Imperative role of glycosylation in human MOG-HLA interaction: molecular insights of MOG-Ab associated demyelination

Myelin oligodendrocyte glycoprotein is a transmembrane protein found on the outer lamella of the myelin sheath. The autoimmune attack on the MOG leads to demyelination which differs from normal multiple sclerosis. MOG has three epitope regions MOG(1-22), MOG(35-55), and MOG(92-106) in the extracellular region, and the crucial MOG(35-55) epitope and Human Leukocyte Antigen (HLA) interaction is the initial step for autoantibody generation. To study the effective role of glycosylation in MOG-HLA interaction, we performed molecular dynamics simulations of the complex where HLA interacts with three MOG epitopes both in the absence and presence of glycan. The results projected that the epitope MOG(1-22) is decisive for the HLA interaction in the absence of glycan and HLA interacts with the epitope MOG(35-55) irrespective of glycan existence. The residues Arg9, Arg46, and Arg66 were found to interact strongly with HLA even in the presence of glycan. The glycan increased the flexibility of hMOG and enhanced the interaction of MOG with water molecules.

Automated summary

Myelin oligodendrocyte glycoprotein is a transmembrane protein that, when attacked by autoimmunity, leads to demyelination. The interaction between MOG and HLA, particularly with epitope MOG(1-22), plays a crucial role in autoantibody generation. Glycosylation affects the flexibility of hMOG and enhances its interaction with water molecules.