Tolerogenic capacity of poly(ethylene glycol) (PEG)-modified ovalbumins in relation to their immunoreactivity towards anti-ovalbumin antibody

Abstract

Ovalbumin (OVA) was chemically modified with poly(ethylene glycol) (PEG) derivatives: activated PEG₂, 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine and activated PM₁₃, copolymer of poly(oxyethylene) allyl methyl diether and maleic anhydride. Pretreatment of BALB/c mice with PEG₂- or PM₁₃-OVA suppressed the production of both IgG- and IgE-class anti-OVA antibodies induced by subsequent immunizations with unmodified OVA. PEG₂-OVA had higher potency to suppress OVA-specific immune response than PM₁₃-OVA. Although extensive modification (62%) of amino groups in the OVA molecule with activated PEG₂ was required to diminish most of its immunoreactivity towards anti-OVA antibodies, only a low degree of modification (27%) was sufficient to induce tolerogenicity to OVA. Thus, the loss of immunoreactivity of PEG₂-OVA was not prerequisite for its tolerogenic capacity. Moreover, the use of completely denatured PEG₂-OVA immunogen lead to the loss of its ability to induce immune tolerance to native OVA. These observations are discussed in relation to the regulatory mechanism of immune response.