Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
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DOI：
10.1038/nature07930
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发表时间：
2009-04-02
期刊：
影响因子：
64.8
通讯作者：
Nussenzweig, Michel C.
中科院分区：
文献类型：
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作者：
Scheid, Johannes F.;Mouquet, Hugo;Nussenzweig, Michel C.
人类免疫缺陷病毒（HIV）表面蛋白gp140上保守表位的抗体可以保护非人灵长类动物免受感染，并且一些感染个体在其血清中显示高滴度的广泛中和免疫球蛋白（Ig）G抗体。然而，对这些抗体的特异性和活性知之甚少（1-3）。为了表征记忆抗体对HIV的反应，我们从6名具有广泛中和抗体和低到中等病毒载量的HIV感染患者的HIV包膜结合记忆B细胞中克隆了502种抗体。我们发现，在这些患者中，b细胞对gp140的记忆反应由多达50个独立的克隆组成，这些克隆对gp120可变环、cd4结合位点、共受体结合位点以及gp120与cd4结合位点相同区域的一个新的中和表位表达高亲和力的中和抗体。因此，在对HIV具有广泛血清中和活性的选定患者组中，IgG记忆b细胞区室由针对gp120上几个表位具有中和活性的多个克隆应答组成。
Antibodies to conserved epitopes on the human immunodeficiency virus (HIV) surface protein gp140 can protect against infection in non-human primates, and some infected individuals show high titres of broadly neutralizing immunoglobulin (Ig)G antibodies in their serum. However, little is known about the specificity and activity of these antibodies(1-3). To characterize the memory antibody responses to HIV, we cloned 502 antibodies from HIV envelope-binding memory B cells from six HIV-infected patients with broadly neutralizing antibodies and low to intermediate viral loads. We show that in these patients, the B-cell memory response to gp140 is composed of up to 50 independent clones expressing high affinity neutralizing antibodies to the gp120 variable loops, the CD4-binding site, the co-receptor-binding site, and to a new neutralizing epitope that is in the same region of gp120 as the CD4-binding site. Thus, the IgG memory B-cell compartment in the selected group of patients with broad serum neutralizing activity to HIV is comprised of multiple clonal responses with neutralizing activity directed against several epitopes on gp120.