期刊
CELL
卷 153, 期 1, 页码 126-138出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.03.018
关键词
-
资金
- German Research Foundation (DFG) [KL 2389/1-1]
- Stavros Niarchos Foundation
- Robert Mapplethorpe Foundation
- German National Academic Foundation
- Vaccine Research Center, NIAID, NIH
- Bill and Melinda Gates Foundation [1032144, 38660, OPP1033115]
- CHAVI-ID Award [UM1AI100663]
- NIH grant [AI081677]
- Bill and Melinda Gates Foundation [OPP1033115] Funding Source: Bill and Melinda Gates Foundation
Broadly neutralizing antibodies (bNAbs) to HIV-1 can prevent infection and are therefore of great importance for HIV-1 vaccine design. Notably, bNAbs are highly somatically mutated and generated by a fraction of HIV-1-infected individuals several years after infection. Antibodies typically accumulate mutations in the complementarity determining region (CDR) loops, which usually contact the antigen. The CDR loops are scaffolded by canonical framework regions (FWRs) that are both resistant to and less tolerant of mutations. Here, we report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most bNAbs require somatic mutations in their FWRs. Structural and functional analyses reveal that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. Thus, in bNAbs, FWRs play an essential role beyond scaffolding the CDR loops and their unusual contribution to potency and breadth should be considered in HIV-1 vaccine design.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据