Structural biology of antibody:antigen complexes

抗体的结构生物学:抗原复合物

基本信息

  • 批准号:
    8329266
  • 负责人:
  • 金额:
    $ 25.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-08-01 至 2016-07-31
  • 项目状态:
    已结题

项目摘要

The overall goals of Project 3 are to understand the high-resolution structural correlates of immunodominance and to provide structural foundations for designing immunogens that can focus an immune response on particular, chosen epitopes. Our principal hypothesis is that structural contributions to immunodominance can be revealed by correlating structures of antibody-antigen complexes with knowledge of the repertoire from which the antibody was derived and reconstruction of the mutational sequence that led to the affinity matured antibody from its germline precursor. The high-throughput approaches described in Project 1 can give us the required information about repertoire and about affinity maturation of antibodies denved from the settings of vaccination vs. infection. We propose here to provide the corresponding three-dimensional information. We have the following four Aims. [1) What are the structural characteristics of cross-reactive antibodies bound with their HA epitopes? We will determine structures of selected representatives of the antibodies studied in projects 1 and 2, in complex with the relevant influenza virus HA. We will begin with standard crystallographic approaches, but proceed as rapidly as possible to higher-throughput cryoEM methods (Aim 2; see also Core C). (2) We will develop approaches for mounting "guest proteins" [with influenza HA as the principal target) onto icosahedral-virus scaffolds, to create a symmetric array suitable for structure determination by cryoEM. We will start with the rotavirus double-layer particle (DLP) as our scaffold, and the outer-layer glycoprotein, VP7, as the mounting device.; we will also test the other outer-layer protein, VP4, as a trimeric mounting protein. [3) What makes an epitope immunodominant? The opportunity afforded by the cryoEM approach to examine a systematic and relatively unbiased set of complexes will allow us to determine the structural correlates of immunodominance directly. We will determine structures of a selected HA in complex with antibodies representing the entire spectrum of a typical repertoire as revealed by the studies in Project 1 and mapped by Project 2. [4) Application to other viral antigens. We will apply to the mounting strategies developed in Aim 2 to other viral antigens for which a combination of repertoire analysis and structural dissection might lead to novel
项目3的总体目标是了解免疫优势的高分辨率结构相关性

项目成果

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STEPHEN COPLAN HARRISON其他文献

STEPHEN COPLAN HARRISON的其他文献

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{{ truncateString('STEPHEN COPLAN HARRISON', 18)}}的其他基金

Structural biology of antibody:antigen complexes
抗体的结构生物学:抗原复合物
  • 批准号:
    8516984
  • 财政年份:
    2013
  • 资助金额:
    $ 25.75万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8516985
  • 财政年份:
    2013
  • 资助金额:
    $ 25.75万
  • 项目类别:
Structural biology of antibody:antigen complexes
抗体的结构生物学:抗原复合物
  • 批准号:
    8377204
  • 财政年份:
    2012
  • 资助金额:
    $ 25.75万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    8377206
  • 财政年份:
    2012
  • 资助金额:
    $ 25.75万
  • 项目类别:
Project #1: Harrison
项目
  • 批准号:
    8462406
  • 财政年份:
    2012
  • 资助金额:
    $ 25.75万
  • 项目类别:
Core A: Administrative Core
核心A:行政核心
  • 批准号:
    10549603
  • 财政年份:
    2011
  • 资助金额:
    $ 25.75万
  • 项目类别:
Discovery of small molecules to block fusion and entry of dengue and other env vi
发现小分子以阻止登革热和其他环境病毒的融合和进入
  • 批准号:
    8233434
  • 财政年份:
    2011
  • 资助金额:
    $ 25.75万
  • 项目类别:
Project 4: Structural Biology of Influenza Antibody-Antigen Interactions
项目4:流感抗体-抗原相互作用的结构生物学
  • 批准号:
    10549614
  • 财政年份:
    2011
  • 资助金额:
    $ 25.75万
  • 项目类别:
Structure-function analysis of infection- and vaccine-induced B-cell repertoires
感染和疫苗诱导的 B 细胞库的结构功能分析
  • 批准号:
    10549602
  • 财政年份:
    2011
  • 资助金额:
    $ 25.75万
  • 项目类别:
Structure-function analysis of infection- and vaccine-induced B-cell repertoires
感染和疫苗诱导的 B 细胞库的结构功能分析
  • 批准号:
    8303235
  • 财政年份:
    2011
  • 资助金额:
    $ 25.75万
  • 项目类别:

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