Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity

  1. Meghan O Altman
  2. Jack R Bennink
  3. Jonathan W Yewdell  Is a corresponding author
  4. Brantley R Herrin
  1. National Institute of Allergy and Infectious Diseases, United States
  2. Emory University School of Medicine, United States

Abstract

Immunoglobulins (Igs) are a crown jewel of jawed vertebrate evolution. Through recombination and mutation of small numbers of genes, Igs can specifically recognize a vast variety of natural and man-made organic molecules. Jawless vertebrates evolved a parallel system of humoral immunity, which recognizes antigens not with Ig, but with a structurally unrelated receptor called the variable lymphocyte receptor B (VLRB). We exploited the convergent evolution of Ig and VLRB antibodies to investigate if intrinsic chemical features of foreign proteins determine their antigenicity and immunogenicity. Surprisingly, we find lamprey VLRB and mouse Ig responses to influenza A virus are extremely similar. Each focuses ~80% of the response on hemagglutinin, mainly through recognition of the major antigenic sites in the hemagglutinin globular head domain. Our findings predict basic conservation of antibody responses to protein antigens, strongly supporting the use of animal models for understanding human antibody responses to viruses and protein immunogens.

Article and author information

Author details

  1. Meghan O Altman

    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jack R Bennink

    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jonathan W Yewdell

    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, United States
    For correspondence
    jyewdell@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
  4. Brantley R Herrin

    Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Reviewing Editor

  1. Thomas Boehm, Max Planck Institute of Immunobiology and Epigenetics, Germany

Publication history

  1. Received: March 17, 2015
  2. Accepted: August 6, 2015
  3. Accepted Manuscript published: August 7, 2015 (version 1)
  4. Version of Record published: August 28, 2015 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,603
    Page views
  • 533
    Downloads
  • 46
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Meghan O Altman
  2. Jack R Bennink
  3. Jonathan W Yewdell
  4. Brantley R Herrin
(2015)
Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity
eLife 4:e07467.
https://doi.org/10.7554/eLife.07467

Further reading

    1. Immunology and Inflammation
    2. Structural Biology and Molecular Biophysics
    Nathanael A Caveney et al.
    Short Report

    Interleukin 27 (IL-27) is a heterodimeric cytokine that functions to constrain T cell-mediated inflammation and plays an important role in immune homeostasis. Binding of IL-27 to cell surface receptors IL-27Rα and gp130 results in activation of receptor-associated Janus Kinases and nuclear translocation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 transcription factors. Despite the emerging therapeutic importance of this cytokine axis in cancer and autoimmunity, a molecular blueprint of the IL-27 receptor signaling complex, and its relation to other gp130/IL-12 family cytokines, is currently unclear. We used cryogenic-electron microscopy to determine the quaternary structure of IL-27, composed of p28 and Ebi3 subunits, bound to receptors, IL-27Rα and gp130. The resulting 3.47 Å resolution structure revealed a three-site assembly mechanism nucleated by the central p28 subunit of the cytokine. The overall topology and molecular details of this binding are reminiscent of IL-6 but distinct from related heterodimeric cytokines IL-12 and IL-23. These results indicate distinct receptor assembly mechanisms used by heterodimeric cytokines with important consequences for targeted agonism and antagonism of IL-27 signaling.

    1. Developmental Biology
    2. Immunology and Inflammation
    David J Turner et al.
    Short Report Updated

    To identify roles of RNA binding proteins (RBPs) in the differentiation or survival of antibody secreting plasma cells we performed a CRISPR/Cas9 knockout screen of 1213 mouse RBPs for their ability to affect proliferation and/or survival, and the abundance of differentiated CD138 + cells in vitro. We validated the binding partners CSDE1 and STRAP as well as the m6A binding protein YTHDF2 as promoting the accumulation of CD138 + cells in vitro. We validated the EIF3 subunits EIF3K and EIF3L and components of the CCR4-NOT complex as inhibitors of CD138 + cell accumulation in vitro. In chimeric mouse models YTHDF2-deficient plasma cells failed to accumulate.