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"Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity.
J Immunol. 1999 Feb 15; 162(4):2406-14.JI

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.

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Authors+Show Affiliations

Schramm G
Biochemische und Molekulare Allergologie, Forschungszentrum Borstel, Germany. gschramm@fz-borstel.de
Kahlert H
No affiliation info available
Suck R
No affiliation info available
Weber B
No affiliation info available
Stüwe HT
No affiliation info available
Müller WD
No affiliation info available
Bufe A
No affiliation info available
Becker WM
No affiliation info available
Schlaak MW
No affiliation info available
Jäger L
No affiliation info available
Cromwell O
No affiliation info available
Fiebig H
No affiliation info available

MeSH

AllergensBinding Sites, AntibodyCell LineClone CellsEpitope MappingGenetic VariationHistamine ReleaseHumansImmunoglobulin EPlant ProteinsPoaceaePollenProtein EngineeringSkin TestsT-Lymphocytes

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9973522

Citation

Schramm, G, et al. ""Allergen Engineering": Variants of the Timothy Grass Pollen Allergen Phl P 5b With Reduced IgE-binding Capacity but Conserved T Cell Reactivity." Journal of Immunology (Baltimore, Md. : 1950), vol. 162, no. 4, 1999, pp. 2406-14.
Schramm G, Kahlert H, Suck R, et al. "Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity. J Immunol. 1999;162(4):2406-14.
Schramm, G., Kahlert, H., Suck, R., Weber, B., Stüwe, H. T., Müller, W. D., Bufe, A., Becker, W. M., Schlaak, M. W., Jäger, L., Cromwell, O., & Fiebig, H. (1999). "Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity. Journal of Immunology (Baltimore, Md. : 1950), 162(4), 2406-14.
Schramm G, et al. "Allergen Engineering": Variants of the Timothy Grass Pollen Allergen Phl P 5b With Reduced IgE-binding Capacity but Conserved T Cell Reactivity. J Immunol. 1999 Feb 15;162(4):2406-14. PubMed PMID: 9973522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - "Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity. AU - Schramm,G, AU - Kahlert,H, AU - Suck,R, AU - Weber,B, AU - Stüwe,H T, AU - Müller,W D, AU - Bufe,A, AU - Becker,W M, AU - Schlaak,M W, AU - Jäger,L, AU - Cromwell,O, AU - Fiebig,H, PY - 1999/2/11/pubmed PY - 1999/2/11/medline PY - 1999/2/11/entrez SP - 2406 EP - 14 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 162 IS - 4 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9973522/"Allergen_engineering":_variants_of_the_timothy_grass_pollen_allergen_Phl_p_5b_with_reduced_IgE_binding_capacity_but_conserved_T_cell_reactivity_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9973522 DB - PRIME DP - Unbound Medicine ER -