Transient dimers of allergens

Juha Rouvinen (Corresponding Author), Janne Jänis, Marja-Leena Laukkanen, Sirpa Jylhä, Merja Niemi, Tero Päivinen, Soili Mäkinen-Kiljunen, Tari Haahtela, Hans Söderlund, Kristiina Takkinen

Research output: Contribution to journalArticleScientificpeer-review

47 Citations (Scopus)

Abstract

Background

Allergen-mediated cross-linking of IgE antibodies bound to the FcεRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.

Methodology/Principal Findings

An analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.

Conclusions/Significance

The results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.

Original languageEnglish
Article numbere9037
Number of pages9
JournalPLoS ONE
Volume5
Issue number2
DOIs
Publication statusPublished - 2010
MoE publication typeA1 Journal article-refereed

Fingerprint

allergens
Dimers
Allergens
crosslinking
Bos
Allergies
allergenicity
antibodies
dimerization
Dimerization
Antibodies
Histamine Release
immunotherapy
mast cells
histamine
crystal structure
Oligomers
Mast Cells
hypersensitivity
Immunotherapy

Cite this

Rouvinen, J., Jänis, J., Laukkanen, M-L., Jylhä, S., Niemi, M., Päivinen, T., ... Takkinen, K. (2010). Transient dimers of allergens. PLoS ONE, 5(2), [e9037]. https://doi.org/10.1371/journal.pone.0009037
Rouvinen, Juha ; Jänis, Janne ; Laukkanen, Marja-Leena ; Jylhä, Sirpa ; Niemi, Merja ; Päivinen, Tero ; Mäkinen-Kiljunen, Soili ; Haahtela, Tari ; Söderlund, Hans ; Takkinen, Kristiina. / Transient dimers of allergens. In: PLoS ONE. 2010 ; Vol. 5, No. 2.
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Rouvinen, J, Jänis, J, Laukkanen, M-L, Jylhä, S, Niemi, M, Päivinen, T, Mäkinen-Kiljunen, S, Haahtela, T, Söderlund, H & Takkinen, K 2010, 'Transient dimers of allergens', PLoS ONE, vol. 5, no. 2, e9037. https://doi.org/10.1371/journal.pone.0009037

Transient dimers of allergens. / Rouvinen, Juha (Corresponding Author); Jänis, Janne; Laukkanen, Marja-Leena; Jylhä, Sirpa; Niemi, Merja; Päivinen, Tero; Mäkinen-Kiljunen, Soili; Haahtela, Tari; Söderlund, Hans; Takkinen, Kristiina.

In: PLoS ONE, Vol. 5, No. 2, e9037, 2010.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Transient dimers of allergens

AU - Rouvinen, Juha

AU - Jänis, Janne

AU - Laukkanen, Marja-Leena

AU - Jylhä, Sirpa

AU - Niemi, Merja

AU - Päivinen, Tero

AU - Mäkinen-Kiljunen, Soili

AU - Haahtela, Tari

AU - Söderlund, Hans

AU - Takkinen, Kristiina

PY - 2010

Y1 - 2010

N2 - BackgroundAllergen-mediated cross-linking of IgE antibodies bound to the FcεRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.Methodology/Principal FindingsAn analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.Conclusions/SignificanceThe results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.

AB - BackgroundAllergen-mediated cross-linking of IgE antibodies bound to the FcεRI receptors on the mast cell surface is the key feature of the type I allergy. If an allergen is a homodimer, its allergenicity is enhanced because it would only need one type of antibody, instead of two, for cross-linking.Methodology/Principal FindingsAn analysis of 55 crystal structures of allergens showed that 80% of them exist in symmetric dimers or oligomers in crystals. The majority are transient dimers that are formed at high protein concentrations that are reached in cells by colocalization. Native mass spectrometric analysis showed that native allergens do indeed form transient dimers in solution, while hypoallergenic variants of them exist almost solely in the monomeric form. We created a monomeric Bos d 5 allergen and show that it has a reduced capability to induce histamine release.Conclusions/SignificanceThe results suggest that dimerization would be a very common and essential feature for allergens. Thus, the preparation of purely monomeric variants of allergens could open up novel possibilities for specific immunotherapy.

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SN - 1932-6203

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Rouvinen J, Jänis J, Laukkanen M-L, Jylhä S, Niemi M, Päivinen T et al. Transient dimers of allergens. PLoS ONE. 2010;5(2). e9037. https://doi.org/10.1371/journal.pone.0009037