Humoral and Cell-mediated Autoimmune Reactions to Human Acidic Ribosomal P2 Protein in Individuals Sensitized to Aspergillus fumigatus P2 Protein

Abstract

A panel of cDNAs encoding allergenic proteins was isolated from an Aspergillus fumigatus cDNA library displayed on the surface of filamentous phage. Solid phase–immobilized serum immunoglobulin E (IgE) from A. fumigatus–allergic individuals was used to enrich phage displaying IgE-binding molecules. One of the cDNAs encoded a 11.1-kD protein that was identified as acidic ribosomal phosphoprotein type 2 (P2 protein). The allergen, formally termed rAsp f 8, shares >62% sequence identity and >84% sequence homology to corresponding eukaryotic P2 proteins, including human P2 protein. The sequences encoding human and fungal P2 protein were subcloned, expressed in Escherichia coli as His6-tagged fusion proteins, and purified by Ni2+–chelate affinity chromatography. Both recombinant P2 proteins were recognized by IgE antibodies from allergic individuals sensitized to the A. fumigatus P2 protein and elicited strong type 1–specific skin reactions in these individuals. Moreover, human and fungal P2 proteins induced proliferative responses in peripheral blood mononuclear cells of A. fumigatus– allergic subjects sensitized to the fungal P2 protein. These data provide strong evidence for in vitro and in vivo humoral and cell-mediated autoreactivity to human P2 protein in patients suffering from chronic A. fumigatus allergy.

Cross-Reactivity and 1.4-Å Crystal Structure ofMalassezia sympodialisThioredoxin (Mala s 13), a Member of a New Pan-Allergen Family

“…Cross-reactivity between allergens and closely related homologous human Ags is often observed in allergic individuals suffering from chronic atopic diseases (8 -11) and potentially contribute to exacerbation and/or perpetuation of chronic allergic reactions (6,10). These studies provide strong evidence for in vitro and in vivo humoral and cell-mediated IgE autoreactivity in patients suffering from long-lasting atopic diseases (8,11). Structural studies have shown that the availability of the crystal structure of a given allergen and its human homolog allows a detailed definition of the residues potentially involved in cross-reactivity (12).…”

“…Perhaps the most interesting class of pan-allergens includes environmental allergens sharing structural homology to self-Ags. These structures, including manganese superoxide dismutase, acidic ribosomal P 2 proteins, cyclophilins, and profilins (9,11,12,20,38), have been implicated in exacerbation and/or perpetuation of severe atopic disorders. In contrast to allergenicity, which is an intrinsic property of many different molecular structures, Ab-mediated cross-reactivity among homologous proteins is largely determined by common structural features shared between protein families (13).…”

T Cell Vaccination in Mice with Invasive Pulmonary Aspergillosis

“…However, whether Th2 cells or some regulatory cells, known to mediate some forms of nasal tolerance (67), mediate the effects of Asp f 2 in IPA remains to be determined. The occurrence of autoreactivity in patients suffering from chronic A. fumigatus allergy (39,40) indicates the complexity of the allergic responses to Aspergillus. A number of studies indicate that lung DC play a primary role in surveillance of pathogenic Ags and initiation of a primary immune response in the lung (47,68,69).…”

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

“…This class most likely induces symptoms through molecular mimicry between shared B-and T-cell epitopes present in homologous pairs of molecules (110)(111)(112). Based on the solved crystal structures of the environmental allergens MnSOD, cyclophilin and thioredoxin, reactivity to self-antigens showing sequence homology with environmental allergens can be clearly traced back to conserved amino acid residues clustered on the surface of the IgE-binding molecules.…”