Krsmanovic V, Biquard J M, Sikorska-Walker M, Cosic I, Desgranges C, Trabaud M A, Whitfield J F, Durkin J P, Achour A, Hearn M T
Centre de Génétique Moléculaire et Cellulaire, CNRS UMR 106, Université Claude Bernard Lyon I, Villeurbanne, France.
J Pept Res. 1998 Nov;52(5):410-20. doi: 10.1111/j.1399-3011.1998.tb00665.x.
The immunological cross-reactivity of several peptides with specific pattern-property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV-1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross-react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure-function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico-chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side-chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic alpha-helices and beta-sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gp160/120 glycoproteins from a range of HIV-1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gp120. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV-1 proteins. These nonhomologous synthetic peptides induced cross-reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV-1 ENV gp120-related proteins, as determined by enzyme-linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross-reactivity and molecular biomimicry in the development of peptide-based vaccines directed against viral or bacterial pathogens.
已对几种具有与人类免疫缺陷病毒1型（HIV-1）gp160/120包膜蛋白表位相关的特定模式特性的肽的免疫交叉反应性进行了研究。具有相似一级结构的蛋白质有望表现出功能或拓扑相似性，例如可能与用同一蛋白质家族的其他成员免疫动物产生的抗体发生交叉反应的特定表位。这些结构-功能特性可能表现为基于蛋白质分子多肽主链和氨基酸侧链的各种物理化学氨基酸描述符分布的离散傅里叶变换的呈现所产生的周期性。例如，此类方法已能够预测蛋白质序列中与二级结构基序相对应的周期性，包括两亲性α螺旋和β折叠，并有助于阐明与相互作用的大分子的配体、底物或辅因子的潜在结合位点。基于此方法，已鉴定出特征性周期性，这些周期性代表了一系列HIV-1分离株包膜（ENV）gp160/120糖蛋白的常见傅里叶变换光谱特性。此外，在gp120的CD4结合域的相应氨基酸描述符的离散傅里叶变换表示中也检测到了类似的周期性。因此，我们合成了几种在其离散傅里叶变换表示中具有与这些HIV-1蛋白相似的周期性特征的肽。这些非同源合成肽在新西兰白兔中诱导了交叉反应性抗体。通过酶联免疫吸附测定和蛋白质印迹技术测定，针对其中一种肽产生的多克隆抗体与HIV-1 ENV gp120相关蛋白发生反应。这些发现为免疫交叉反应性和分子仿生学在针对病毒或细菌病原体的基于肽的疫苗开发中的作用提供了进一步的证据。
