Mutational analysis of amino acid residues involved in IgE-binding to the Malassezia sympodialis allergen Mala s 11
| Autor: | Annika Scheynius, Claudio Rhyner, Margit Schmidt, Catharina Johansson, Andreas G. Glaser, Kurt D. Berndt, Adnane Achour, Daniel Badia Martinez, Monica Vilhelmsson, Arezou Zargari, Reto Crameri |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Allergy Immunology Immunoglobulin E medicine.disease_cause Ige binding Cross-reactivity Peptide Mapping Microbiology Dermatitis Atopic Fungal Proteins Epitopes Allergen medicine Humans Amino acid residue Molecular Biology Binding Sites Malassezia integumentary system biology Sequence Homology Amino Acid Superoxide Dismutase Aspergillus fumigatus Molecular Mimicry Allergens biology.organism_classification medicine.disease Yeast Recombinant Proteins body regions Malassezia sympodialis biology.protein Female Protein Binding |
| Zdroj: | Molecular immunology. 46(2) |
| ISSN: | 0161-5890 |
| Popis: | The yeast Malassezia sympodialis, which is an integral part of the normal cutaneous flora, has been shown to elicit specific IgE- and T-cell reactivity in atopic eczema (AE) patients. The M. sympodialis allergen Mala s 11 has a high degree of amino acid sequence homology to manganese superoxide dismutase (MnSOD) from Homo sapiens (50%) and Aspergillus fumigatus (56%). Humoral and cell-mediated cross-reactivity between MnSOD from H. sapiens and A. fumigatus has been demonstrated. Taken together with the recent finding that human MnSOD (hMnSOD) can act as an autoallergen in AE patients sensitised to M. sympodialis, we hypothesized that cross-reactivity could also occur between hMnSOD and Mala s 11, endogenous hMnSOD thus being capable of stimulating an immune response through molecular mimicry. Herein we demonstrate that recombinant Mala s 11 (rMala s 11) is able to inhibit IgE-binding to recombinant hMnSOD and vice versa, indicating that these two homologues share common IgE-binding epitopes and providing an explanation at a molecular level for the autoreactivity to hMnSOD observed in AE patients sensitised to Mala s 11. Using molecular modelling and mapping of identical amino acids exposed on the surface of both Mala s 11 and hMnSOD we identified four regions each composed of 4-5 residues which are potentially involved in IgE-mediated cross-reactivity. Mutated rMala s 11 molecules were produced in which these residues were altered. Native-like folding was verified by enzymatic activity tests and circular dichroism. The rMala s 11 mutants displayed lower IgE-binding in comparison to wild-type rMala s 11 using plasma from AE patients. In particular, mutation of the residues E29, P30, E122 and K125 lowered the IgE-binding to Mala s 11. The results of this study provide new insights in the molecular basis underlying the cross-reactivity between Mala s 11 and hMnSOD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect