Human anti-V3 HIV-1 monoclonal antibodies encoded by the VH5-51/VL lambda genes define a conserved antigenic structure.
Human anti-V3 HIV-1 monoclonal antibodies encoded by the VH5-51/VL lambda genes define a conserved antigenic structure.
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DOI：
10.1371/journal.pone.0027780
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kong XP
中科院分区：
文献类型：
--
作者：
Gorny MK;Sampson J;Li H;Jiang X;Totrov M;Wang XH;Williams C;O'Neal T;Volsky B;Li L;Cardozo T;Nyambi P;Zolla-Pazner S;Kong XP
免疫球蛋白（IG）基因编码的抗体（抗体）对各种病原体的优先使用是很少观察到的，其优势的性质是不清楚的背景下，随机重组的IG基因。在本研究中，对IG基因的限制性使用预先决定抗体特异性的假设进行了测试，该研究使用了18种人抗V3单克隆抗体（mAb），这些抗体均由感染各种HIV-1亚型的无关个体产生，所有这些抗体均优先使用VH 5 -51和VL λ基因的配对。与各种V3肽复合的五个VH 5 -51/VL cDNA编码的Fab的晶体学分析揭示了抗原结合位点的共同三维（3D）形状，其主要由重（H）和轻（L）链的四个互补决定区（CDR）确定：具体地，H1、H2、L1和L2结构域。CDR H3结构域对结合口袋的形状没有贡献，因为它对于每种mAb具有不同的长度、序列和构象。通过与Fab复合的V3肽所表现出的相同骨架构象进一步证实了结合位点的相同形状，所述Fab完全适应结合口袋和相同的关键接触残基，主要是在5个Fab的重链和轻链中种系编码的。最后，VH 5 -51抗V3 mAb识别具有相同3D结构的表位，该表位被大多数VH 5 -51衍生的mAb识别的单一模拟表位模拟，但不被其他V3 mAb识别。这些数据表明，优先使用的IG基因的中和单克隆抗体的鉴定可能会定义在不同的病毒包膜保守的表位。这将为设计疫苗免疫原诱导交叉中和抗体提供有用的信息。
Preferential usage of immunoglobulin (Ig) genes that encode antibodies (Abs) against various pathogens is rarely observed and the nature of their dominance is unclear in the context of stochastic recombination of Ig genes. The hypothesis that restricted usage of Ig genes predetermines the antibody specificity was tested in this study of 18 human anti-V3 monoclonal Abs (mAbs) generated from unrelated individuals infected with various subtypes of HIV-1, all of which preferentially used pairing of the VH5-51 and VL lambda genes. Crystallographic analysis of five VH5-51/VL lambda-encoded Fabs complexed with various V3 peptides revealed a common three dimensional (3D) shape of the antigen-binding sites primarily determined by the four complementarity determining regions (CDR) for the heavy (H) and light (L) chains: specifically, the H1, H2, L1 and L2 domains. The CDR H3 domain did not contribute to the shape of the binding pocket, as it had different lengths, sequences and conformations for each mAb. The same shape of the binding site was further confirmed by the identical backbone conformation exhibited by V3 peptides in complex with Fabs which fully adapted to the binding pocket and the same key contact residues, mainly germline-encoded in the heavy and light chains of five Fabs. Finally, the VH5-51 anti-V3 mAbs recognized an epitope with an identical 3D structure which is mimicked by a single mimotope recognized by the majority of VH5-51-derived mAbs but not by other V3 mAbs. These data suggest that the identification of preferentially used Ig genes by neutralizing mAbs may define conserved epitopes in the diverse virus envelopes. This will be useful information for designing vaccine immunogen inducing cross-neutralizing Abs.
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影响因子：
6.4
作者：
Andrus, L;Prince, AM;Zolla-Pazner, S
通讯作者：
Zolla-Pazner, S
影响因子：
3.7
作者：
Corti D;Langedijk JP;Hinz A;Seaman MS;Vanzetta F;Fernandez-Rodriguez BM;Silacci C;Pinna D;Jarrossay D;Balla-Jhagjhoorsingh S;Willems B;Zekveld MJ;Dreja H;O'Sullivan E;Pade C;Orkin C;Jeffs SA;Montefiori DC;Davis D;Weissenhorn W;McKnight A;Heeney JL;Sallusto F;Sattentau QJ;Weiss RA;Lanzavecchia A
通讯作者：
Lanzavecchia A
影响因子：
5.6
作者：
CHOTHIA, C;LESK, AM
通讯作者：
LESK, AM
影响因子：
5.4
作者：
Gorny, MK;Revesz, K;Zolla-Pazner, S
通讯作者：
Zolla-Pazner, S
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL