Evidence map›Paper›PMID 26644466›Full record

ArticleThe Journal of biological chemistry2016

Antigenic Determinants of the Bilobal Cockroach Allergen Bla g 2.

Judith A Woodfolk, Jill Glesner, Paul W Wright, Christopher L Kepley, Mi Li, Martin Himly, Lyndsey M Muehling, Alla Gustchina, Alexander Wlodawer, Martin D Chapman and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Design of an Ara h 2 hypoallergen from conformational epitopes.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2024
    Article
  3. Article
  4. Article
  5. Article
  6. Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2.Journal of immunology (Baltimore, Md. : 1950) · 2020
    Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. New Insights into Cockroach Allergens.Current allergy and asthma reports · 2017
    Review
  13. Article
  14. Article
  15. Indoor Allergens and Allergic Respiratory Disease.Current allergy and asthma reports · 2016
    Review
  16. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 2 countries.

Judith A WoodfolkFrom the Allergy Division, Department of Medicine, University of Virginia, Charlottesville, Virginia 22903.
Jill GlesnerINDOOR Biotechnologies, Inc., Charlottesville, Virginia 22908.
Paul W WrightFrom the Allergy Division, Department of Medicine, University of Virginia, Charlottesville, Virginia 22903.
Christopher L Kepleythe Joint School of Nanoscience and Nanoengineering, University of North Carolina, Greensboro, North Carolina 27401.
Mi Lithe Macromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, Basic Science Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, Maryland 21702, and.
Martin Himlythe Department of Molecular Biology, University of Salzburg, 5020 Salzburg, Austria.
Lyndsey M MuehlingFrom the Allergy Division, Department of Medicine, University of Virginia, Charlottesville, Virginia 22903.
Alla Gustchinathe Macromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702.
Alexander Wlodawerthe Macromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702.
Martin D ChapmanINDOOR Biotechnologies, Inc., Charlottesville, Virginia 22908.
Anna PomésINDOOR Biotechnologies, Inc., Charlottesville, Virginia 22908, apomes@inbio.com.
Indoor Biotechnologies (United States) · USUniversity of Virginia · USNational Institutes of Health · USNational Cancer Institute · USUniversity of North Carolina at Greensboro · USUniversity of Salzburg · AT

Funding

Protein StructureZIABC010348 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WLODAWER, ALEXANDER · 2009 to 2025
$27.5M
INTERDISCIPLINARY TRAINING PROGRAM IN IMMUNOLOGYT32AI007496 · NIAID · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Michael G. Brown, Coleen A McNamara · 1995 to 2026
$10.2M
Antigenic determinants of asthma-associated allergens for design of immunotherapy.R01AI077653 · NIAID · INDOOR BIOTECHNOLOGIES · PI MARTIN D. CHAPMAN, Maksymilian Chruszcz · 2009 to 2026
$9.5M
Intramural NIH HHSNIAID NIH HHS R01 AI077653NIAID NIH HHS R01AI077653NIAID NIH HHS R01AI77653-01A2S1NIAID NIH HHS T32 AI007496PHS HHS HHSN26120080001E
6 · The paper itself

Abstract

Bla g 2 is a major indoor cockroach allergen associated with the development of asthma. Antigenic determinants on Bla g 2 were analyzed by mutagenesis based on the structure of the allergen alone and in complex with monoclonal antibodies that interfere with IgE antibody binding. The structural analysis revealed mechanisms of allergen-antibody recognition through cation-π interactions. Single and multiple Bla g 2 mutants were expressed in Pichia pastoris and purified. The triple mutant K132A/K251A/F162Y showed an ∼100-fold reduced capacity to bind IgE, while preserving the native molecular fold, as proven by x-ray crystallography. This mutant was still able to induce mast cell release. T-cell responses were assessed by analyzing Th1/Th2 cytokine production and the CD4(+) T-cell phenotype in peripheral blood mononuclear cell cultures. Although T-cell activating capacity was similar for the KKF mutant and Bla g 2 based on CD25 expression, the KKF mutant was a weaker inducer of the Th2 cytokine IL-13. Furthermore, this mutant induced IL-10 from a non-T-cell source at higher levels that those induced by Bla g 2. Our findings demonstrate that a rational design of site-directed mutagenesis was effective in producing a mutant with only 3 amino acid substitutions that maintained the same fold as wild type Bla g 2. These residues, which were involved in IgE antibody binding, endowed Bla g 2 with a T-cell modulatory capacity. The antigenic analysis of Bla g 2 will be useful for the subsequent development of recombinant allergen vaccines.

Indexed as

AllergensAnimalsAntibodies, MonoclonalAspartic Acid EndopeptidasesAsthmaCD4-Positive T-LymphocytesCockroachesCrystallography, X-RayEpitopes, T-LymphocyteHumansImmunoglobulin EInsect ProteinsMutagenesisMutationPichiaProtein Bindingallergen Bla g 2AllergensAntibodies, MonoclonalAspartic Acid EndopeptidasesEpitopes, T-LymphocyteImmunoglobulin EInsect Proteinsallergenantigenic determinantaspartic proteaseasthmaBla g 2cockroach allergyepitope mappingimmunotherapysite-directed mutagenesisx-ray crystallography

Identifiers

PMID26644466
PMCPMC4732212
OpenAlexW2195092242

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.