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 preconfig

SUBMITTER: Schmidt AG 

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

REPOSITORIES: biostudies-literature