Epitope mapping of conformational V2-specific anti-HIV human monoclonal antibodies reveals an immunodominant site in V2.
Epitope mapping of conformational V2-specific anti-HIV human monoclonal antibodies reveals an immunodominant site in V2.
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DOI：
10.1371/journal.pone.0070859
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zolla-Pazner S
中科院分区：
文献类型：
--
作者：
Mayr LM;Cohen S;Spurrier B;Kong XP;Zolla-Pazner S
在RV144疫苗试验的病例对照研究中，发现针对gp120包膜糖蛋白V1V2区域的抗体水平与艾滋病毒感染风险呈负相关。最近对V1V2作为疫苗靶标的潜在作用的这一证明使该地区成为HIV-1研究的焦点。我们之前描述了7种来自HIV感染者的针对V1V2结构域构象表位的人类单抗。在本研究中，利用携带V1V2突变的SF162假病毒裂解产物，我们绘制了这七株单抗的表位。所有测试的单抗都表现出类似的结合模式，其中三个突变(F176A、Y177T和D180L)取消了七个单抗中的至少六个与≤的结合15%的SF162野生型结合。通过7个位置(16 8、180、181、183、184、191和193)的单一替换，6个或所有单抗的结合减少到野生型的≤的50%，而一个突变V181I增加了所有单抗的结合。当映射到V2的模型上时，我们的结果表明，构象V2单抗的表位主要位于V1V2现有晶体结构的无序区域，重叠并围绕V2上的α4β7结合位点。
In the case-control study of the RV144 vaccine trial, the levels of antibodies to the V1V2 region of the gp120 envelope glycoprotein were found to correlate inversely with risk of HIV infection. This recent demonstration of the potential role of V1V2 as a vaccine target has catapulted this region into the focus of HIV-1 research. We previously described seven human monoclonal antibodies (mAbs) derived from HIV-infected individuals that are directed against conformational epitopes in the V1V2 domain. In this study, using lysates of SF162 pseudoviruses carrying V1V2 mutations, we mapped the epitopes of these seven mAbs. All tested mAbs demonstrated a similar binding pattern in which three mutations (F176A, Y177T, and D180L) abrogated binding of at least six of the seven mAbs to ≤15% of SF162 wildtype binding. Binding of six or all of the mAbs was reduced to ≤50% of wildtype by single substitutions at seven positions (168, 180, 181, 183, 184, 191, and 193), while one change, V181I, increased the binding of all mAbs. When mapped onto a model of V2, our results suggest that the epitope of the conformational V2 mAbs is located mostly in the disordered region of the available crystal structure of V1V2, overlapping and surrounding the α4β7 binding site on V2.
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影响因子：
6.7
作者：
Parrish NF;Wilen CB;Banks LB;Iyer SS;Pfaff JM;Salazar-Gonzalez JF;Salazar MG;Decker JM;Parrish EH;Berg A;Hopper J;Hora B;Kumar A;Mahlokozera T;Yuan S;Coleman C;Vermeulen M;Ding H;Ochsenbauer C;Tilton JC;Permar SR;Kappes JC;Betts MR;Busch MP;Gao F;Montefiori D;Haynes BF;Shaw GM;Hahn BH;Doms RW
通讯作者：
Doms RW
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：
5.4
作者：
GORNY, MK;MOORE, JP;ZOLLAPAZNER, S
通讯作者：
ZOLLAPAZNER, S
影响因子：
3.7
作者：
Gorny, Miroslaw K.;Pan, Ruimin;Zolla-Pazner, Susan
通讯作者：
Zolla-Pazner, Susan
影响因子：
5.4
作者：
Rong, Rong;Bibollet-Ruche, Frederic;Derdeyn, Cynthia A.
通讯作者：
Derdeyn, Cynthia A.