Matsumi S, Matsushita S, Yoshimura K, Javaherian K, Takatsuki K
Second Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
AIDS Res Hum Retroviruses. 1995 Apr;11(4):501-8. doi: 10.1089/aid.1995.11.501.
Three monoclonal antibodies (M318T, M56S and M815) against an external envelope glycoprotein (gp110) of simian immunodeficiency virus (SIV) mac251 were obtained by immunizing BALB/c mice with recombinant gp110 (rgp110). All three monoclonal antibodies reacted with the surface of cells infected with SIVmac251 but not with that of uninfected counterparts. The binding activity of these monoclonal antibodies against native gp110 was confirmed by means of Western blotting. One of them, M318T neutralized SIVmac251 infection both by cell-free and cell-associated viruses. M318T cross-reacted with human immunodeficiency virus type 2 strains (HIV-2 GH1 and ROD isolates) and SIVmac239 isolates. However, the antibody did not cross-neutralize these viral strains. Epitope mapping revealed that the neutralizing epitope recognized by M318T was localized at 8 residues between amino acids 178 and 185 (KRDKTKEY) in gp110, corresponding to the V2 region of human immunodeficiency virus type 1 (HIV-1). Because some antibodies against the V2 region of HIV-1 reportedly neutralize virus infection by interfering with CD4-gp120 interaction, we tested the activity of M318T against the binding of CD4-gp110. However, M318T did not inhibit CD4-gp110 interaction, suggesting the involvement of another unknown mechanism of M318T-mediated neutralization. In analogy with the V2 region of HIV-1, the V2 region of SIV contains a type specific neutralizing epitope recognized by M318T. Although some amino acid sequence in the epitope was conserved for the isolates of SIV and HIV-2 and there was cross-reactivity of the antibody against the strains, neutralization by M318T was associated with a single amino acid (182 T) in the epitope.
通过用重组猿猴免疫缺陷病毒（SIV）mac251包膜糖蛋白（gp110）（rgp110）免疫BALB/c小鼠，获得了三种针对SIV mac251外膜糖蛋白（gp110）的单克隆抗体（M318T、M56S和M815）。所有这三种单克隆抗体均与感染SIVmac251的细胞表面发生反应，但不与未感染细胞的表面发生反应。通过蛋白质印迹法证实了这些单克隆抗体对天然gp110的结合活性。其中之一，M318T可通过游离病毒和细胞相关病毒中和SIVmac251感染。M318T与人免疫缺陷病毒2型毒株（HIV-2 GH1和ROD分离株）及SIVmac239分离株发生交叉反应。然而，该抗体并未交叉中和这些病毒株。表位作图显示，M318T识别的中和表位位于gp110中氨基酸178至185之间的8个残基（KRDKTKEY）处，对应于人类免疫缺陷病毒1型（HIV-1）的V2区。因为据报道一些针对HIV-1 V2区的抗体通过干扰CD4-gp120相互作用来中和病毒感染，所以我们测试了M318T对CD4-gp110结合的活性。然而，M318T并未抑制CD4-gp110相互作用，这表明M318T介导的中和作用涉及另一种未知机制。与HIV-1的V2区类似，SIV的V2区含有一个被M318T识别的型特异性中和表位。尽管该表位中的一些氨基酸序列在SIV和HIV-2分离株中是保守的，并且该抗体与这些毒株存在交叉反应，但M318T的中和作用与表位中的单个氨基酸（182 T）有关。
