Related Experiment Video
Updated: Jul 8, 2026
Quantification of Autoreactive Antibodies in Mice upon Experimental Autoimmune Encephalomyelitis
Published on: December 1, 2023
A combined NMR and molecular dynamics simulation study to determine the conformational properties of agonists and
Efthimia D Mantzourani1, Klemen Blokar, Theodore V Tselios
1Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 116 35, Athens, Greece; Department of Chemistry, University of Patras, 265 00, Rion, Patras, Greece.
Abstract:
Myelin basic protein (MBP) is one of the best characterized autoantigens causing multiple sclerosis (MS), via a procedure that involves a stable formation of the trimolecular complex of a T-cell Receptor (TCR), an MBP epitope, and the receptor HLA-DR2b. Experimental autoimmune encephalomyelitis (EAE) is considered as an instructive model for MS in humans, and plenty of X-ray data is available for a number of EAE inducing peptide-receptor complexes. To date, though, there are no data available for complexes involving peptides reversing EAE, namely antagonists. Conformational properties of the EAE inducing epitope MBP(87-99) were analyzed in DMSO using the NOE connectivities and vicinal H(N)-H(alpha) coupling constants, and compared with the antagonist altered peptide ligands. A robust method, which is based on a combination of molecular dynamics and energy minimization, is proposed for identifying the putative bioactive conformations. Generated conformations are compared with the known X-ray structure of MBP(83-96) (human sequence numbering) in the HLA-DR2b complex. The structural motif for the agonist-antagonist activity is discussed.
