MIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Manipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodies

Author(s)
Wang, Shenshen; Mata-Fink, Jordi; Kriegsman, Barry; Irvine, Darrell J.; Eisen, Herman N.; Burton, Dennis R.; Kardar, Mehran; Chakraborty, Arup K.; Wittrup, Karl Dane; Eisen, Herman N.; Hanson, Melissa Catherine; Irvine, Darrell J; Chakraborty, Arup K; ... Show more Show less
Thumbnail
DownloadManipulating the Selection.pdf (1.623Mb)
PUBLISHER_CC

Publisher with Creative Commons License

Creative Commons Attribution

Terms of use
Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/
Metadata
Show full item record
Abstract
Generation of potent antibodies by a mutation-selection process called affinity maturation is a key component of effective immune responses. Antibodies that protect against highly mutable pathogens must neutralize diverse strains. Developing effective immunization strategies to drive their evolution requires understanding how affinity maturation happens in an environment where variants of the same antigen are present. We present an in silico model of affinity maturation driven by antigen variants which reveals that induction of cross-reactive antibodies often occurs with low probability because conflicting selection forces, imposed by different antigen variants, can frustrate affinity maturation. We describe how variables such as temporal pattern of antigen administration influence the outcome of this frustrated evolutionary process. Our calculations predict, and experiments in mice with variant gp120 constructs of the HIV envelope protein confirm, that sequential immunization with antigen variants is preferred over a cocktail for induction of cross-reactive antibodies focused on the shared CD4 binding site epitope.
Date issued
2015-02
URI
http://hdl.handle.net/1721.1/101768
Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Physics; Ragon Institute of MGH, MIT and Harvard; Koch Institute for Integrative Cancer Research at MIT
Journal
Cell
Publisher
Elsevier
Citation
Wang, Shenshen, Jordi Mata-Fink, Barry Kriegsman, Melissa Hanson, Darrell J. Irvine, Herman N. Eisen, Dennis R. Burton, K. Dane Wittrup, Mehran Kardar, and Arup K. Chakraborty. “Manipulating the Selection Forces During Affinity Maturation to Generate Cross-Reactive HIV Antibodies.” Cell 160, no. 4 (February 2015): 785–797.
Version: Author's final manuscript
ISSN
00928674
1097-4172

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries
PrivacyPermissionsAccessibilityContact us
MIT
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.