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 study, 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 cultured with these antigens, then we measured the proliferation and IL-2 production. mPEG-modification lowered the T cell activating capacity of HEL, both in vitro and in vivo. Neither toxicity, nor antigen non-specific immunosuppressive capacity was observed with mPEG-HEL and unconjugated mPEG. Suppressor cells were unlikely to be generated in the mPEG-HEL-primed LNCs. We next examined the behavior of mPEG-HEL during antigen 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 decreased by mPEG modification. The increased resistance of mPEG-HEL to proteolytic degradation implied that the conjugate was poorly presented to T cells. This may be an important factor related to the low immunogenicity of mPEG modified proteins.
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Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ito
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Koga
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Ueda
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Imoto
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D000818:Animals; D002645:Chickens; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009113:Muramidase / Q000187:drug effects / Q000276:immunology*; D010063:Ovum / Q000201:enzymology / Q000276:immunology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*
D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D009113:Muramidase