Je. Allen et al., FINE SPECIFICITY OF THE GENETICALLY CONTROLLED IMMUNE-RESPONSE TO NATIVE AND RECOMBINANT GP15 400 (POLYPROTEIN ALLERGEN) OF BRUGIA-MALAYI/, Infection and immunity, 63(8), 1995, pp. 2892-2898
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.