Variable binding affinities for allergen suggest a 'selective competition' among immunoglobulins in atopic and non-atopic humans

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 IgA_1,2 and IgG_1-4 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.