Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.
Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.
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抗独特型单克隆抗体在猴子体内引发广泛中和抗 gp120 抗体。
DOI：
10.1073/pnas.89.7.2546
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发表时间：
1992
影响因子：
11.1
通讯作者：
Köhler,H
中科院分区：
文献类型：
--
作者：
Kang,CY;Nara,P;Chamat,S;Caralli,V;Chen,A;Nguyen,ML;Yoshiyama,H;Morrow,WJ;Ho,DD;Köhler,H
鼠单克隆抗体（mAb）针对人、多克隆、抗gp 120抗体（Ab 1）产生，并被选择用于结合人免疫缺陷病毒（HIV）阳性血清中的广泛中和抗gp 120抗体。发现一种抗独特型mAb（Ab 2）3C 9对针对gp 120的保守CD 4附着位点周围的表位的人抗gp 120抗体具有特异性。3C 9反应性人抗gp 120抗体（3C 9 + Ab）中和MN、IIIB、RF和4种HIV 1型（HIV-1）原代分离株。用佐剂中的3C 9免疫食蟹猴，以测试该抗独特型mAb是否可以诱导中和性抗gp 120抗体。结果显示，来自3C 9免疫血清的纯化的抗-抗-独特型抗体（Ab 3）结合至gp 120 SF和gp 120 IIIB的CD 4附着位点周围的表位。此外，纯化的gp 120特异性Ab 3中和MN、IIIB和RF分离物。这些结果表明，用抗独特型mAb免疫的灵长类动物产生广泛中和的抗HIV-1抗体。由于该抗独特型mAb是通过鉴定克隆型标记物选择的，因此其生物学活性可以解释为克隆型B细胞刺激的结果。
Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.