Monoclonal and polyclonal humoral immune response to EC HER-2/neu peptides with low similarity to the host's proteome

Monoclonal and polyclonal humoral immune response to EC HER-2/neu peptides with low similarity to the host's proteome
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DOI:
10.1002/ijc.10259
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发表时间:
2002-04-10
影响因子:
6.4
通讯作者:
Kanduc, D
Kanduc, D
中科院分区:
医学1区
文献类型:
--
作者:
Mittelman, A;Lucchese, A;Kanduc, D

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我们正在研究肽免疫原性与宿主蛋白质组相似程度的关系。通过使用乳腺癌/前列腺癌相关HER-2/neu抗原作为模型,我们分析了针对与宿主蛋白质组不共享的HER-2/neu肽基序的单克隆和多克隆体液免疫应答。我们在这里证明(i)针对人HER-2/neu癌蛋白细胞外结构域(EC)的小鼠单克隆抗体(MAb)识别了与小鼠蛋白质组具有低相似性的线性肽基序;(ii)同样,来自乳腺癌/前列腺癌患者的人类血清优先识别HER-2/neu癌蛋白EC的肽片段,其序列在人类蛋白质组中不存在。结合先前在其他疾病模型(宫颈癌相关HPV16 E7癌蛋白和寻常型天疱疮自身抗原粘粒蛋白-3)中获得的结果,目前的数据表明,与宿主蛋白质组的低水平序列相似性可能是形成B细胞表位池的重要因素。(C) 2002 Wiley-Liss, Inc。
We are studying peptide immunogenicity as a function of the similarity level to the host's proteome. By using as a model the breast/prostate cancer-associated HER-2/neu antigen, we analyzed the monoclonal and polyclonal humoral immune responses against HER-2/neu peptide motifs not shared with the host proteome. We show here that (i) a mouse monoclonal antibody (MAb) raised against the extracellular domain (EC) of human HER-2/neu oncoprotein recognized a linear peptide motif endowed with low similarity level to the mouse proteome; (ii) likewise, human sera from breast/prostate cancer patients preferentially recognized peptide fragments from the EC of the HER-2/neu oncoprotein having sequences that are not present in the human proteome. Together with previous results obtained in other disease models (cervical cancer-associated HPV16 E7 oncoprotein and Pemphigus vulgaris auto-antigen desmoglein-3) the present data suggest that a low level of sequence similarity to the host's proteome might be an important factor in shaping the pool of B cell epitopes. (C) 2002 Wiley-Liss, Inc.