DOI: 10.4049/jimmunol.162.4.2406. “Allergen Engineering”: Variants of the Timothy Grass Pollen Allergen Phl p 5b with Reduced IgE-Binding Capacity but Conserved T Cell Reactivity

“Allergen Engineering”: Variants of the Timothy Grass Pollen Allergen Phl p 5b with Reduced IgE-Binding Capacity but Conserved T Cell Reactivity

10.4049/jimmunol.162.4.2406

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract One problem of conventional allergen-specific immunotherapy is the risk of anaphylactic reactions. A new approach to make immunotherapy safer and more efficient might be the application of engineered allergens with reduced IgE-binding capacity but retained T cell reactivity. Using overlapping dodeca-peptides, the dominant T cell epitopes of the timothy grass pollen allergen Phl p 5b were identified. By site-directed mutagenesis outside these regions, point and deletion mutants were generated. Allergen variants were analyzed for IgE-binding capacity with sera of different grass pollen allergic patients by Western blotting, Dot blotting, and EAST inhibition test, and for histamine releasing capacity with peripheral blood basophils from different patients. The deletion mutants revealed significantly reduced IgE reactivity and histamine releasing capacity, compared with the wild-type Phl p 5b. Furthermore, in vivo skin prick tests showed that the deletion mutants had a significantly lower potency to induce cutaneous reactions than the wild-type Phl p 5b. On the other hand, T cell clones and T cell lines from different allergic patients showed comparable proliferation after stimulation with allergen variants and wild-type Phl p 5b. Considering their reduced anaphylactogenic potential together with their conserved T cell reactivity, the engineered allergens could be important tools for efficient and safe allergen-specific immunotherapy.

Bibliography

Schramm, G., Kahlert, H., Suck, R., Weber, B., StuÌwe, H.-T., MuÌller, W.-D., Bufe, A., Becker, W.-M., Schlaak, M. W., JaÌger, L., Cromwell, O., & Fiebig, H. (1999). âAllergen Engineeringâ: Variants of the Timothy Grass Pollen Allergen Phl p 5b with Reduced IgE-Binding Capacity but Conserved T Cell Reactivity. The Journal of Immunology, 162(4), 2406â2414.

Authors 12

Gabriele Schramm (first)
Helga Kahlert (additional)
Roland Suck (additional)
Bernhard Weber (additional)
Hans-Thomas Stüwe (additional)
Wolf-Dieter Müller (additional)
Albrecht Bufe (additional)
Wolf-Meinhard Becker (additional)
Max W. Schlaak (additional)
Lothar Jäger (additional)
Oliver Cromwell (additional)
Helmut Fiebig (additional)

References 34 Referenced 75

Dates

Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 7:47 p.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:34 p.m.)
Indexed	8 months ago (Jan. 3, 2025, 12:30 a.m.)
Issued	26 years, 6 months ago (Feb. 15, 1999)
Published	26 years, 6 months ago (Feb. 15, 1999)
Published Print	26 years, 6 months ago (Feb. 15, 1999)

Funders 0

None

BibTeX

@article{Schramm_1999, title={“Allergen Engineering”: Variants of the Timothy Grass Pollen Allergen Phl p 5b with Reduced IgE-Binding Capacity but Conserved T Cell Reactivity}, volume={162}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.162.4.2406}, DOI={10.4049/jimmunol.162.4.2406}, number={4}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Schramm, Gabriele and Kahlert, Helga and Suck, Roland and Weber, Bernhard and Stüwe, Hans-Thomas and Müller, Wolf-Dieter and Bufe, Albrecht and Becker, Wolf-Meinhard and Schlaak, Max W. and Jäger, Lothar and Cromwell, Oliver and Fiebig, Helmut}, year={1999}, month=feb, pages={2406–2414} }

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