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

被引：266

作者：

Zhou, Tongqing ^{[1
,2
]}

Lynch, Rebecca M. ^{[1
,2
]}

Chen, Lei ^{[1
,2
]}

Acharya, Priyamvada ^{[1
,2
]}

Wu, Xueling ^{[1
,2
]}

Doria-Rose, Nicole A. ^{[1
,2
]}

Joyce, M. Gordon ^{[1
,2
]}

Lingwood, Daniel ^{[1
,2
]}

Soto, Cinque ^{[1
,2
]}

Bailer, Robert T. ^{[1
,2
]}

Ernandes, Michael J. ^{[1
,2
]}

Kong, Rui ^{[1
,2
]}

Longo, Nancy S. ^{[1
,2
]}

Louder, Mark K. ^{[1
,2
]}

McKee, Krisha ^{[1
,2
]}

O'Dell, Sijy ^{[1
,2
]}

Schmidt, Stephen D. ^{[1
,2
]}

Tran, Lillian ^{[1
,2
]}

Yang, Zhongjia ^{[1
,2
]}

Druz, Aliaksandr ^{[1
,2
]}

Luongo, Timothy S. ^{[1
,2
]}

Moquin, Stephanie ^{[1
,2
]}

Srivatsan, Sanjay ^{[1
,2
]}

Yang, Yongping ^{[1
,2
]}

Zhang, Baoshan ^{[1
,2
]}

Zheng, Anqi ^{[1
,2
]}

Pancera, Marie ^{[1
,2
]}

Kirys, Tatsiana ^{[1
,2
]}

Georgiev, Ivelin S. ^{[1
,2
]}

Gindin, Tatyana ^{[3
,4
]}

Peng, Hung-Pin ^{[5
,6
]}

Yang, An-Suei ^{[5
,6
]}

Mullikin, James C. ^{[7
]}

Gray, Matthew D. ^{[8
]}

Stamatatos, Leonidas ^{[8
]}

Burton, Dennis R. ^{[9
,10
]}

Koff, Wayne C. ^{[11
]}

Cohen, Myron S. ^{[12
,13
,14
,15
]}

Haynes, Barton F. ^{[16
,17
,18
,19
,20
]}

Casazza, Joseph P. ^{[1
,2
]}

Connors, Mark ^{[21
,22
]}

Corti, Davide ^{[23
,24
]}

Lanzavecchia, Antonio ^{[24
]}

Sattentau, Quentin J. ^{[25
]}

Weiss, Robin A. ^{[26
]}

West, Anthony P., Jr. ^{[27
]}

Bjorkman, Pamela J. ^{[27
,28
]}

Scheid, Johannes F. ^{[29
]}

Nussenzweig, Michel C. ^{[29
,30
]}

Shapiro, Lawrence ^{[1
,2
,3
,4
]}

机构：

[1] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA

[2] NIH, Bethesda, MD 20892 USA

[3] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA

[4] Columbia Univ, Dept Syst Biol, New York, NY 10032 USA

[5] Acad Sinica, Genom Res Ctr, Taipei 11221, Taiwan

[6] Natl Yang Ming Univ, Inst Biomed Informat, Taipei 11221, Taiwan

[7] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA

[8] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

[9] Scripps Res Inst, Dept Immunol & Microbial Sci, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[10] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02142 USA

[11] Int AIDS Vaccine Initiat, New York, NY 10038 USA

[12] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA

[13] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA

[14] Univ N Carolina, Dept Microbiol, Chapel Hill, NC 27599 USA

[15] Univ N Carolina, Dept Immunol, Chapel Hill, NC 27599 USA

[16] Duke Univ, Sch Med, Human Vaccine Inst, Dept Med, Durham, NC 27710 USA

[17] Duke Univ, Sch Med, Human Vaccine Inst, Dept Surg, Durham, NC 27710 USA

[18] Duke Univ, Sch Med, Human Vaccine Inst, Dept Pediat, Durham, NC 27710 USA

[19] Duke Univ, Sch Med, Human Vaccine Inst, Dept Immunol, Durham, NC 27710 USA

[20] Duke Univ, Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC 27710 USA

[21] NIAID, HIV Specif Immun Sect, Immunoregulat Lab, Bethesda, MD 20892 USA

[22] NIH, Bethesda, MD 20892 USA

[23] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland

[24] Univ Svizzera Italiana, Inst Res Biomed, CH-6500 Bellinzona, Switzerland

[25] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RF, England

[26] UCL, Div Infect Immun, London WC1E 6BT, England

[27] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[28] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

[29] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[30] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA

来源：

CELL | 2015年 / 161卷 / 06期

基金：

美国国家卫生研究院;

关键词：

NEUTRALIZING HIV-1 ANTIBODY; CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODIES; POTENT NEUTRALIZATION; CD4-BINDING SITE; BROAD; COMPLEX; DETERMINANTS; RECOGNITION; MATURATION;

D O I：

10.1016/j.cell.2015.05.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 V-H-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 V-H-gene-restricted ontogenies.

引用

页码：1280 / 1292

页数：13

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