Department of Respiratory Medicine, Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Hannover Medical School, 30625 Hannover, Germany.
Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, Germany.
Int J Mol Sci. 2021 Feb 21;22(4):2141. doi: 10.3390/ijms22042141.
The C-terminal-fragments of alpha1-antitrypsin (AAT) have been identified and their diverse biological roles have been reported in vitro and in vivo. These findings prompted us to develop a monoclonal antibody that specifically recognizes C-36 peptide (corresponding to residues 359-394) resulting from the protease-associated cleavage of AAT. The C-36-targeting mouse monoclonal Immunoglobulin M (IgM) antibody (containing κ light chains, clone C42) was generated and enzyme-linked immunosorbent assay (ELISA)-tested by Davids Biotechnologie GmbH, Germany. Here, we addressed the effectiveness of the novel C42 antibody in different immunoassay formats, such as dot- and Western blotting, confocal laser microscopy, and flow cytometry. According to the dot-blot results, our novel C42 antibody detects the C-36 peptide at a range of 0.1-0.05 µg and shows no cross-reactivity with native, polymerized, or oxidized forms of full-length AAT, the AAT-elastase complex mixture, as well as with shorter C-terminal fragments of AAT. However, the C42 antibody does not detect denatured peptide in SDS-PAGE/Western blotting assays. On the other hand, our C42 antibody, unconjugated as well as conjugated to DyLight488 fluorophore, when applied for immunofluorescence microscopy and flow cytometry assays, specifically detected the C-36 peptide in human blood cells. Altogether, we demonstrate that our novel C42 antibody successfully recognizes the C-36 peptide of AAT in a number of immunoassays and has potential to become an important tool in AAT-related studies.
α1-抗胰蛋白酶 (AAT) 的 C 端片段已被鉴定,其在体外和体内的多种生物学作用也已有报道。这些发现促使我们开发一种特异性识别 AAT 蛋白酶相关切割产生的 C-36 肽(对应于残基 359-394)的单克隆抗体。德国 Davids Biotechnologie GmbH 生成了靶向 C-36 的小鼠单克隆免疫球蛋白 M (IgM) 抗体(含 κ 轻链,克隆 C42),并通过酶联免疫吸附试验 (ELISA) 进行了测试。在这里,我们评估了新型 C42 抗体在不同免疫分析方法中的有效性,如斑点和 Western 印迹、共聚焦激光显微镜和流式细胞术。根据斑点印迹结果,我们的新型 C42 抗体可在 0.1-0.05μg 范围内检测到 C-36 肽,且与天然、聚合或氧化形式的全长 AAT、AAT-弹性蛋白酶复合物混合物以及 AAT 的较短 C 端片段均无交叉反应。然而,C42 抗体在 SDS-PAGE/Western 印迹分析中无法检测到变性肽。另一方面,我们的 C42 抗体,无论是未缀合还是与 DyLight488 荧光团缀合,当应用于免疫荧光显微镜和流式细胞术分析时,均可特异性地检测到人血细胞中的 C-36 肽。总之,我们证明了我们的新型 C42 抗体可成功识别多种免疫分析中的 AAT 的 C-36 肽,并有潜力成为 AAT 相关研究中的重要工具。