Tongqing Zhou, Rebecca M Lynch, Lei Chen, Priyamvada Acharya, Xueling Wu, Nicole A Doria-Rose, M Gordon Joyce, Daniel Lingwood, Cinque Soto, Robert T Bailer, Michael J Ernandes, Rui Kong, Nancy S Longo, Mark K Louder, Krisha McKee, Sijy O'Dell, Stephen D Schmidt, Lillian Tran, Zhongjia Yang, Aliaksandr Druz, Timothy S Luongo, Stephanie Moquin, Sanjay Srivatsan, Yongping Yang, Baoshan Zhang, Anqi Zheng, Marie Pancera, Tatsiana Kirys, Ivelin S Georgiev, Tatyana Gindin, Hung-Pin Peng, An-Suei Yang, James C Mullikin, Matthew D Gray, Leonidas Stamatatos, Dennis R Burton, Wayne C Koff, Myron S Cohen, Barton F Haynes, Joseph P Casazza, Mark Connors, Davide Corti, Antonio Lanzavecchia, Quentin J Sattentau, Robin A Weiss, Anthony P West, Pamela J Bjorkman, Johannes F Scheid, Michel C Nussenzweig, Lawrence Shapiro, John R Mascola, Peter D Kwong
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...
June 4, 2015: Cell