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 immunochemical characterization of the major IgE binding epitopes of the allergen. Maleylated proteins are known to be specifically targeted to scavenger receptors on macrophage. Since antigens processed and presented by macrophages are known to elicit Th1 type of responses and allergic responses are characterized by polarization towards Th2 phenotype, the possibility of modulation of allergen-specific immune responses by targeting of tropomyosin to macrophage via scavenger receptor was explored.


METHODS
The IgG and IgE binding potential of the native maleylated form of tropomyosin was carried out by ELISA and immunoblot. The ability of the native and maleylated form of allergen to induce in vitro proliferation of splenocytes from BALB/C mice immunized 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 allergen was determined from culture supernatants. The in vivo production of serum IgG1 and IgG2a antibodies following immunization with native and modified allergens was monitored by ELISA.


RESULTS
The maleylated form of tropomyosin was found to have reduced antigenicity and allergenicity as compared to its native counterpart. The modified allergen was, however, found to elicit a cellular response similar to native tropomyosin in vitro. Analysis of the cytokine profiles showed a modulation from an IL-4-dominant, proallergic, Th2 phenotype to an IFN-gamma-dominant, antiallergic, Th1 phenotype that could also be correlated to a modulation in the in vivo antibody isotype.


CONCLUSIONS
The results suggest the possible potential for modulating allergic responses in vivo by selective targeting to macrophages.
Rajagopal
D
D
Department of Biochemistry, Indian Institute of Science, Bangalore, India.
Ganesh
K A
KA
Subba Rao
P V
PV
D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D033364:Decapoda / Q000737:chemistry / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005512:Food Hypersensitivity; D005786:Gene Expression Regulation / Q000276:immunology; D007114:Immunization; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008298:Maleates / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014335:Tropomyosin / Q000737:chemistry / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008298:Maleates; D011971:Receptors, Immunologic; D014335:Tropomyosin; C030272:maleic acid