Defining B cell immunodominance to viruses

被引:196
作者
Angeletti, Davide [1 ]
Gibbs, James S. [1 ]
Angel, Matthew [1 ]
Kosik, Ivan [1 ]
Hickman, Heather D. [1 ]
Frank, Gregory M. [1 ]
Das, Suman R. [1 ,2 ]
Wheatley, Adam K. [3 ]
Prabhakaran, Madhu [3 ]
Leggat, David J. [3 ]
McDermott, Adrian B. [3 ]
Yewdell, Jonathan W. [1 ]
机构
[1] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA
[2] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA
[3] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
关键词
ANTIGENIC SIN RESPONSES; ANTIBODY-RESPONSE; INFLUENZA-VIRUSES; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; HEMAGGLUTININ; INFECTION; GENERATION; MEMORY; MICE;
D O I
10.1038/ni.3680
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:456 / +
页数:10
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