Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120

被引：197

作者：

West, Anthony P., Jr. ^{[1
]}

Diskin, Ron ^{[1
]}

Nussenzweig, Michel C. ^{[3
,4
]}

Bjorkman, Pamela J. ^{[1
,2
]}

机构：

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

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

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

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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 30期

基金：

美国国家卫生研究院;

关键词：

analysis; selection; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; RATIONAL DESIGN; BROAD; VACCINE; BINDING; EPITOPE; INDIVIDUALS;

D O I：

10.1073/pnas.1208984109

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：

A large number of anti-HIV-1 antibodies targeting the CD4-binding site (CD4bs) on the envelope glycoprotein gp120 have recently been reported. These antibodies, typified by VRC01, are remarkable for both their breadth and their potency. Crystal structures have revealed a common mode of binding for several of these antibodies; however, the precise relationship among CD4bs antibodies remains to be defined. Here we analyze existing structural and sequence data, propose a set of signature features for potent VRC01-like (PVL) antibodies, and verify the importance of these features by mutagenesis. The signature features explain why PVL antibodies derive from a single germ-line human V-H gene segment and why certain gp120 sequences are associated with antibody resistance. Our results bear on vaccine development and structure-based design to improve the potency and breadth of anti-CD4bs antibodies.

引用

页码：E2083 / E2090

页数：8

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