The Biological Function of Allergens: Relevant for the Induction of Allergic Diseases?

Bufe, Albrecht

doi:10.1159/000024013

Cited by 40 publications

(31 citation statements)

References 32 publications

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“…The question is probably best posed as follows: What characteristics confer on proteins the ability to induce allergic sensitization? In fact, there is no clear answer to this question, although it would appear that among the important variables are the size of the protein, glycosylation status, biologic function (e.g., enzymatic activity), resistance to proteolytic digestion, overall immunogenicity and the way in which the protein is recognized, internalized, and processed by antigen-presenting cells, and the manner in which peptides are presented to responsive T lymphocytes (Aalberse 2000;Astwood et al 1996;Bredehorst and David 2001;Bufe 1998;Huby et al 2000).…”

Section: Scientific Contextmentioning

confidence: 99%

Assessment of the inherent allergenic potential of proteins in mice.

Kimber

Stone

Dearman

2003

Environ Health Perspect

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There is considerable interest in the design of approaches that will permit the accurate identification and characterization of proteins that have the inherent potential to induce sensitization and cause food allergy. Among the methods used currently as part of such assessments are consideration of structural similarity to, or amino acid sequence homology with, known human allergens; whether there exists immunologic cross-reactivity with known allergens; and measurement of resistance to proteolytic digestion in a simulated gastric fluid. Although such approaches provide information that will contribute to a safety assessment, they do not--either individually or collectively--provide a direct evaluation of the ability of a novel protein to cause allergic sensitization. For this reason, work is in progress to design and evaluate suitable animal models that will provide a more holistic assessment of allergenic potential. In this laboratory, the approach we have taken has been to examine the characteristics of immune responses induced in mice following parenteral (intraperitoneal) exposure to test proteins. The basis of this method is to determine simultaneously the overall immunogenic potential of proteins [measured as a function of immunoglobulin (Ig) G antibody responses] and to compare this with their ability to provoke IgE antibody production, IgE being the antibody that effects allergic sensitization. Although this approach has not yet been evaluated fully, the results available to date suggest that it will be possible to distinguish proteins that have the inherent potential to induce allergic sensitization from those that do not. In this article we summarize progress to date in the context of the scientific background against which such methods are being developed.

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Section: Scientific Contextmentioning

confidence: 99%

Assessment of the inherent allergenic potential of proteins in mice.

Kimber

Stone

Dearman

2003

Environ Health Perspect

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“…Moreover, the same allergen preparation can be used for both in vitro and in vivo tests allowing a direct comparison of the diagnostic results obtained with different methods [45, 46, 47]. Beside diagnostic applications, rAllergens are powerful reagents to study the mechanisms involved in allergic reactions [48]and to study structure-function relationships [49]. The elucidation of the primary structure of allergens has already strongly contributed to our understanding of cross-reactivity among apparently unrelated allergenic sources.…”

Section: Recombinant Allergensmentioning

confidence: 99%

Recombinant Allergens for Skin Testing

Schmid‐Grendelmeier¹,

Crameri²

2001

Int Arch Allergy Immunol

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Skin testing is a basic diagnostic procedure widely used to explore immediate-type reactions to allergen preparations in vivo. Despite their reliability, if standardized extracts are used, skin tests suffer from limited reproducibility due to difficulties in preparing consistently standardized extracts from natural raw material. Starting from allergen-encoding cDNAs, large amounts of highly pure allergens with a high batch-to-batch consistency satisfying the quality requirements of medicinal products manufactured by recombinant DNA technology can be produced. These reagents are expected to be qualitatively superior to the commercially available allergen preparations used for the in vitro and in vivo diagnosis of allergic conditions. In this article the current literature available on skin testing with such recombinant allergens (rAllergens) is reviewed and critically analyzed. To date many different rAllergens of various pollens, moulds, mites, bee venom, latex and celery have been used in skin testing in more than 1,600 allergic and control individuals. Skin prick tests as well as intradermal skin tests with rAllergens prove to be highly specific and safe. The diagnostic sensitivity of single rAllergens is generally lower than those obtained with allergen extracts, but can be considerably increased by using rAllergen panels covering the most important allergenic structures present in a given complex allergenic extract. Moreover, quantitative skin testing with single rAllergens allows interesting insights into correlations between the in vivo and in vitro sensitization to a given allergen. In conclusion, skin testing with rAllergens offers a highly specific and safe additional diagnostic tool to elucidate patient- and disease-specific sensitization patterns which will be needed for the development of patient-tailored immunotherapeutic treatments.

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“…Lol p 5 is further shown to be located in the starch granules of pollen with a possible role in starch mobilization and plant germination [7]. Therefore, the structure, function and allergenicity relationships of group 5 allergens are still under discussion [19, 20]. …”

Section: Introductionmentioning

confidence: 99%

Immunochemical Characterization of Two <i>Pichia pastoris-</i>Derived Recombinant Group 5 <i>Dactylis glomerata</i> Isoallergens

Oort

Heer

Lerouge

et al. 2001

Int Arch Allergy Immunol

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Background: Grass pollen of the Poaceae grasses are known to be highly allergenic. Major allergens from the species Lolium, Phleum, Poa and Holcus have been cloned and expressed as recombinant proteins, but of the important species Dactylis glomerata no recombinants are available. Methods: Dac g 5 was cloned by PCR on the basis of homology with Lol p 5 and expressed in Pichia pastoris. Recombinant Dac g 5 (rDac g 5) was affinity purified and compared to natural Dac g 5 (nDac g 5) by immunoblot, radioallergosorbent test (RAST), RAST inhibition, basophil histamine release assay (HRA), competitive radioimmunoassay (RIA) and sandwich enzyme-linked immunosorbent assay (ELISA). In addition, N-terminal sequencing, concanavalin A (Con A) binding, circular dichroism spectrum measurements and matrix-assisted laser desorption ionization-time of flight mass-spectrometric analysis were performed. Results: Clones were obtained that coded for pro-Dac g 5 and two mature isoforms of Dac g 5; the deduced amino acid sequences of both isoforms differed by 4 amino acids. Both mature isoforms were expressed in Pichia at a concentration of ∼15 mg/l. SDS-PAGE analysis showed that rDac g 5 had an apparent M_r approximately 10 kD above nDac g 5. By mass spectrometry this difference was shown to be around 2.5 kD. Positive Con A staining suggested (O-linked) glycosylation as an explanation for this increase in M_r. Whereas both purified recombinants showed a tendency to dimerize, purified nDac g 5 contained a 12-kD peptide not observed for rDac g 5. RAST, RAST inhibition and HRA showed that the IgE reactivity of rDac g 5 was similar to that of nDac g 5. A small subgroup, however, clearly demonstrated decreased IgE reactivity to rDac g 5.02. Differences in immune reactivity of both isoforms were confirmed by monoclonal antibody (mAb)-based sandwich ELISA. Conclusions: Dac g 5 was successfully cloned and expressed in P. pastoris. Minor differences in primary structure between isoforms influence their immune reactivity.

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The Biological Function of Allergens: Relevant for the Induction of Allergic Diseases?

Cited by 40 publications

References 32 publications

Assessment of the inherent allergenic potential of proteins in mice.

Assessment of the inherent allergenic potential of proteins in mice.

Recombinant Allergens for Skin Testing

Immunochemical Characterization of Two <i>Pichia pastoris-</i>Derived Recombinant Group 5 <i>Dactylis glomerata</i> Isoallergens

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