Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding

Hales, Belinda J.; Hazell, L.A.; Smith, Wendy-Anne; Thomas, Wayne R.

doi:10.1046/j.1365-2745.2002.01500.x

Cited by 54 publications

(58 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of intact intra-chain disulphide bonds in group 2 allergens has been demonstrated [5], as well as lesser effects produced by the substitution of other amino acid residues [5,6]. In addition, rDer p 2 polypeptides with the natural sequence variations [7,8], which vary in different geographical regions [9], show up to twofold differences in IgE binding [10,11,12]. The study of both natural and engineered allergen variants could lead to the development hypoallergens for new types of allergen immunotherapy and to allergen formulations optimised for the mites present in different regions.…”

Section: Introductionmentioning

confidence: 99%

Structural and IgE Binding Analyses of Recombinant Der p 2 Expressed from the Hosts Escherichia coli and Pichia pastoris

Tanyaratsrisakul

Malainual²,

Jirapongsananuruk³

et al. 2009

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: The house dust mite allergen Der p 2 is one of the most important indoor allergens associated with allergic disease. Recombinant Der (rDer) p 2 with high IgE binding activity can be readily produced in Escherichia coli and Pichia pastoris, but the structure and IgE binding of the different methods of preparation have not been compared. Methods: Secondary structure was assessed by circular dichroism (CD). Intrinsic fluorescence and hydrophobic probe (1-anilinonaphthalene 8-sulphonic acid, ANS) were used to study the Der p 2 hydrophobic cavity. IgE binding was assessed by ELISA inhibition. Results: CD analysis showed the expected secondary structure for both nDer p 2 and refolded Der p 2 prepared from E. coli inclusion bodies but primarily random structure for Der p 2 secreted from P. pastoris. The secreted product, however, had disulphide bonding and could be refolded to a similar structure to natural Der (nDer) p 2 after precipitation with trichloro-acetic or ammonium sulphate. ANS binding and intrinsic Trp92 fluorescence showed that all recombinant proteins were different to nDer p 2 and that the allergen secreted from P. pastoris did not form a hydrophobic cavity. Despite the marked structural changes, all preparations of Der p 2 had similar IgE binding to nDer p 2. Conclusion: Despite almost identical IgE binding, rDer p 2 prepared from both E. coli and P. pastoris showed structural differences to nDer p 2. Der p 2 secreted from P. pastoris lacked most of the natural structure, but refolding could induce the natural structure.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural and IgE Binding Analyses of Recombinant Der p 2 Expressed from the Hosts Escherichia coli and Pichia pastoris

Tanyaratsrisakul

Malainual²,

Jirapongsananuruk³

et al. 2009

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…Many important allergens have sequence polymorphisms, as exemplified by mite group 2 allergens [12,13,14] and birch pollen allergen Bet v 1 [15]. The amino acid sequence variations encoded by these polymorphisms could influence IgE-binding reactivity, T-cell response, and cytokine induction [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Sequence Polymorphisms of Major German Cockroach Allergens Bla g 1, Bla g 2, Bla g 4, and Bla g 5

Jeong

Lee

Shin

et al. 2007

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: The allergenicity of allergens could be influenced by amino acid substitutions in B- or T-cell epitope regions. The German cockroach is known to produce potent allergens inducing strong IgE-mediated allergic reactions. This study was performed to investigate sequence variations in major allergens of the German cockroach. Methods: Reverse transcriptase PCR was used to amplify the cDNA sequences encoding major allergens of the German cockroach (Bla g 1, Bla g 2, Bla g 4, and Bla g 5). Results: The deduced amino acid sequences revealed 38 Bla g 1 variants with 1–7 amino acid substitutions (98.6–99.8% identity), 28 Bla g 2 variants with 1–3 substitutions (99.1–99.7%), 27 Bla g 4 variants with 0–32 substitutions (82.4–100%), and 8 Bla g 5 variants with 1–2 substitutions (99.0–99.5%), respectively. Bla g 1 and Bla g 2 showed sporadic amino acid substitutions despite the divergence in their sequences. Bla g 4 exhibited frequent variations, with clusters of substitutions in residues 29–38, 52–80, and 132–155. Sequence variations in Bla g 4 imply the presence of multiple isoforms and isoallergens, which may in turn have various effects on the IgE-binding capacity and T-cell responsiveness. Only 8 variants were found in Bla g 5, with infrequent amino acid changes of one or two residues. Conclusions: Analyses of T-cell and IgE-binding epitope regions would clarify the effect of sequence polymorphisms on allergenicity, which in turn will aid in the design of allergen formulations for diagnosis and immunotherapy for cockroach allergies.

show abstract

“…The ability to distinguish between a limited number of different Der p 2 isoallergens has been shown for IgG mAbs produced in mice (9,10,12) and for human IgE Abs at the level of polyclonal patient sera in ELISA (13,14). Still, the biological mechanism at the level of effector cell activation triggered by interactions between individual IgE Abs and Der p 2 isoallergens is largely unknown.…”

mentioning

confidence: 99%

Isoallergen Variations Contribute to the Overall Complexity of Effector Cell Degranulation: Effect Mediated through Differentiated IgE Affinity

Christensen

Riise

Bang

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

Genetic variation of Der p 2 allergens: effects on T cell responses and immunoglobulin E binding

Cited by 54 publications

References 33 publications

Structural and IgE Binding Analyses of Recombinant Der p 2 Expressed from the Hosts <i>Escherichia coli</i> and <i>Pichia pastoris</i>

Structural and IgE Binding Analyses of Recombinant Der p 2 Expressed from the Hosts <i>Escherichia coli</i> and <i>Pichia pastoris</i>

Sequence Polymorphisms of Major German Cockroach Allergens Bla g 1, Bla g 2, Bla g 4, and Bla g 5

Isoallergen Variations Contribute to the Overall Complexity of Effector Cell Degranulation: Effect Mediated through Differentiated IgE Affinity

Contact Info

Product

Resources

About