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针对一种合成肽的抗体特性,该合成肽代表了 I 型细胞因子家族受体的共同表位。

Properties of antibodies to a synthetic peptide representing an epitope shared by receptors of the type I cytokine family.

机构信息

Facultad de Farmacia y Bioquímica, Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Buenos Aires, Argentina.

出版信息

Clin Exp Med. 2013 Feb;13(1):49-57. doi: 10.1007/s10238-012-0177-6.

Abstract

Previous works from our laboratory demonstrated that the monoclonal antibody (MAb) called R7B4 is directed to an epitope shared by various receptors corresponding to the type I cytokine receptor family, containing the common motif WSXWS or the homologous F(Y)GEFS. Later a consensus peptide significantly recognized by the MAb was identified and synthesized (sequence HGYWSEWSPE). In the present work, an homologous of the consensus sequence (HHGYWSEWSPE) was conjugated to PADRE adjuvant to produce Ab that could simulate theMAb activity, that is, acting as hormone and/or cytokine antagonists. The covalently conjugated peptide-PADRE was a better immunogen than the consensus peptide alone according to the reactivity of sera from C57BL/6 immunized mice and, besides, no Ab to PADRE were detected. Furthermore, Ab to consensus peptide elicited after peptide-PADRE inoculation into mice behaved as immunomodulatory agents, since they improved the humoral response to a foreign antigen (in this case ovalbumin). In addition, the Ab inhibited the in vitro proliferation of various cell lines, mainly cells derived from human and mouse breast cancer. Thus, immunization with the conjugate peptide-PADRE prepared under the experimental conditions described herein originated immunomodulatory Ab that, in the future, could be tested in some pathological conditions.

摘要

先前,我们实验室的研究工作表明,一种被称为 R7B4 的单克隆抗体(MAb)针对的是一个表位,该表位存在于各种受体中,这些受体对应于 I 型细胞因子受体家族,包含常见的 WSXWS 基序或同源的 F(Y)GEFS。后来,我们鉴定并合成了一种能被 MAb 显著识别的共有肽(序列为 HGYWSEWSPE)。在本研究中,将共有序列的同源物(HHGYWSEWSPE)与 PADRE 佐剂缀合,产生可模拟 MAb 活性的 Ab,即充当激素和/或细胞因子拮抗剂。与单独的共有肽相比,共价连接的肽-PADRE 作为免疫原的效果更好,这可以根据免疫 C57BL/6 小鼠的血清反应性来判断,此外,没有检测到针对 PADRE 的 Ab。此外,在向小鼠接种肽-PADRE 后产生的针对共有肽的 Ab 表现出免疫调节作用,因为它们提高了对异源抗原(在这种情况下为卵清蛋白)的体液反应。此外,Ab 抑制了各种细胞系的体外增殖,主要是源自人乳腺癌和小鼠乳腺癌的细胞。因此,用在本文所述实验条件下制备的缀合肽-PADRE 进行免疫接种会产生免疫调节 Ab,这些 Ab 将来可以在某些病理条件下进行测试。

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