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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhou, T; Lynch, RM; Chen, L; Acharya, P; Wu, X; Doria-Rose, NA; Joyce, MG; 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; NISC Comparative Sequencing Program, ; 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

Published Date

  • June 4, 2015

Published In

Volume / Issue

  • 161 / 6

Start / End Page

  • 1280 - 1292

PubMed ID

  • 26004070

Pubmed Central ID

  • 26004070

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.05.007

Language

  • eng

Conference Location

  • United States