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Defining B cell immunodominance to viruses

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TLDR
This study shows 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.
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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The human antibody response to influenza A virus infection and vaccination.

TL;DR: The differences between natural infection and vaccination in terms of the antibody responses they induce and how these responses protect against future infection are reviewed.
Journal ArticleDOI

Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance

TL;DR: It is found that two independent methods of slow delivery immunization of rhesus monkeys resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates.
References
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Journal ArticleDOI

The Collaborative Cross, a community resource for the genetic analysis of complex traits

Gary A. Churchill, +113 more
- 01 Nov 2004 - 
TL;DR: The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way the authors approach human health and disease.
Journal ArticleDOI

The antigenic structure of the influenza virus A/PR/8/34 hemagglutinin (H1 subtype).

TL;DR: An operational antigenic map of the hemagglutinin of influenza virus A/PR/8/34 indicates the presence of five immunodominant antigenic regions exhibiting various degrees of operational linkage.
Journal ArticleDOI

The structure and receptor binding properties of the 1918 influenza hemagglutinin.

TL;DR: The crystal structures of the HA from the 1918 virus and two closelyrelated HAs in complex with receptor analogs are determined, explaining how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how the virus was able to spread in the human population.
Journal ArticleDOI

Computational design of proteins targeting the conserved stem region of influenza hemagglutinin.

TL;DR: In this paper, a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule was described, and two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity.
Journal ArticleDOI

Disquisitions on original antigenic sin : i. evidence in man

TL;DR: The basic difference between primary and secondary reactivity rests on the presence of a trapping mechanism that allows anamnestic production of antibody against lower doses of the homologous antigen, thus preventing a standard primary response and allowing manifestations of Original Antigenic Sin.
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