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目的研究合成肽ＷＬＤＰＲＨ的免疫反应性和对干扰素（ＩＦＮ）诱导的生物学活性的影响。方法根据我们早先的研究，已用中和抗体从噬菌体展示６肽库中筛选出了两个与ＩＦＮ－α有同源性的肽片段，将其中之一进行了人工合成（ＷＬＤＰＲＨ），并进行了同源性比较分析，体外竞争酶联免疫吸附实验（ＥＬＩＳＡ），体外ＩＦＮ诱导抗病毒和抗增殖分析。结果计算机分析表明，人工合成肽ＷＬＤＰＲＨ与推理的Ｉ型ＩＦＮ受体结合区ＬｏｏｐＡＢ（２９－３５位）有相当的同源性。体外竞争ＥＬＩＳＡ实验表明，合成肽在２５μｇ／ｍｌ浓度时能特异性抑制ＩＦＮ－α与中和抗体４Ｃ１结合。体外抗病毒结果显示，干扰素在亚保护剂量时（２０～７０ｐｇ／ｍｌ）时，合成肽能提高ＩＦＮ－α作用细胞后的抗病毒活性，并且合成肽ＷＬＤＰＲＨ在１．４μｇ／ｍｌ时，ＩＦＮ－α抗病毒保护率从４０％提高到８６％，为最高保护率的最低剂量，但合成肽为１．４μｇ／ｍｌ，ＩＦＮ浓度为５～５５ｎｇ／ｍｌ时，对ＩＦＮ－α诱导的抗增殖作用不明显。结论用中和抗体筛选的短肽ＷＬＤＰＲＨ能影响ＩＦＮ分子作用模式，并且有可能模拟ＩＦＮ分子ＬｏｏｐＡＢ的结构和功能，这为免疫治疗及ＩＦＮ的小分子模拟设计奠定基础。
Objective To investigate the immunological reactivity of the synthetic peptide WLDPRH and its effect on interferon (IFN) -induced biological activity. Methods According to our previous study, two peptide fragments homologous to IFN-α were screened from a phage display peptide library using neutralizing antibodies and one of them was synthetically synthesized (WLDPRH) and performed Homology comparison, in vitro competitive enzyme-linked immunosorbent assay (ELISA), in vitro IFN-induced antiviral and anti-proliferative assay were also performed. Results Computer analysis showed that the synthetic peptide WLDPRH shares considerable homology with the putative type I IFN receptor binding region LoopAB (positions 29-35). In vitro competitive ELISA experiments showed that the synthetic peptide can specifically inhibit the binding of IFN-α to the neutralizing antibody 4C1 at a concentration of 25 μg / ml. In vitro antiviral results showed that the anti-viral activity of interferon at IFN-α-treated cells was significantly increased at sub-protective doses (20-70 pg / ml), and that at the concentration of 1.4 μg / ml of synthetic peptide WLDPRH, IFN Α-antiviral protection rate increased from 40% to 86%, the highest protection rate of the lowest dose, but the synthetic peptide of 1.4μg / ml, IFN concentration of 5 ~ 55ng / ml of IFN-α-induced anti-proliferation The role is not obvious. Conclusion The short peptide WLDPRH screened by neutralizing antibody can affect the mode of action of IFN molecules, and it is possible to mimic the structure and function of the IFN molecule LoopAB, which lays a foundation for the immunotherapy and the design of small molecule simulation of IFN.