Recombinant human IgG molecules lacking Fcγ receptor I binding and monocyte triggering activities

摘要: Subclasses of human IgG have a range activity levels with different effector systems but each triggers at least one mechanism cell destruction. We are aiming to engineer non-destructive constant regions for therapeutic applications where depletion cells bearing the target antigen is undesirable. The attributes required lack killing via Fcgamma receptors (R) and complement retention neonatal FcR binding maintain placental transport prolonged half-life IgG. Eight variants were made anti-RhD CD52 specificities. mutations, in or two key CH2 domain, restricted incorporation motifs from other subclasses minimize potential immunogenicity. IgG2 residues positions 233 - 236, substituted into IgG1 IgG4, reduced FcgammaRI by 10(4)-fold eliminated monocyte response antibody-sensitized red blood cells, resulting antibodies which blocked functions active antibodies. If glycine deleted IgG2, was restored IgG4 mutants, low observed. Introduction 327, 330 331 had no effect on caused small decrease triggering.