Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies.

Antibodies which react with products encoded by the human DR locus precipitate a biomolecular membrane glycoprotein complex with m.w. of 29,000 and 34,000 daltons. Such antibodies are directed against HLA-DR Ia-like antigens found on human B cells and human monocytes and have been shown previously to inhibit a variety of in vitro cellular and humoral immune reactions. We have compared the in vitro effects of such antibodies on two assays of human immunity: antigen-specific proliferation and polyclonal immunoglobulin production. Intact IgG fractions of a rabbit heteroantiserum (anti-P29,34), a human MT-2 locus alloantiserum (Ia 172), and a mouse monoclonal antibody (LB 3.1) markedly inhibited in vitro immune reactivities of human mononuclear cells. Interestingly, F(ab')2 preparations of these antibodies failed to inhibit these in vitro immune responses at the concentrations tested. These data suggest that under certain conditions, Fc domains play a critical role in the inhibitory activity of antibodies to Ia-like molecules.