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

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

doi:10.1016/j.cell.2015.05.007

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

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 DruzTimothy 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

Research output: Contribution to journal › Article › peer-review

263 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1280-1292
Number of pages	13
Journal	Cell
Volume	161
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2015.05.007
Publication status	Published - Jun 5 2015
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cell.2015.05.007

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Zhou, T., Lynch, R. M., Chen, L., Acharya, P., Wu, X., Doria-Rose, N. A., Joyce, M. G., Lingwood, D., Soto, C., Bailer, R. T., Ernandes, M. J., Kong, R., Longo, N. S., Louder, M. K., McKee, K., O'Dell, S., Schmidt, S. D., Tran, L., Yang, Z., ... Shapiro, L. (2015). Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell, 161(6), 1280-1292. https://doi.org/10.1016/j.cell.2015.05.007

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, HP, Yang, AS, 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 2015, 'Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors', Cell, vol. 161, no. 6, pp. 1280-1292. https://doi.org/10.1016/j.cell.2015.05.007

@article{d20c564b44484455a12358cf7c8adff7,

title = "Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

month = jun,

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doi = "10.1016/j.cell.2015.05.007",

language = "English",

volume = "161",

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T1 - Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors

AU - Zhou, Tongqing

AU - Lynch, Rebecca M.

AU - Chen, Lei

AU - Acharya, Priyamvada

AU - Wu, Xueling

AU - Doria-Rose, Nicole A.

AU - Joyce, M. Gordon

AU - Lingwood, Daniel

AU - Soto, Cinque

AU - Bailer, Robert T.

AU - Ernandes, Michael J.

AU - Kong, Rui

AU - Longo, Nancy S.

AU - Louder, Mark K.

AU - McKee, Krisha

AU - O'Dell, Sijy

AU - Schmidt, Stephen D.

AU - Tran, Lillian

AU - Yang, Zhongjia

AU - Druz, Aliaksandr

AU - Luongo, Timothy S.

AU - Moquin, Stephanie

AU - Srivatsan, Sanjay

AU - Yang, Yongping

AU - Zhang, Baoshan

AU - Zheng, Anqi

AU - Pancera, Marie

AU - Kirys, Tatsiana

AU - Georgiev, Ivelin S.

AU - Gindin, Tatyana

AU - Peng, Hung Pin

AU - Yang, An Suei

AU - Mullikin, James C.

AU - Gray, Matthew D.

AU - Stamatatos, Leonidas

AU - Burton, Dennis R.

AU - Koff, Wayne C.

AU - Cohen, Myron S.

AU - Haynes, Barton F.

AU - Casazza, Joseph P.

AU - Connors, Mark

AU - Corti, Davide

AU - Lanzavecchia, Antonio

AU - Sattentau, Quentin J.

AU - Weiss, Robin A.

AU - West, Anthony P.

AU - Bjorkman, Pamela J.

AU - Scheid, Johannes F.

AU - Nussenzweig, Michel C.

AU - Shapiro, Lawrence

PY - 2015/6/5

Y1 - 2015/6/5

N2 - 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.

AB - 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.

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DO - 10.1016/j.cell.2015.05.007

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AN - SCOPUS:84930418589

SN - 0092-8674

VL - 161

SP - 1280

EP - 1292

JO - Cell

JF - Cell

IS - 6

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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