabilizing an epitope of myelin oligodendrocyte glycoprotein. ?-Amino acid substitution at position 44, the major T-cell receptor contact residue, increased the half-life of active metabolites. Vaccination with one altered peptide, MOG44?F, conferred protection from EAE, decreased T-cell autoreactivity and pro-inflammatory cytokine production. Additional studies using MOG44?F in an oral treatment regimen, administered after EAE induction, also attenuated disease severity. Thus, altered peptides such as those reported here may lead to the development of novel and more specific treatments for MS.
AB - CD4+ T-cells play a key role in the pathogenesis of multiple sclerosis (MS). Altered peptide ligands capable of modulating T-cell autoreactivity are considered a promising strategy for development of antigen-specific therapies for MS. Since peptides are inherently unstable, the current study explored single ?-amino acid substitution as a means of stabilizing an epitope of myelin oligodendrocyte glycoprotein. ?-Amino acid substitution at position 44, the major T-cell receptor contact residue, increased the half-life of active metabolites. Vaccination with one altered peptide, MOG44?F, conferred protection from EAE, decreased T-cell autoreactivity and pro-inflammatory cytokine production. Additional studies using MOG44?F in an oral treatment regimen, administered after EAE induction, also attenuated disease severity. Thus, altered peptides such as those reported here may lead to the development of novel and more specific treatments for MS.
UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0165572814009138
U2 - 10.1016/j.jneuroim.2014.09.022
DO - 10.1016/j.jneuroim.2014.09.022
M3 - Article
SN - 0165-5728
VL - 277
SP - 67
EP - 76
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -