Modulation of allergen-specific immune responses to the major shrimp allergen, tropomyosin, by specific targeting to scavenger receptors on macrophages

Background: Tropomyosin from shrimp is the major cross-reacting crustacean food allergen. Earlier studies have led to the purification and immunochemi cal characterization of the major IgE binding epitopes of the allergen. Mal eylated proteins are known to be specifically targeted to scavenger recepto rs on macrophage. Since antigens processed and presented by macrophages are known to elicit Th1 type of responses and allergic responses are character ized by polarization towards Th2 phenotype, the possibility of modulation o f allergen-specific immune responses by targeting of tropomyosin to macroph age via scavenger receptor was explored. Methods: The IgG and IgE binding p otential of the native maleylated form of tropomyosin was carried out by EL ISA and immunoblot. The ability of the native and maleylated form of allerg en to induce in vitro proliferation of splenocytes from BALB/C mice immuniz ed with both forms of allergen was tested. The in vitro production of IL-4 and IFN-gamma by splenocytes from mice immunized with the two forms of alle rgen was determined from culture supernatants. The in vivo production of se rum IgG1 and IgG2a antibodies following immunization with native and modifi ed allergens was monitored by ELISA. Results: The maleylated form of tropom yosin was found to have reduced antigenicity and allergenicity as compared to its native counterpart. The modified allergen was, however, found to eli cit a cellular response similar to native tropomyosin in vitro. Analysis of the cytokine profiles showed a modulation from an IL-4-dominant, proallerg ic, Th2 phenotype to an IFN-gamma-dominant, antiallergic, Th1 phenotype tha t could also be correlated to a modulation in the in vivo antibody isotype. Conclusion: The results suggest the possible potential for modulating alle rgic responses in vivo by selective targeting to macrophages. Copyright (C) 2000 S. Karger AG, Basel.