Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.
Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.
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DOI：
10.1126/sciimmunol.aal2200
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发表时间：
2017-01-27
影响因子：
24.8
通讯作者：
Haynes BF
中科院分区：
文献类型：
--
作者：
Williams LD;Ofek G;Schätzle S;McDaniel JR;Lu X;Nicely NI;Wu L;Lougheed CS;Bradley T;Louder MK;McKee K;Bailer RT;O'Dell S;Georgiev IS;Seaman MS;Parks RJ;Marshall DJ;Anasti K;Yang G;Nie X;Tumba NL;Wiehe K;Wagh K;Korber B;Kepler TB;Munir Alam S;Morris L;Kamanga G;Cohen MS;Bonsignori M;Xia SM;Montefiori DC;Kelsoe G;Gao F;Mascola JR;Moody MA;Saunders KO;Liao HX;Tomaras GD;Georgiou G;Haynes BF
诱导广谱中和抗体(BNAbs)是HIV-1疫苗开发的目标之一。抗体10E8与HIV-1gp41的膜近端外区(MPER)的远端部分发生反应，具有广泛的中和作用。然而，远端MPER抗体的个体发育以及记忆B细胞与血浆bNAbs的关系尚不清楚。应用HIV-1特异性记忆B细胞流分选和抗MPER血浆抗体的蛋白质组学鉴定，分离同一B细胞克隆系的远端广泛中和MPER bNAb。结构分析表明，来自记忆B细胞和血浆的抗体识别包膜gp41bNab表位的方向与其他MPER远端bNAb不同。这个远端MPER bNab的未突变的共同祖先是自身反应的，提示谱系免疫耐受控制。构建记忆B细胞和血浆抗体的嵌合抗体产生了一种能有效中和大多数HIV-1毒株的bNab。
Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of distal MPER antibodies and the relationship of memory B cell to plasma bnAbs are poorly understood. HIV-1–specific memory B cell flow sorting and proteomic identification of anti-MPER plasma antibodies from an HIV-1–infected individual were used to isolate broadly neutralizing distal MPER bnAbs of the same B cell clonal lineage. Structural analysis demonstrated that antibodies from memory B cells and plasma recognized the envelope gp41 bnAb epitope in a distinct orientation compared with other distal MPER bnAbs. The unmutated common ancestor of this distal MPER bnAb was autoreactive, suggesting lineage immune tolerance control. Construction of chimeric antibodies of memory B cell and plasma antibodies yielded a bnAb that potently neutralized most HIV-1 strains.
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影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Gray, Elin S.;Madiga, Maphuti C.;Morris, Lynn
通讯作者：
Morris, Lynn
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH
影响因子：
15.8
作者：
Gray ES;Meyers T;Gray G;Montefiori DC;Morris L
通讯作者：
Morris L