Mittelman Abraham, Lucchese Alberta, Sinha Animesh A, Kanduc Darja
Department of Medicine, Division of Oncology/Hematology, New York Medical College, Valhalla NY, USA.
Int J Cancer. 2002 Apr 10;98(5):741-7. doi: 10.1002/ijc.10259.
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.
我们正在研究肽免疫原性与宿主蛋白质组相似性水平之间的关系。以乳腺癌/前列腺癌相关的HER-2/neu抗原作为模型，我们分析了针对宿主蛋白质组中不存在的HER-2/neu肽基序的单克隆和多克隆体液免疫反应。我们在此表明：（i）一种针对人HER-2/neu癌蛋白细胞外结构域（EC）产生的小鼠单克隆抗体（MAb）识别出一种与小鼠蛋白质组具有低相似性水平的线性肽基序；（ii）同样，来自乳腺癌/前列腺癌患者的人血清优先识别HER-2/neu癌蛋白EC中那些在人蛋白质组中不存在序列的肽片段。结合之前在其他疾病模型（宫颈癌相关的HPV16 E7癌蛋白和寻常型天疱疮自身抗原桥粒芯糖蛋白-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塑造B细胞表位库的一个重要因素。
