富含组氨酸的对映体多肽共凝胶能增强向 T 细胞递送抗原的能力

Ushasi Pramanik, Anirban Das, Elise M. Brown, Heather L. Struckman, Huihao Wang, Samuel Stealey, Macy L. Sprunger, Wasim Abdul, Jonathan Fascetti, Jagannath Mondal, Jonathan R. Silva, Silviya P. Zustiak, Meredith E. Jackrel, Jai S. Rudra
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引用次数: 0

摘要

通过 LLPS 自组装的肽和肽模拟物因其独特的物理化学特性和动态性质,最近已成为制造功能性生物材料的构件。生命最显著的特征之一是其对手性分子的选择性,而迄今为止,由 D-氨基酸组成的共凝聚体尚未见报道。在这里,我们证明了 (GHGXY)4 (X=L/V/P)的富组氨酸重复序列及其对映体会发生 LLPS,这为提高凝聚态稳定性开辟了新的途径。通过一系列生物物理研究,我们发现 LLPS 动力学、液滴大小、融合和封装效率均由主序列决定。此外,这些共包被物还能封装治疗货物,然后通过内吞机制将其内化。最后,我们还发现这些包被物能增强 CD4+ 和 CD8+ T 细胞的抗原呈递能力,从而促进细胞增殖并产生功能性细胞因子。总之,我们的研究描述了对映体多肽共凝胶的开发和特性,它是一种具有可调理化特性的有吸引力的疫苗递送载体。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Enantiomeric histidine-rich peptide coacervates enhance antigen delivery to T cells
Peptides and peptidomimetics that self-assemble via LLPS have recently emerged as building blocks for fabricating functional biomaterials due to their unique physicochemical properties and dynamic nature. One of life's most distinctive signatures is its selectivity for chiral molecules and, to date, coacervates comprised of D-amino acids have not been reported. Here, we demonstrate that histidine-rich repeats of (GHGXY)4 (X=L/V/P) and their enantiomers undergo LLPS opening new avenues for enhancing coacervate stability. Through a series of biophysical studies, we find that LLPS kinetics, droplet size, fusion, and encapsulation efficiency are dictated by the primary sequence. Further, these coacervates can encapsulate therapeutic cargo which are then internalized via endocytic mechanisms. Finally, we show that the coacervates enhance antigen presentation to CD4+ and CD8+ T cells resulting in robust proliferation and production of functional cytokines. Collectively, our study describes the development and characterization of enantiomeric peptide coacervates as attractive vaccine delivery vehicles with tunable physicochemical properties.
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