Medical Biotechnology
Mapping of conformational immunoglobbulin E epitopes by using chimeric proteins. A. Four contiguous surface patches of Bet v 1 were grafted onto the low IgE binding homologue, Api g 1 from celery. B. IgE binding to these chimeric allergens was tested with sera from 65 birch pollen allergic patients, which revealed patient-specific patterns of IgE binding to different epitopes. Modified from Gepp et al. J Allergy Clin Immunol 2014, 134, 188-94.
Many forms of inhalant allergy are associated with food allergy due to cross-reactivity between inhalant allergens and homologous food allergens. For instance, about 70% of birch pollen allergic patients show adverse reactions to fruits, nuts and vegetables such as apple, hazelnut, kiwi fruit, stone fruits, celery and many more. However, most patients react to only a limited number of these foods and some patients even do not show any symptoms of food allergy despite being sensitized to the cross-reactive major birch pollen allergen, Bet v 1.
The hypothesis underlying the current FWF-funded project is that the epitope recognition profile of Bet v 1-specific IgE determines the clinical consequences of Bet v 1 sensitization. Thus, we aim to characterize IgE epitopes of Bet v 1 and its homologues from plant foods and compare IgE binding to these epitopes with clinical symptoms in a large sample of well-characterized birch pollen allergic patients.
Moreover, we are also interested in the epitope recognition profile of allergen specific IgE antibodies in primary food allergies, such as peanut allergy.
Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1.
J Allergy Clin Immunol 2022, 149, 1786-94.
[PubMed] [Full Text]
Development of a novel Ara h 2 hypoallergen with no IgE binding or anaphylactogenic activity.
J Allergy Clin Immunol 2020, 145, 229-38.
[PubMed] [Full Text]
IgE, IgG4 and IgA specific to Bet v 1-related food allergens do not predict oral allergy syndrome.
Allergy 2015, 70, 59-66.
[PubMed] [Full Text]
Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy.
J Allergy Clin Immunol 2014, 134, 188-94.
[PubMed] [Full Text]
Structures of representative members of the Bet v 1-like superfamily. A: Birch pollen allergen Bet v 1, Betula verrucosa [PDB:1bv1]; B: STAR-related lipid transport domain of MLN64, Homo sapiens [PDB:1em2]; C: Naphthalene 1,2-dioxygenase, α-chain, C-terminal domain, Pseudomonas putida [PDB:1o7n]; D: Phosphatidylinositol transfer protein alpha, Rattus norvegicus [PDB:1t27]; E: Hypothetical protein NE0264, Nitrosomonas europaea [PDB:1xfs], a member of the AHA1 family; F: Hypothetical protein CC1736, Caulobacter crescentus [PDB:1t17], a member of the polyketide cyclase family; G: Hypothetical protein SMU.440, Streptococcus mutans [PDB:2b79]; H: Hypothetical protein PA1206, Pseudomonas aeruginosa [PDB:2ffs]; I: 2-Oxo-1,2-dihydroquinoline 8-monooxygenase, C-terminal domain, Pseudomonas putida [PDB:1z01], a homotrimeric ring hydroxylase; J: Self-sacrificing resistance protein CalC, Micromonospora echinospora [PDB:1zxf]; K: Hypothetical protein APE2225, Aeropyrum pernix [PDB:2ns9], a member of the CoxG family.Structures were coloured according to secondary structure elements homologous to Bet v 1. Modified from Radauer et al. BMC Evol Biol 2008, 8, 286.
One of the many unresolved problems in allergy research is the question what makes a protein allergenic. Besides examining the behaviour of immune cells or model animals upon contact with allergenic and non-allergenic proteins, the availability of large allergen databases in combination with sequence, structure and protein family data now enables researchers to use sequence and structural analysis to gain new insights and lay the basis for novel experimental approaches.
We aim at answering some of the following questions. What is the distribution of allergenic and non-allergenic proteins within allergen containing protein families? Which sequence-related factors, such as similarity to human homologues, similarity to parasite or bacterial proteins or overall sequence conservation with a protein family, show a connection to allergenicity? Can IgE cross-reactivity between homologous allergens be predicted based on sequence similarity data?
The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands.
BMC Evol Biol 2008, 8, 286.
[PubMed] [Full Text]
Protein famiies that contain the highest numbers of allegens as retrieved from the AllFam database.
In recent years, it became clear that most allergenic proteins can be classified into an astonishingly small number of families. Members of these protein families possess similar structures and, in many cases, also similar biochemical functions. This led to the hypothesis that allergenicity depends on structural or functional characteristics of proteins. In addition, common protein family membership is a prerequisite of IgE and T cell cross-reactivity.
In order to help researchers and clinicians getting an overview of families of allergens and their allergenic members, we developed the AllFam allergen family database, a Web resource that enables the user to get protein family data for a frequently updated set of allergens derived from the WHO/IUIS Allergen Nomenclature Database and AllergenOnline.
Navigating through the Jungle of Allergens: Features and Applications of Allergen Databases.
Int Arch Allergy Immunol 2017, 173, 1-11.
[PubMed] [Full Text]
Allergens are distributed into few protein families and possess a restricted number of biochemical functions.
J Allergy Clin Immunol 2008, 121, 847-52. [PubMed] [Full Text]