Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2

Geoffrey A. Mueller, Jill Glesner, Jacob L. Daniel, Jian Zhang, Noah Hyduke, Crystal M. Richardson, Eugene F. DeRose, Martin D. Chapman, R. Stokes Peebles Jr., Scott A. Smith and Anna Pomés
J Immunol October 15, 2020, 205 (8) 1999-2007; DOI: https://doi.org/10.4049/jimmunol.2000295
Geoffrey A. Mueller
*Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Geoffrey A. Mueller
Jill Glesner
†Basic Research, Indoor Biotechnologies, Inc., Charlottesville, VA 22903;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacob L. Daniel
‡Vanderbilt University Medical Center, Nashville, TN 37232; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jacob L. Daniel
Jian Zhang
‡Vanderbilt University Medical Center, Nashville, TN 37232; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noah Hyduke
§University of South Carolina, Columbia, SC 22908
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Crystal M. Richardson
†Basic Research, Indoor Biotechnologies, Inc., Charlottesville, VA 22903;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Crystal M. Richardson
Eugene F. DeRose
*Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eugene F. DeRose
Martin D. Chapman
†Basic Research, Indoor Biotechnologies, Inc., Charlottesville, VA 22903;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Martin D. Chapman
R. Stokes Peebles Jr.
‡Vanderbilt University Medical Center, Nashville, TN 37232; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for R. Stokes Peebles Jr.
Scott A. Smith
‡Vanderbilt University Medical Center, Nashville, TN 37232; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Scott A. Smith
Anna Pomés
†Basic Research, Indoor Biotechnologies, Inc., Charlottesville, VA 22903;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anna Pomés
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • Four human Der p 2–specific IgE mAbs were identified by a new hybridoma technology.

  • The human IgE mAbs recognize two nonoverlapping epitopes on Der p 2.

  • NMR identified residues in the epitopes of human IgE and murine IgG mAbs.

Abstract

IgE Abs drive the symptoms of allergic disease upon cross-linking allergens on mast cells or basophils. If the IgE binding sites on the allergens could be identified, it may be useful for creating new forms of immunotherapy. However, direct knowledge of the human IgE (hIgE) epitopes is limited because of the very low frequency of IgE-producing B cells in blood. A new hybridoma technology using human B cells from house dust mite–allergic patients was used to identify four Der p 2–specific hIgE mAbs. Their relative binding sites were assessed and compared by immunoassays with three previously studied murine IgG mAbs. Immunoassays showed that the recognition of Der p 2 by the first three hIgE was inhibited by a single murine IgG, but the fourth hIgE recognized a different epitope from all the other mAbs. The functional ability of the hIgE that bind different epitopes to cross-link Der p 2 was demonstrated in a mouse model of passive systemic anaphylaxis. Nuclear magnetic resonance analyses of Der p 2 in complex with IgG and IgE Abs were used to identify specific residues in the epitopes. To our knowledge, the combination of immunoassays to distinguish overlapping epitopes and nuclear magnetic resonance analyses to identify specific residues involved in Ab binding provided the first epitope mapping of hIgE mAbs to an allergen. The technologies developed in this study will be useful in high-resolution mapping of human epitopes on other Ags and the design of improved therapeutics.

Footnotes

  • This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (Project Z01-ES102906 to G.A.M.). This work was supported in part by the NIH, National Institute of Allergy and Infectious Diseases under Award R01AI077653 (to A.P. and M.D.C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    hIgE
    human IgE
    HMQC
    heteronuclear multiple-quantum coherence
    mIgG
    murine IgG
    nDer p 2
    natural Der p 2
    NMR
    nuclear magnetic resonance.

  • Received March 17, 2020.
  • Accepted August 5, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.
View Full Text

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.50

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Log in using your username and password

Forgot your user name or password?
PreviousNext
Back to top

In this issue

The Journal of Immunology: 205 (8)
The Journal of Immunology
Vol. 205, Issue 8
15 Oct 2020
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2
Geoffrey A. Mueller, Jill Glesner, Jacob L. Daniel, Jian Zhang, Noah Hyduke, Crystal M. Richardson, Eugene F. DeRose, Martin D. Chapman, R. Stokes Peebles, Scott A. Smith, Anna Pomés
The Journal of Immunology October 15, 2020, 205 (8) 1999-2007; DOI: 10.4049/jimmunol.2000295

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Mapping Human Monoclonal IgE Epitopes on the Major Dust Mite Allergen Der p 2
Geoffrey A. Mueller, Jill Glesner, Jacob L. Daniel, Jian Zhang, Noah Hyduke, Crystal M. Richardson, Eugene F. DeRose, Martin D. Chapman, R. Stokes Peebles, Scott A. Smith, Anna Pomés
The Journal of Immunology October 15, 2020, 205 (8) 1999-2007; DOI: 10.4049/jimmunol.2000295
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosures
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • A Critical Role for Na+/H+ Exchanger Regulatory Factor 1 in Modulating FcεRI-Mediated Mast Cell Activation
  • PRMT1 Modulates Processing of Asthma-Related Primary MicroRNAs (Pri-miRNAs) into Mature miRNAs in Lung Epithelial Cells
  • A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells
Show more ALLERGY AND OTHER HYPERSENSITIVITIES

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • Public Access
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2021 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606