Fung M S, Sun C R, Liou R S, Gordon W, Chang N T, Chang T W, Sun N C
Tanox Biosystems, Inc., Houston, TX 77025.
J Immunol. 1990 Oct 1;145(7):2199-206.
A murine mAb BAT123 (Ab1) directing to the principal neutralization site of human T cell leukemia virus (HTLV)-IIIB gp120 (amino acid residue 308-322) was used to generate syngeneic anti-Id mAb (Ab2). Among the Ab2, a mAb AB19-4 was characterized by both serologic and biologic methods to be paratope-specific (Ab2 beta), bearing the internal image of the neutralization site. AB19-4 was found to bind specifically to BAT123 and also to its mouse-human chimeric form in ELISA. The binding of AB19-4 to BAT123 was specifically inhibited by HTLV-IIIB gp120 and the synthetic epitope peptides of HTLV-IIIB and HTLV-IIIMN defined by BAT123. AB19-4 also inhibited the binding of BAT123 to HTLV-IIIB-infected H9 cells in flow cytometric studies. Polyclonal goat and sheep antisera against HTLV-IIIB gp120 reacted specifically with AB19-4, suggesting that AB19-4 may recognize cross-species idiotopes. Rabbits immunized with purified AB19-4 generated anti-anti-Id antibodies (Ab3) that reacted specifically with HTLV-IIIB gp120 and the BAT123-binding epitope peptides of HTLV-IIIB and HTLV-IIIMN. The Ab3 bound to H9 cells infected by HTLV-IIIB or HTLV-IIIMN and inhibited the infection of CEM cells by HTLV-IIIB or HTLV-IIIMN, whereas BAT123 also bound H9 cells infected by HTLV-IIIB or HTLV-IIIMN but neutralized only HTLV-IIIB. Our data suggest that AB19-4 mimics the neutralization site on HIV-1 gp120 defined by BAT123. The induction of immunity to HIV using internal-image Ab2 to HIV-neutralizing antibodies may provide a viable approach for developing effective vaccines for AIDS.
一种针对人类T细胞白血病病毒（HTLV）-IIIB型gp120主要中和位点（氨基酸残基308 - 322）的鼠单克隆抗体BAT123（Ab1）被用于产生同基因抗独特型单克隆抗体（Ab2）。在这些Ab2中，单克隆抗体AB19 - 4通过血清学和生物学方法被鉴定为抗原决定部位特异性（Ab2β），具有中和位点的内影像。在酶联免疫吸附测定（ELISA）中发现AB19 - 4能特异性结合BAT123及其鼠 - 人嵌合形式。HTLV-IIIB型gp120以及由BAT123界定的HTLV-IIIB型和HTLV-IIIMN型合成表位肽可特异性抑制AB19 - 4与BAT123的结合。在流式细胞术研究中，AB19 - 4也抑制了BAT123与HTLV-IIIB感染的H9细胞的结合。针对HTLV-IIIB型gp120的多克隆山羊和绵羊抗血清与AB19 - 4发生特异性反应，表明AB19 - 4可能识别跨物种独特型表位。用纯化的AB19 - 4免疫兔子产生了抗抗独特型抗体（Ab3），其与HTLV-IIIB型gp120以及HTLV-IIIB型和HTLV-IIIMN型的BAT123结合表位肽发生特异性反应。Ab3与HTLV-IIIB或HTLV-IIIMN感染的H9细胞结合，并抑制HTLV-IIIB或HTLV-IIIMN对CEM细胞的感染，而BAT123也与HTLV-IIIB或HTLV-IIIMN感染的H9细胞结合，但仅中和HTLV-IIIB。我们的数据表明AB19 - 4模拟了由BAT123界定的HIV-1 gp120上的中和位点。利用针对HIV中和抗体的内影像Ab2诱导对HIV的免疫，可能为开发有效的艾滋病疫苗提供一种可行的方法。
