Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

被引：958

作者：

Scheid, Johannes F. ^{[1
,2
]}

Mouquet, Hugo ^{[1
]}

Ueberheide, Beatrix ^{[3
]}

Diskin, Ron ^{[4
]}

Klein, Florian ^{[1
]}

Oliveira, Thiago Y. K. ^{[1
]}

Pietzsch, John ^{[1
,5
]}

Fenyo, David ^{[3
]}

Abadir, Alexander ^{[1
]}

Velinzon, Klara ^{[1
]}

Hurley, Arlene ^{[6
]}

Myung, Sunnie ^{[3
]}

Boulad, Farid ^{[7
]}

Poignard, Pascal ^{[8
,9
,10
]}

Burton, Dennis R. ^{[8
,9
,11
]}

Pereyra, Florencia ^{[11
,12
,13
]}

Ho, David D. ^{[14
]}

Walker, Bruce D. ^{[11
,12
,13
,14
]}

Seaman, Michael S. ^{[15
]}

Bjorkman, Pamela J. ^{[4
,14
]}

Chait, Brian T. ^{[3
]}

Nussenzweig, Michel C. ^{[1
,14
]}

机构：

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

[2] Charite, D-10117 Berlin, Germany

[3] Rockefeller Univ, Lab Mass Spectrometry & Gaseous Ion Chem, New York, NY 10065 USA

[4] CALTECH, Div Biol, Pasadena, CA 91125 USA

[5] Free Univ Berlin, Dept Biol Chem & Pharm, D-14195 Berlin, Germany

[6] Rockefeller Univ, Rockefeller Univ Hosp, New York, NY 10065 USA

[7] Mem Sloan Kettering Canc Ctr, Bone Marrow Transplant Serv, New York, NY 10065 USA

[8] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[9] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

[10] Int AIDS Vaccine Initiat, New York, NY 10028 USA

[11] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

[12] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA

[13] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

[14] Howard Hughes Med Inst, New York, NY 10065 USA

[15] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA

来源：

SCIENCE | 2011年 / 333卷 / 6049期

基金：

比尔及梅琳达.盖茨基金会;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; NEUTRALIZING ANTIBODIES; TYPE-1; GP120; ENVELOPE GLYCOPROTEIN; EPITOPE; RECEPTOR; GP41; INDIVIDUALS;

D O I：

10.1126/science.1207227

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

引用

页码：1633 / 1637

页数：5

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