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.
Publication types
-
Research Support, N.I.H., Intramural
MeSH terms
-
Animals
-
Antibodies, Viral / blood
-
Antibodies, Viral / immunology
-
Antigens, Viral / chemistry
-
Antigens, Viral / immunology
-
B-Lymphocytes / immunology*
-
B-Lymphocytes / metabolism*
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
Genetic Background
-
Hemagglutinin Glycoproteins, Influenza Virus / chemistry
-
Hemagglutinin Glycoproteins, Influenza Virus / immunology
-
Host-Pathogen Interactions / genetics
-
Host-Pathogen Interactions / immunology*
-
Immunization
-
Immunodominant Epitopes / chemistry
-
Immunodominant Epitopes / immunology*
-
Immunologic Memory
-
Influenza A virus / immunology
-
Lymph Nodes / immunology
-
Mice
-
Models, Molecular
-
Orthomyxoviridae Infections / genetics
-
Orthomyxoviridae Infections / immunology
-
Protein Conformation
-
Virus Diseases / genetics
-
Virus Diseases / immunology*
-
Virus Diseases / virology
-
Viruses / immunology*
Substances
-
Antibodies, Viral
-
Antigens, Viral
-
Hemagglutinin Glycoproteins, Influenza Virus
-
Immunodominant Epitopes