Suppression of human anti-mouse idiotypic antibody responses in hu-PBL-SCID mice.

Severe combined immunodeficient (SCID) mice were engrafted with appropriate numbers of T cells and B plus mononuclear cells, which had been fractionated from normal human peripheral blood leukocytes (hu-PBLs). Treatment of these hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and an anti-ovalbumin, IgG1 murine monoclonal antibody, Mab-2, suppressed the human anti-mouse antibody responses to both the common (gamma 1,kappa) and the idiotypic determinants of Mab-2. Moreover, the Mab-2(mPEG)36 conjugate suppressed the immune responses of hu-PBL-SCID mice to the common and idiotypic determinants of murine monoclonal antibodies to the 2,4-dinitrophenyl residue and to human CD4, consisting also of gamma 1 and kappa chains. It is concluded that a tolerogenic mPEG conjugate of a murine monoclonal antibody induces pan-suppression of the human lymphoid system with respect to other murine monoclonal antibodies that share the isotypic determinants of the original one (here, Mab-2) incorporated in the conjugate. Hence, it may be anticipated that human anti-mouse antibody responses to any murine IgG monoclonal antibody would be suppressed by one of eight mPEG conjugates, each incorporating one of the four subclasses of IgG and one of the two light chains.