Karin Pettenburger

A Low Molecular Weight Allergen of White Birch (Betula verrucosa) Is Highly Homologous to Human Profilin

Cloning of allergens has contributed substantially to the understanding of mechanisms in allergic diseases by providing information about the sequence and hence biological functions of allergens. The major birch pollen allergen, Bet v I [Breiteneder H, et al: EMBO J 1989;8:1935-1938] and the white-faced hornet venom allergen (antigen 5) [Si Yun Fang K, et al: Proc. Natl. Acad. Sc. USA 1988;85:895-899] were shown to be highly homologous to pathogenesis-related proteins of plants. In the case of the major allergen of house dust mite, Der p I, homology to proteases was demonstrated. Therefore, the proposed biological function of these IgE-binding proteins might be related to their allergenic potential. In this paper we tentatively identify a ubiquitous family of low molecular weight allergens as profilins. The identification is based on a sequence homology, (b) binding to poly(L-proline), and (c) immunological cross-reactivity. Recombinant birch profilin was purified to homogeneity and showed the same properties as natural profilins.

Distribution of allergens and allergen-coding mRNAs in various tissues of white birch.

The distribution of allergenic proteins was investigated in various tissues of white birch, Betula verrucosa (pollen, leaves and male inflorescences containing immature pollen). In addition, callus and suspension culture cells were investigated for expression of IgE-binding proteins. Furthermore, RNA was extracted from all these tissues and subjected to in vitro translation in a cell-free wheat germ system. Bet v I, the major birch pollen allergen, could be extracted easily from pollen, and in low amounts from callus and leaves. No Bet v I could be extracted from immature male inflorescences. Minor allergens were expressed in high concentrations in pollen and in low concentrations in immature male inflorescences. No minor allergens could be detected in callus and leaves. In contrast to these observations, RNA from all the tissues as well as from callus could be translated in vitro into Bet v I as well as into minor allergens, in particular birch profilin (Bet v II), an important minor allergen. These data suggest that IgE-binding proteins of B. verrucosa, especially Bet v I, under certain circumstances can readily be synthesized in tissues other than pollen. This concept is corroborated by the recent observation that Bet v I reveals high homology with disease resistance response gene products from other plants, suggesting a similar function of Bet v I for the birch.

Similarities of exogenous and endogenous allergens; IgE-autoreactivity in atopic patients

Using serum-IgE from a birch pollen allergic patient we isolated a pollen cDNA encoding for birch profilin. Profilins are ubiquitous cytoskeletal proteins which also participate in the phosphoinositol pathway and in signal transduction. Despite the low degree of sequence homology between plant and mammalian profilins we could demonstrate a distinct IgE-autoreactivity against human profilin in sensitized patients. This phenomenon lead us to investigate the role of autoimmune mechanisms in the maintenance and aggravation of allergic diseases. Endogenous booster mechanisms could be responsible for the elevated anti-birch profilin IgE-titers in sensitized individuals. In addition we demonstrated IgE autoreactivity against a number of human proteins in atopic patients, most pronounced in patients suffering from atopic dermatitis and intrinsic asthma bronchiale suggesting a relevant role of IgE-autoimmunity in the pathogenesis of these diseases.