The Wistar Institute, Philadelphia, PA.
Jonathan Lax Immune Disorders Treatment Center, Philadelphia Field Initiating Group for HIV-1 Trials, Philadelphia, PA.
J Immunol. 2024 Sep 15;213(6):808-822. doi: 10.4049/jimmunol.2400265.
Type I IFNs play a pivotal role in immune response modulation, yet dysregulation is implicated in various disorders. Therefore, it is crucial to develop tools that facilitate the understanding of their mechanism of action and enable the development of more effective anti-IFN therapeutic strategies. In this study, we isolated, cloned, and characterized anti-IFN-α and anti-IFN-β Abs from PBMCs of individuals treated with IFN-α or IFN-β, harboring confirmed neutralizing Abs. Clones AH07856 and AH07857 were identified as neutralizing anti-IFN-α-specific with inhibition against IFN-α2a, -α2b, and -αK subtypes. Clones AH07859 and AH07866 were identified as neutralizing anti-IFN-β1a-specific signaling and able to block lipopolysaccharide or S100 calcium-binding protein A14-induced IFN-β signaling effects. Cloned Abs bind rhesus but not murine IFNs. The specificity of inhibition between IFN-α and IFN-β suggests potential for diverse research and clinical applications.
I 型干扰素在免疫反应调节中发挥关键作用，但失调与各种疾病有关。因此，开发有助于理解其作用机制并能够开发更有效的抗 IFN 治疗策略的工具至关重要。在这项研究中，我们从接受 IFN-α或 IFN-β治疗的个体的 PBMC 中分离、克隆和鉴定了抗 IFN-α和抗 IFN-β Abs，这些 Abs 具有已确认的中和 Abs。克隆 AH07856 和 AH07857 被鉴定为针对 IFN-α2a、-α2b 和-αK 亚型的中和抗 IFN-α特异性。克隆 AH07859 和 AH07866 被鉴定为中和抗 IFN-β1a 特异性信号，并能够阻断脂多糖或 S100 钙结合蛋白 A14 诱导的 IFN-β信号效应。克隆 Abs 结合恒河猴而不是鼠 IFN。IFN-α 和 IFN-β 之间抑制的特异性表明具有多种研究和临床应用的潜力。
