| Literature DB >> 26004070 |
Tongqing Zhou1, Rebecca M Lynch1, Lei Chen1, Priyamvada Acharya1, Xueling Wu1, Nicole A Doria-Rose1, M Gordon Joyce1, Daniel Lingwood1, Cinque Soto1, Robert T Bailer1, Michael J Ernandes1, Rui Kong1, Nancy S Longo1, Mark K Louder1, Krisha McKee1, Sijy O'Dell1, Stephen D Schmidt1, Lillian Tran1, Zhongjia Yang1, Aliaksandr Druz1, Timothy S Luongo1, Stephanie Moquin1, Sanjay Srivatsan1, Yongping Yang1, Baoshan Zhang1, Anqi Zheng1, Marie Pancera1, Tatsiana Kirys1, Ivelin S Georgiev1, Tatyana Gindin2, Hung-Pin Peng3, An-Suei Yang3, James C Mullikin4, Matthew D Gray5, Leonidas Stamatatos5, Dennis R Burton6, Wayne C Koff7, Myron S Cohen8, Barton F Haynes9, Joseph P Casazza1, Mark Connors10, Davide Corti11, Antonio Lanzavecchia12, Quentin J Sattentau13, Robin A Weiss14, Anthony P West15, Pamela J Bjorkman16, Johannes F Scheid17, Michel C Nussenzweig18, Lawrence Shapiro19, John R Mascola20, Peter D Kwong21.
Abstract
The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.Entities:
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Year: 2015 PMID： 26004070 PMCID： PMC4683157 DOI： 10.1016/j.cell.2015.05.007
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582