Mogtag family of protein antigens

The MOGtag family of fusion proteins can be used as protein antigens to induce Experimental Autoimmune Encephalomyelitis (EAE), a model of central nervous system (CNS) autoimmune disease. EAE is often used to study pathological mechanisms of immune-mediated CNS inflammation and demyelination – thought to be the underlying cause of Multiple Sclerosis and other human diseases. EAE is also used in studies of more basic immune mechanisms that are not necessarily related to any specific disease.

EAE is most often induced using short strings of 25-30 amino acids mimicking immunodominant epitopes of myelin proteins. Myelin Oligodendrocyte Glycoprotein (MOG) is a well-characterized myelin protein, and immunization with MOG, or much more commonly the short MOG35-55 peptide, has become the most prevalent version of EAE.

Despite the popularity of MOG35-55 peptide-induced EAE, there are several important advantages to using a larger protein antigen. These include the induction of a more complex and realistic immune response incorporating CD4+ T cell, CD8+ T cell, and B cell recognition of the autoantigen. Further, unlike MHC-restricted short peptides, protein antigens can be used in different strains of mice or even different species.

The main factors limiting the use of protein antigens to induce EAE are the difficulty and the cost in producing antigen in the lab using existing expression systems. Some proteins can be purchased commercially, but they are relatively expensive. We developed the MOGtag family of proteins to overcome these limitations and promote the wider use of protein antigen in the EAE field.

Advantages of the MOGtag expression systems:

• Modern and efficient expression system coupled with codon optimization for production of large amounts of protein from bacterial culture. Compared to older expression systems, more protein can be generated per batch, thus reducing cost and time spent producing antigen.

• Protein can be isolated using standard molecular lab equipment; no specialized protein handling equipment or expertise is required.

• MOG protein itself is very insoluble. The addition of the thioredoxin tag considerably improves solubility and handling.

• If desired, the entire tag sequence can be removed using a TEV protease leaving pure MOG protein (extracellular domain only) without any extra amino acids. As far as we are aware, no other expression system allows for generation of pure MOG protein.