The molecular weight ratio of monomethoxypolyethylene glycol (mPEG) to protein determines the immunotolerogenicity of mPEG proteins

Immunotolerogenic activity of monomethoxypolyethylene glycol- (mPEG) conjugated proteins is a beneficial property in protein pharmaceutics. However, procedures for the preparation of tolerogenic mPEG proteins have not yet been defined. We prepared mPEG proteins with different mPEG contents using three proteins, hen egg lysozyme, ovalbumin and bovine gamma globulin, and their tolerogenicities to antigen-specific T and B cell responses were examined. We found the most appropriate ratio of tolerance induction to be 1.5-2.0, which is the molecular weight ratio of conjugated total mPEGs to protein. This value may assist in the preparation of tolerogenic mPEG proteins.