Atopy is a persistent, aberrant humoral response to certain classes of proteins (allergens) characterized by the presence of allergen-specific IgE. Yet, in both atopic and non-atopic individuals, allergen-specific responses involving the IgA and IgG subclasses have been observed, which evidence does not support models suggesting inherited differences in sensitivity to certain protein classes. Using the major ragweed component Amb a 1 as a model allergen, we assessed the humoral responses in three groups of unrelated donors: (A) atopic, ragweed sensitive; (B) atopic, but not ragweed sensitive; (C) non-atopic. As expected, Amb a 1-specific IgE was present in group A only. However, there were essentially no differences in the relative proportions of Amb a 1-specific IgA1,2 and IgG1-4 among the groups. We also determined the Amb a 1 binding affinities for IgG1 and IgG4 in the three groups, and compared these to Amb a 1-specific IgE binding affinities in group A. Group A donors' Amb a 1-IgE had extremely high affinities (108 to 1011M-1), but their Amb a 1-IgG1 and Amb a 1-IgG4 affinities were significantly lower (107 to 1010M-1). The average IgG4 binding affinities in groups B and C were slightly higher than that of IgG4 in group A, although not statistically significant. However, the IgG1 affinity for Amb a 1 among group C, non-atopic donors was significantly elevated and comparable to the IgE affinity observed in group A, ragweed atopics. Inhibition studies with allergen-specific IgE-free serum showed that all isotypes recognized the major epitopes seen by IgE. These results suggest that there may be a "selective competition" among isotypes for allergens that is driven by the ability to produce high affinity, allergen-specific immunoglobulins.
Bibliographical noteFunding Information:
This work was supported by the Asthma and Allergy Research fund of The Asthma and Allergy Center, University of Minnesota, Minneapolis, MN. The luminometer was purchased with funds from Grant SMF-2096-00 from the Minnesota Medical Foundation, University of Minnesota to M. Blumenthal. Additional support was given to M. Blumenthal by the Minnesota Medical Foundation with funds provided by Mrs. Patricia Maas and Mrs. Shannon Read.
- Amb a 1