title: Defining B cell immunodominance to viruses.
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.
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Davide
authors.identifier: 0000-0002-5256-1972
authors.initials: D
authors.lastname: Angeletti
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Gibbs
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Angel
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kosik
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Hickman
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Frank
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.|Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Suman R
authors.initials: SR
authors.lastname: Das
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Adam K
authors.identifier: 0000-0002-5593-9387
authors.initials: AK
authors.lastname: Wheatley
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Madhu
authors.initials: M
authors.lastname: Prabhakaran
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Leggat
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Adrian B
authors.initials: AB
authors.lastname: McDermott
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yewdell
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000068617:Genetic Background; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology; D011487:Protein Conformation; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014780:Viruses / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016056:Immunodominant Epitopes