Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.

TitleStructural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.
Publication TypeJournal Article
Year of Publication2015
AuthorsZhou T, Lynch RM, Chen L, Acharya P, Wu X, Doria-Rose NA, M Joyce G, Lingwood D, Soto C, Bailer RT, Ernandes MJ, Kong R, Longo NS, Louder MK, McKee K, O'Dell S, Schmidt SD, Tran L, Yang Z, Druz A, Luongo TS, Moquin S, Srivatsan S, Yang Y, Zhang B, Zheng A, Pancera M, Kirys T, Georgiev IS, Gindin T, Peng H-P, Yang A-S, Mullikin JC, Gray MD, Stamatatos L, Burton DR, Koff WC, Cohen MS, Haynes BF, Casazza JP, Connors M, Corti D, Lanzavecchia A, Sattentau QJ, Weiss RA, West AP, Bjorkman PJ, Scheid JF, Nussenzweig MC, Shapiro L, Mascola JR, Kwong PD
Corporate AuthorsNISC Comparative Sequencing Program
JournalCell
Volume161
Issue6
Pagination1280-92
Date Published06/04/2015
ISSN1097-4172
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.

DOI10.1016/j.cell.2015.05.007
Alternate JournalCell
PubMed ID26004070
Grant List1UM1 AI100663 / AI / NIAID NIH HHS / United States
AI037526 / AI / NIAID NIH HHS / United States
AI0678501 / AI / NIAID NIH HHS / United States
AI072529 / AI / NIAID NIH HHS / United States
P01 AI094419 / AI / NIAID NIH HHS / United States
P01 AI094419 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
P01 AI100148 / AI / NIAID NIH HHS / United States
P01AI104722 / AI / NIAID NIH HHS / United States
UM1 AI100645 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
CHAVI-ID: 
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