Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors

Item Type:	Article
Title:	Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors
Creators Name:	Zhou, T. and Lynch, R.M. and Chen, L. and Acharya, P. and Wu, X. and Doria-Rose, N.A. and Joyce, M.G. and Lingwood, D. and Soto, C. and Bailer, R.T. and Ernandes, M.J. and Kong, R. and Longo, N.S. and Louder, M.K. and McKee, K. and O'Dell, S. and Schmidt, S.D. and Tran, L. and Yang, Z. and Druz, A. and Luongo, T.S. and Moquin, S. and Srivatsan, S. and Yang, Y. and Zhang, B. and Zheng, A. and Pancera, M. and Kirys, T. and Georgiev, I.S. and Gindin, T. and Peng, H.P. and Yang, A.S. and Mullikin, J.C. and Gray, M.D. and Stamatatos, L. and Burton, D.R. and Koff, W.C. and Cohen, M.S. and Haynes, B.F. and Casazza, J.P. and Connors, M. and Corti, D. and Lanzavecchia, A. and Sattentau, Q.J. and Weiss, R.A. and West, A.P. and Bjorkman, P.J. and Scheid, J.F. and Nussenzweig, M.C. and Shapiro, L. and Mascola, J.R. and Kwong, P.D.
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.
Keywords:	Amino Acid Sequence, B-Lymphocytes, B-Lymphocyte Epitopes, CD4 Antigens, Complementarity Determining Regions, HIV Envelope Protein gp120, HIV-1, Molecular Models, Molecular Sequence Data, Neutralizing Antibodies, Sequence Alignment, Viral Antibodies
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	161
Number:	6
Page Range:	1280-92
Date:	4 June 2015
Additional Information:	Copyright © 2015 Elsevier Inc. All rights reserved.
Official Publication:	https://doi.org/10.1016/j.cell.2015.05.007
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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