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Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies.


ABSTRACT: Eliciting antibodies that are cross reactive with surface proteins of diverse strains of highly mutable pathogens (e.g., HIV, influenza) could be key for developing effective universal vaccines. Mutations in the framework regions of such broadly neutralizing antibodies (bnAbs) have been reported to play a role in determining their properties. We used molecular dynamics simulations and models of affinity maturation to study specific bnAbs against HIV. Our results suggest that there are different classes of evolutionary lineages for the bnAbs. If germline B cells that initiate affinity maturation have high affinity for the conserved residues of the targeted epitope, framework mutations increase antibody rigidity as affinity maturation progresses to evolve bnAbs. If the germline B cells exhib

SUBMITTER: Ovchinnikov V 

PROVIDER: S-EPMC5828663 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature