Kontsek P, Borecký L, Kontseková E, Novák M, Krchnák V
Institute of Virology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
J Interferon Res. 1990 Apr;10(2):119-28. doi: 10.1089/jir.1990.10.119.
An until now unobserved consistent antigenic structure, tentatively named "common epitope 1," was detected on molecules of human recombinant (rHu) IFN-alpha 2 and natural HuIFN-beta by testing with monoclonal and polyclonal antibodies. The monoclonal antibody B6, obtained after immunization of BALB/c mice with human fibroblast IFN-beta, was capable of binding and neutralizing both IFN-alpha 2 and natural IFN-beta. The neutralizing activity of monoclonal antibody B6 was completely inhibited by a synthetic hexapeptide which corresponded to the amino acid sequence of IFN-alpha 2 in positions 132-137. Although a corresponding sequence of amino acids in the IFN-beta molecule was localized to the region 134-139 and shows only a 66% homology with the assumed IFN-alpha 2 binding site, lysine at position 132 in IFN-alpha 2 and at position 134 in IFN-beta seems to be crucial for establishment of the common epitope. Its existence was supported by experiments using polyclonal antibodies. Antiserum to IFN-alpha 2 showed cross-neutralization with IFN-beta, and vice versa, antiserum to IFN-beta cross-reacted with IFN-alpha 2. The ability for cross-neutralization by both polyclonal antisera was abolished in the presence of IFN-alpha 2 hexapeptide SH 132-137. No cross-reacting epitope could be detected on the IFN-alpha 1 molecule. These findings are the first evidence of a homology between human IFNs of alpha and beta types at the antigenic level. They indicate that the antigenic distinction between IFNs of alpha and beta types is not absolute.
通过使用单克隆抗体和多克隆抗体进行检测,在人重组(rHu)IFN-α2和天然HuIFN-β分子上检测到一种迄今为止未被观察到的一致抗原结构,暂命名为“共同表位1”。用人类成纤维细胞IFN-β免疫BALB/c小鼠后获得的单克隆抗体B6,能够结合并中和IFN-α2和天然IFN-β。单克隆抗体B6的中和活性被一种合成六肽完全抑制,该六肽对应于IFN-α2第132 - 137位的氨基酸序列。尽管IFN-β分子中相应的氨基酸序列定位于134 - 139区域,与假定的IFN-α2结合位点仅显示66%的同源性,但IFN-α2中第132位的赖氨酸和IFN-β中第134位的赖氨酸似乎对共同表位的形成至关重要。使用多克隆抗体进行的实验支持了其存在。IFN-α2的抗血清与IFN-β表现出交叉中和作用,反之亦然,IFN-β的抗血清与IFN-α2发生交叉反应。在存在IFN-α2六肽SH 132 - 137的情况下,两种多克隆抗血清的交叉中和能力均被消除。在IFN-α1分子上未检测到交叉反应表位。这些发现是α型和β型人干扰素在抗原水平上存在同源性的首个证据。它们表明α型和β型干扰素之间的抗原区别并非绝对。