SUPPRESSION OF IMMUNE-RESPONSE TO LOL-P-I BY ADMINISTRATION OF IDIOTYPE

Background: Allergic diseases are characterized by an increased production of specific IgE antibodies. Suppression of IgE antibody production may be accomplished through idiotypic manipulation. Objective: Using an animal model, we explored the effects of anti-Lol p I monoclonal antibody administration on the subsequent IgE and IgG antibody response against Lol p I. Methods: Mice were treated with an anti-Lol p I monoclonal antibody (290A-167), which resulted in the production of anti-idiotypic antibodies as evidenced by their ability to bind to the Fab fraction of 290A-167 and to inhibit the binding of rabbit polyclonal anti-idiotypic antibodies to 290A-167. The animals were then immunized with Lol p I absorbed onto alum, and the immune response to the protein was analyzed. Results: Antigen-specific IgG(1) and IgE responses were strongly suppressed as determined by immunoassay. Suppression of anti-Lol p I IgE antibodies was confirmed by a reduction of end-point titers measured by passive cutaneous anaphylaxis. The suppression of antigen-specific antibody was accompanied by a reduction of anti-Lol p I antibody-producing spleen cells. Conclusion: These data indicate that pretreatment with 290A-167 can strongly downregulate the IgE response to the main allergen of ryegrass pollen, which is associated with an increase in anti-idiotypic antibodies. This approach could provide rapid, long-term hyposensitization in patients with grass pollen allergy.