Abstract

Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery. Passive antibody transfer and sequential infection experiments demonstrated 'original antigenic suppression', a phenomenon in which antibodies suppress memory responses to the priming antigenic site. Our study provides a template for attaining deeper understanding of antibody ID to viruses and other complex immunogens.

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Acknowledgements

We thank the NIAID Comparative Medicine Branch for maintaining the mice used in this study, and P. Palese and F. Krammer (Icahn School of Medicine at Mount Sinai) for the chimeric HA virus construct. Supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (J.W.Y. and A.B.M.).

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Affiliations

  1. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

    • Davide Angeletti
    • , James S Gibbs
    • , Matthew Angel
    • , Ivan Kosik
    • , Heather D Hickman
    • , Gregory M Frank
    • , Suman R Das
    •  & Jonathan W Yewdell
  2. Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Suman R Das
  3. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

    • Adam K Wheatley
    • , Madhu Prabhakaran
    • , David J Leggat
    •  & Adrian B McDermott

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Contributions

D.A. designed and performed experiments, analyzed data and wrote the paper; J.S.G., M.A., I.K., H.D.H., G.M.F. and S.R.D. designed and performed experiments and analyzed data; A.K.W., M.P., D.J.L. and A.B.M. designed and generated critical reagents for the study; and J.W.Y. designed experiments, analyzed data and wrote the paper. All authors provided useful comments on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jonathan W Yewdell.

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https://doi.org/10.1038/ni.3680

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