Immunological Unresponsiveness to Specific Antigenic Determinants in Human G Globulin.

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Abstract
Immunological unresponsiveness to HGG (human gamma globulin) fragments was induced by intravenous administration of 5 mg soluble antigen. Concomitantly the animals (guinea pigs) were sensitized to the intact HGG molecule, by injection of 60 ug protein, in complete Freund''s adjuvant, into the rear footpads. The immunoresponse was followed at weekly intervals by delayed hypersensitivity measures, by PCA (passive cutaneous anaphylaxis) titrations, by gel diffusion precipitin analysis and by radioimmunoelectrophoresis. When either Fab, or Fc fragments were given intravenously, together with an injection of HGG in the footpad, the animal became tolerant to those antigenic determinants represented in the fragments, but was simultaneously sensitized to the other antigenic sites on the molecule. When papain digested HGG (free from undigested material) was administered intravenously, however, antibodies directed against the whole intact molecule, but not against either Fab or Fc fragments, were demonstrable. The animals'' immune mechanism is capable of "subtracting'' those determinants shared by both suppressive and sensitizing antigens from those found in the sensitizing antigen alone.