REDUCED IMMUNOGENICITY OF MONOMETHOXYPOLYETHYLENE GLYCOL-MODIFIED LYSOZYME FOR ACTIVATION OF T-CELLS

Chemical modification of proteins with monomethoxypolyethylene glycol (mPEG) will reduce the immunogenicity of proteins. In the present stud y, we evaluated the effect of mPEG modification on the capacity of hen egg-white lysozyme (HEL) to stimulate T cells. Lymph node cells (LNCs ) from mice immunized with HEL or with mPEG-HEL conjugate were culture d with these antigens, then we measured the proliferation and IL-2 pro duction. mPEG-modification lowered the T cell-activating capacity of H EL, both in vitro and in vivo. Neither toxicity, nor antigen non-speci fic immunosuppressive capacity was observed with mPEG-HEL and unconjug ated mPEG. Suppressor cells were unlikely to be generated in the mPEG- HEL-primed LNCs. We next examined the behavior of mPEG-HEL during anti gen processing. The capacity of HEL and mPEG-HEL to be incorporated by live cells was much the same. However, the susceptibility to various proteases, including endosomal/lysosomal enzymes, was significantly de creased by mPEG modification. The increased resistance of mPEG-HEL to proteolytic degradation implied that the conjugate was poorly presente d to T cells, This may be an important factor related to the low immun ogenicity of mPEG modified proteins.