Role of framework mutations and antibody flexibility in the evolution of broadly neutralizing antibodies
Name
elife-33038-v2.pdf
Size
2.19 MB
Format
Adobe PDF
Checksum (MD5)
555769326fa079d795164d77863c2715
Author(s)
Karplus, Martin
Ovchinnikov, Victor A
Louveau, Joy E
Barton, John P
Chakraborty, Arup K
Date Issued
February 2018
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Ovchinnikov, Victor et al. “Role of Framework Mutations and Antibody Flexibility in the Evolution of Broadly Neutralizing Antibodies.” eLife 7 (February 2018): e33038 © Ovchinnikov et al
Version
Final published version
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 exhibit weak/moderate affinity for conserved residues, an initial increase in flexibility via framework mutations may be required for the evolution of bnAbs. Subsequent mutations that increase rigidity result in highly potent bnAbs. Implications of our results for immunogen design are discussed.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/eLife.33038
