Fine specificity of the genetically controlled immune response to native and recombinant gp15/400 (polyprotein allergen) of Brugia malayi

Abstract

Polyprotein allergens are a family of structurally homologous molecules from parasitic nematodes which induce specific immunoglobulin E in infected individuals. We show here that both H-2 and non-H-2 factors determine the ability of mice to generate T-and B-cell responses to the filarial polyprotein allergen (Brugia malayi gp15/400). Further, H-2 and non-H-2 genes can complement one another to overcome nonresponsiveness to this molecule. However, these genetic restrictions govern only responses to the native glycoprotein and all strains of mice respond equivalently when immunized with a recombinant polypeptide. Overlapping fragments of gp15/400 were constructed to compare the T-cell and antibody responses to native versus recombinant gp15/400 in responder (BALB/c H-2 d) and nonresponder (B10.D2 H-2 d , CBA H-2 k , and BALB.K H-2 k) strains. BALB/c mice generated T-cell responses to the same fragment (positions 89 to 133 and 1 to 21) whether immunized with native or recombinant material, although the antibody responses differed in fine specificity. H-2 k mice, unresponsive to the native molecule, generated T cells responsive to the centrally located peptide (positions 57 to 100) only when immunized with the recombinant. Antibody responses in H-2 k mice were directed at the peptide (positions 11 to 67) which is glycosylated in the native molecule. Our findings suggest that recognition of gp15/400 is affected by modifications that occur in the parasite but are absent when the molecule is produced in bacteria. This study provides a detailed evaluation of the immune response to an important nematode antigen as a start to the unraveling of the complex interaction of these multicellular parasites with mammalian hosts.

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

“…Other protein modifications, especially glycosylation, are likely to have a major bearing on the immunological response to filarial antigens. For example, certain strains of mice are unable to recognize Bm-NPA-1 (gp15/400) or Bm-GPX-1 (gp29) in their native, glycosylated state (124); however, immunization with nonglycosylated bacterially expressed forms of these antigens restores responsiveness to`nonresponder' strains (30,125). Although glycosylation per se was not shown to be responsible for these observations, this work illustrated that post-translational modifications of products may profoundly influence the immune response to individual filarial antigens.…”

Immune response to Anisakis simplex and other ascarid nematodes

“…Homologues of this protein have now been found widely among nematode parasites, and there is a considerable amount of detail now known about the immune responses they provoke, their biochemical function, and the unusual means by which nematodes synthesize them. There is strong MHC‐restricted genetic control of the antibody response to these proteins in both intestinal and tissue‐parasitic nematode infections ( 42, 46, 55), and this extends to clear‐cut MHC control of IgE responses to ABA‐1 ( 48). The proteins are produced as polyproteins which are post‐translationally cleaved into multiple copies of the approximately 15‐kDa ABA‐1‐like proteins.…”

Comparative Analysis of Glycosylated and Nonglycosylated Filarial Homologues of the 20-Kilodalton Retinol Binding Protein fromOnchocerca volvulus(Ov20)

“…Serological responses in mice exposed to live parasites or recombinant proteins. We have previously done extensive analysis of immune responses in mice implanted with B. malayi (1,19,20). This provided the necessary reagents for analysis of serum reactivity to Bm20.…”

“…Serological responses of human filarial sera. In B. malayi, a 15-kDa retinol and lipid binding polyprotein allergen (gp15/ 400) which is immunodominant in elephantiasis has been characterized (1,14,23). One of the objectives of this report was to establish whether Bm20 was an immunogen in human filarial infection.…”