FINE SPECIFICITY OF THE GENETICALLY CONTROLLED IMMUNE-RESPONSE TO NATIVE AND RECOMBINANT GP15 400 (POLYPROTEIN ALLERGEN) OF BRUGIA-MALAYI/

Polyprotein allergens are a family of structurally homologous molecule s from parasitic nematodes which induce specific immunoglobulin E in i nfected individuals. We show here that both H-2 and non-H-2 factors de termine 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 nonresponsive ness 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. Overlappin g fragments of gp15/400 were constructed to compare the T-cell and ant ibody responses to native versus recombinant gp15/400 in responder (BA LB/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 fra gment (positions 89 to 133 and 1 to 21) whether immunized with native or recombinant material, although the antibody responses differed in f ine specificity. H-2(k) mice, unresponsive to the native molecule, gen erated T cells responsive to the centrally located peptide (positions 57 to 100) only when immunized with the recombinant. Antibody response s in H-2(k) mice were directed at the peptide (positions 11 to 67) whi ch is glycosylated in the native molecule. Our findings suggest that r ecognition of gp15/400 is affected by modifications that occur in the parasite but are absent when the molecule is produced in bacteria. Thi s study provides a detailed evaluation of the immune response to an im portant nematode antigen as a start to the unraveling of the complex i nteraction of these multicellular parasites with mammalian hosts.