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通过两种单克隆抗体的独特型模拟鉴定人类免疫缺陷病毒1型糖蛋白gp120/gp41相互作用位点

Identification of human immunodeficiency virus type 1 glycoprotein gp120/gp41 interacting sites by the idiotypic mimicry of two monoclonal antibodies.

作者信息

Lopalco L, Longhi R, Ciccomascolo F, De Rossi A, Pelagi M, Andronico F, Moore J P, Schulz T, Beretta A, Siccardi A G

机构信息

Centro San Luigi H.S.R. Milano, Italy.

出版信息

AIDS Res Hum Retroviruses. 1993 Jan;9(1):33-9. doi: 10.1089/aid.1993.9.33.

DOI:10.1089/aid.1993.9.33
PMID:7678970
Abstract

A sequence of four amino acid residues amino-terminal to the only intramolecular disulphide bond of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein gp41 is recognized by an anti-idiotypic antibody (9G5A) raised against another monoclonal antibody (M38), which recognizes the C5 region of gp120. 9G5A is an Ab2 beta antibody (internal image of the M38 epitope) in that it inhibits the interaction of M38 to its antigen. The binding of 9G5A to gp41 can be inhibited by M38 showing that the two antibodies interact via their paratopes. 9G5A neutralizes HIV-1 infection and syncytia formation. Ab3 antibodies induced in mice and rabbits immunized with 9G5A also can neutralize virus in both assays. These data show that the M38-defined epitope of the carboxy-terminal region of gp120 interacts with the 9G5A-defined epitope of gp41, and that this interaction can be reproduced by the idiotypic mimicry of the two antibodies. The results are consistent with a proposed molecular model of the two env regions which predicts the presence, within the C5 region of gp120, of a large intramolecular pocket that is contacted by the gp41 cysteine loop.

摘要

人免疫缺陷病毒1型(HIV-1)跨膜蛋白gp41唯一分子内二硫键氨基端的四个氨基酸残基序列,可被一种抗独特型抗体(9G5A)识别,该抗体是针对另一种识别gp120 C5区的单克隆抗体(M38)产生的。9G5A是一种Ab2β抗体(M38表位的内影像),因为它能抑制M38与其抗原的相互作用。M38可抑制9G5A与gp41的结合,表明这两种抗体通过其互补位相互作用。9G5A可中和HIV-1感染及合胞体形成。用9G5A免疫的小鼠和兔诱导产生的Ab3抗体在两种检测中也能中和病毒。这些数据表明,gp120羧基端区域的M38定义表位与gp41的9G5A定义表位相互作用,且这种相互作用可通过两种抗体的独特型模拟来重现。结果与两个env区域的分子模型一致,该模型预测在gp120的C5区域内存在一个大的分子内口袋,gp41半胱氨酸环可与之接触。

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