Host Genetic and Adjuvant Factors Influence Epitope Specificity to a Major Recombinant Grass Allergen

Abstract

The role of host genetic and adjuvant factors in the induction of immune responses to a major recombinant Kentucky bluegrass allergen was examined utilizing five strains of mice and two different adjuvants. Analysis of the recombinant allergen-specific antibodies induced in these strains indicated that the antibodies of various isotypes were differentially regulated. In terms of IgE antibody response, BDF1 and DBA/2 were characterized as high responder, whereas BALB/C, CBA/J and C57BL/6 were intermediate and SJL was a low responder. In different strains, both dextran sulfate (DS) and complete Freund’s adjuvant (CFA), as adjuvants, induced recombinant allergen-specific IgE antibodies of similar titer, however, CFA induced higher IgG2a and lower IgM antibodies compared to DS. Further, analysis of T cell proliferative responses of the splenocytes of different strains demonstrated that these strains varied also in their capacity to respond to synthetic peptides. Furthermore, utilizing a panel of synthetic peptides corresponding to the recombinant allergen, we demonstrated that the antibodies induced by the recombinant allergen with CFA in different strains vary with respect to their epitope specificity. In the BDF1 strain, compared to DS, CFA as adjuvant induced recombinant allergen-specific antibodies of additional peptide specificity. Taken together, these results suggest that both host genetic background and adjuvants govern the fine specificity of antibodies produced against this recombinant Kentucky bluegrass allergen.

Mouse Strain Specificity of the IgE Response to the Major Allergens of <i>Phleum pratense</i>

“…SJL/j mice on the other hand are generally considered to be low IgE responders due to a failure in early IL-4 generation [13]; this low IgE responsiveness in SJL/j mice is not due to a defect in IL-4 production per se, but may be due to an increased IFN-γ production by CD8+ T cells which inhibits class switch and suppresses IgE antibody production in these mice [20]. We could demonstrate that SJL/j mice not only mounted an IgE response but also showed a skin reaction upon intradermal inoculation of pollen extract, which is in contrast to findings by other groups where SJL/j mice were neither found to produce IgE [21]nor exhibited a skin reaction [7]. We suggest that the use of alum in investigations concerning sensitization to the major allergens of P. pratense pollen in mouse models should be well considered, since measurable levels were also obtained in experiments without alum.…”