Structural Basis of the Cross-Reactivity of Genetically Related Human Anti-HIV-1 mAbs: Implications for Design of V3-Based Immunogens

被引：67

作者：

Burke, Valicia ^{[1
]}

Williams, Constance ^{[2
]}

Sukumaran, Madhav ^{[1
]}

Kim, Seung-Sup ^{[1
]}

Li, Huiguang ^{[1
]}

Wang, Xiao-Hong ^{[3
]}

Gorny, Miroslaw K. ^{[2
]}

Zolla-Pazner, Susan ^{[2
,3
]}

Kong, Xiang-Peng ^{[1
]}

机构：

[1] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA

[2] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[3] New York Harbor Healthcare Syst, Vet Affairs, New York, NY 10010 USA

来源：

STRUCTURE | 2009年 / 17卷 / 11期

基金：

美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; CLADE NEUTRALIZING ACTIVITY; HIV-1; GP120; ENVELOPE; V3; LOOP; IMMUNE-RESPONSE; TYPE-1; PROTEIN; EPITOPE; DOMAIN;

D O I：

10.1016/j.str.2009.09.012

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：

Human monoclonal antibodies 447-52D and 537-10D, both coded by the VH3 gene and specific for the third variable region (V3) of the HIV-1 gp120, were found to share antigen-binding structural elements including an elongated CDR H3 forming main-chain interactions with the N terminus of the V3 crown. However, water-mediated hydrogen bonds and a unique cation-pi sandwich stacking allow 447-52D to be broadly reactive with V3 containing both the GPGR and GPGQ crown motifs, while the deeper binding pocket and a buried Glu in the binding site of 537-10D limit its reactivity to only V3 containing the GPGR motif. Our results suggest that the design of immunogens for anti-V3 antibodies should avoid the Arg at the V3 crown, as GPGR-containing epitopes appear to select for B cells making antibodies of narrower specificity than V3 that carry Gln at this position.

引用

页码：1538 / 1546

页数：9

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