Original Paper

Immunological and Structural Analysis of IgE-Mediated Cross-Reactivity between Manganese Superoxide Dismutases
Sabine Flückiger^a, Leonardo Scapozza^b, Christina Mayer^a, Kurt Blaser^a, Gerd Folkers^b, Reto Crameri<sup>a

a</sup>Swiss Institute of Allergy and Asthma Research (SIAF), Davos, and
^bDepartment of Applied Biosciences, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland

Address of Corresponding Author

Int Arch Allergy Immunol 2002;128:292-303 (DOI: 10.1159/000063862)

  Key Words

• Allergy
• Autoreactivity
• Manganese superoxide dismutase
• Molecular modelling

  Abstract

Background: Allergy results from inappropriate immune responses to normally innocuous proteins. More than 300 IgE-binding proteins have been cloned and shown to cover structurally and functionally heterogeneous protein families including enzymes, backbone and storage proteins as well as proteins with unknown function. Structurally related cross-reactive allergens are involved in the pathogenesis of important clinical syndromes. We found that phylogenetically highly conserved proteins, including human manganese superoxide dismutase (MnSOD), are involved in IgE-mediated autoreactivity. Methods: MnSOD cloned from different phylogenetically distant species were produced as recombinant proteins in Escherichia coli and used to study IgE-mediated cross-reactivity and proliferative responses in peripheral blood mononuclear cells (PBMC) of individuals sensitised to Aspergillus fumigatus MnSOD. Homology models of the three-dimensional structures of MnSOD from A. fumigatus, Drosophila melanogaster and Saccharomyces cerevisiae using the human MnSOD structure refined at 2.2 Å as template were constructed to identify conserved amino acid residues exposed to the solvent. Results: Cross-reactivity between the MnSOD at B and T cell level was demonstrated by inhibition experiments showing shared B cell epitopes and by the capability of the different MnSODs to induce proliferative responses in PBMCs of sensitised individuals. Structural modelling allowed to identify conserved residues exposed to the solvent. The identified residues are scattered over the sequence of the enzyme indicating putative conformational IgE-binding epitopes. Conclusions: The results obtained corroborate molecular mimicry as a plausible mechanism to explain autoreactivity to human MnSOD. Moreover, homology modelling provides a rational tool to identify conserved residues involved in defining cross-reactive B cell epitopes.

Copyright © 2002 S. Karger AG, Basel

  Author Contacts

Correspondence to: Prof. Dr. Reto Crameri
Swiss Institute of Allergy and Asthma Research (SIAF)
Obere Strasse 22
CH-7270 Davos (Switzerland)
Tel. +41 81 410 08 48, Fax +41 81 410 08 40, E-Mail crameri@siaf.unizh.ch

  Article Information

Received: December 13, 2001
Accepted after revision: June 17, 2002
Number of Print Pages : 12
Number of Figures : 5, Number of Tables : 3, Number of References : 52