On Intrinsic Allergenicity. Using Lipocalins To Probe The Mechanisms Of Allergy. (37.20)

Abstract

Abstract What makes an antigen an allergen? It seems obvious that IgE-epitopes of allergens are necessary but not sufficient to cause initial sensitization and further to postulate that allergens contain separate molecular motifs that allow interaction with functionally important non-IgE molecules of the key cellular effectors. This way they actively influence development of the hypersensitive phenotype through “intrinsic allergenicity” of the allergen molecules.. We propose that comparative studies of lipocalin allergens, a collection of distinct, but structurally and functionally homologous molecules from different species, may shed light on the property of intrinsic allergenicity. Our overall hypothesis is that xenogeneic lipocalins, via interaction with components of the innate human immune system, such as mast cells, dendritic cells, lymphocytes, or progenitors or secreted mediators of these cells, can promote the afferent and/or the efferent phase of the allergic response, stimulating development of IgE-, rather than IgG-responses to their major immunogenic epitopes. Using human cultured mast cells, we have shown that these cells express the lipocalin receptor megalin, that megalin is massively induced by cultivating the mast cells with monomeric IgE, and. report on further investigations into its role in development of IgE-dependent lipocalin allergy.