Unknown

Dataset Information

0

Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.


ABSTRACT: Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of influenza HA. We show by analysis of structures, binding kinetics and long time-scale molecular dynamics simulations that antibody evolution in this lineage has rigidified the initially flexible heavy-chain complementarity determining region by two nearly independent pathways and that this preconfiguration accounts for most of the affinity gain. The results advance our understanding of strategies for developing more broadly effective influenza vaccines.

SUBMITTER: Schmidt AG 

PROVIDER: S-EPMC3538208 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

Preconfiguration of the antigen-binding site during affinity maturation of a broadly neutralizing influenza virus antibody.

Schmidt Aaron G AG   Xu Huafeng H   Khan Amir R AR   O'Donnell Timothy T   Khurana Surender S   King Lisa R LR   Manischewitz Jody J   Golding Hana H   Suphaphiphat Pirada P   Carfi Andrea A   Settembre Ethan C EC   Dormitzer Philip R PR   Kepler Thomas B TB   Zhang Ruijun R   Moody M Anthony MA   Haynes Barton F BF   Liao Hua-Xin HX   Shaw David E DE   Harrison Stephen C SC  

Proceedings of the National Academy of Sciences of the United States of America 20121121 1


Affinity maturation refines a naive B-cell response by selecting mutations in antibody variable domains that enhance antigen binding. We describe a B-cell lineage expressing broadly neutralizing influenza virus antibodies derived from a subject immunized with the 2007 trivalent vaccine. The lineage comprises three mature antibodies, the unmutated common ancestor, and a common intermediate. Their heavy-chain complementarity determining region inserts into the conserved receptor-binding pocket of  ...[more]

Similar Datasets

| S-EPMC4368477 | biostudies-literature
2019-08-13 | GSE135761 | GEO
| S-EPMC3161572 | biostudies-literature
| S-EPMC4924800 | biostudies-literature
| S-EPMC5115987 | biostudies-literature
| S-EPMC8476123 | biostudies-literature
| S-EPMC6801110 | biostudies-literature
| S-EPMC5535819 | biostudies-literature
| S-EPMC8317614 | biostudies-literature
| S-EPMC9020693 | biostudies-literature