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

• Type of Material: Article
• Authors: Meghan O Altman, National Institute of Allergy and Infectious Diseases; Jack R Bennink, National Institute of Allergy and Infectious Diseases; Jonathan W Yewdell, National Institute of Allergy and Infectious Diseases; Brantley Herrin, Emory University
• Language: English
• Date: 2015-03-17
• Publisher: eLife Sciences Publications
• Publication Version: Final Published Version
• Copyright Statement: his 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.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.07467
• Title of Journal or Parent Work: eLife
• ISSN: 2050-084X
• Volume: 4
• Grant/Funding Information: The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.; This paper was supported by the following grants:http://dx.doi.org/10.13039/100006492 Division of Intramural Research, National Institute of Allergy and Infectious Diseases to Meghan O Altman, Jack R Bennink, Jonathan W Yewdell. http://dx.doi.org/10.13039/100000002 National Institutes of Health R01 AI072435 to Brantley R Herrin. http://dx.doi.org/10.13039/100008065 Georgia Research Alliance R01 GM100151 to Brantley R Herrin.
• Keywords: influenza; microbiology; antibodies; lamprey; immunodominance; antigenicity; hemagglutinin; immunology; infectious disease; mouse
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

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 (Abs) 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 (HA), mainly through recognition of the major antigenic sites in the HA globular head domain. Our findings predict basic conservation of Ab responses to protein antigens, strongly supporting the use of animal models for understanding human Ab responses to viruses and protein immunogens.