Bharathkar Sonya Kumar, Miller Michael J, Stadtmueller Beth M
Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, Illinois 61801 USA.
Carle R. Woese Institute of Genomic Biology.
bioRxiv. 2023 Nov 12:2023.11.08.566291. doi: 10.1101/2023.11.08.566291.
Secretory (S) Immunoglobin (Ig) A is the predominant mucosal antibody, which mediates host interactions with commensal and pathogenic microbes, including . SIgA adopts a polymeric IgA structure that is bound by secretory component (SC). Despite significance, how SIgA supports diverse effector mechanisms is poorly characterized and SIgA-based therapies nonexistent. We engineered chimeric (c) SIgAs, in which we replaced SC domain D2 with a single domain antibody or a monomeric fluorescent protein, allowing us to investigate and enhance SIgA effector mechanisms. cSIgAs exhibited increased neutralization potency against toxins, promoted bacterial clumping and cell rupture, and decreased cytotoxicity. cSIgA also allowed us to visualize and/or quantify morphological changes and clumping events. Results reveal mechanisms by which SIgA combats infection, demonstrate that cSIgA design can modulate these mechanisms, and demonstrate cSIgA's adaptability to modifications that might target a broad range of antigens and effector mechanisms.
分泌型（S）免疫球蛋白（Ig）A是主要的黏膜抗体，它介导宿主与共生微生物和致病微生物的相互作用，包括……分泌型IgA采用由分泌成分（SC）结合的聚合IgA结构。尽管具有重要意义，但分泌型IgA如何支持多种效应机制的特征尚不明确，基于分泌型IgA的疗法也不存在。我们设计了嵌合（c）分泌型IgA，其中我们用单域抗体或单体荧光蛋白取代了SC结构域D2，这使我们能够研究和增强分泌型IgA的效应机制。嵌合分泌型IgA对……毒素表现出更高的中和效力，促进细菌聚集和细胞破裂，并降低细胞毒性。嵌合分泌型IgA还使我们能够可视化和/或量化……形态变化和聚集事件。结果揭示了分泌型IgA对抗……感染的机制，证明嵌合分泌型IgA的设计可以调节这些机制，并证明嵌合分泌型IgA对可能针对广泛抗原和效应机制的修饰具有适应性。
