Immunologic Tolerance to Allergenic Protein Determinants: Properties of Tolerance Induced in Mice Treated with Conjugates of Protein and a Synthetic Copolymer of D-Glutamic Acid and D-Lysine (D-GL)

Abstract

Conjugates of proteins and the synthetic copolymer of D-glutamic acid and D-lysine (protein-D-GL) reproducibly induce significant unresponsiveness to the protein antigens in experimental mice. Proteins studied include ovalbumin and antigen E of ragweed extract, the major allergen of ragweed pollen. The unresponsive state 1) can be induced in both unsensitized and previously sensitized experimental animals, 2) is selectively confined to responses of the IgE antibody class, 3) is long lasting, and 4) is highly antigen specific. IgE antibody responses can also be suppressed by administering comparable doses of unconjugated protein alone; however, the unresponsive state induced in this manner is only transient and rebound production of IgE antibody is often observed. Results from the studies of the cellular basis of the protein-D-GL induced unresponsiveness demonstrate that 1) protein-D-GL conjugates do not induce unresponsiveness at the level of protein-specific B cells, 2) tolerance is not induced by virtue of a detectable antigen-specific suppressor T cell mechanism, 3) tolerance is most probably induced in the antigen-specific helper T cell populations. The significant IgE-selective and antigen-specific tolerogenic activity of protein-D-GL conjugates make these compounds potential candidates for use as therapeutic agents in the treatment of IgE-mediated human allergic disorders induced by protein allergens.