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Protein-Scaffold Directed Nanoscale Assembly of T Cell Ligands: Artificial Antigen Presentation with Defined Valency, Density, and Ratio
ACS Synthetic Biology ( IF 4.7 ) Pub Date : 2018-05-07 00:00:00 , DOI: 10.1021/acssynbio.8b00119
Mason R Smith 1 , Stephanie V Tolbert 1 , Fei Wen 1
Affiliation  

Tuning antigen presentation to T cells is a critical step in investigating key aspects of T cell activation. However, existing technologies have a limited ability to control the spatial and stoichiometric organization of T cell ligands on 3D surfaces. Here, we developed an artificial antigen presentation platform based on protein scaffold-directed assembly that allows fine control over the spatial and stoichiometric organization of T cell ligands on a 3D yeast cell surface. Using this system, we observed that the T cell activation threshold on a 3D surface is independent of peptide-major histocompatibility complex (pMHC) valency but instead is determined by the overall pMHC surface density. When intercellular adhesion molecule 1 (ICAM-1) was coassembled with pMHC, it enhanced antigen recognition sensitivity by 6-fold. Further, T cells responded with different magnitudes to varying ratios of pMHC and ICAM-1 and exhibited a maximum response at a ratio of 15% pMHC and 85% ICAM-1, introducing an additional parameter for tuning T cell activation. This protein scaffold-directed assembly technology is readily transferrable to acellular surfaces for translational research as well as large-scale T-cell manufacturing.

中文翻译:

蛋白质支架定向的 T 细胞配体纳米级组装:具有确定化合价、密度和比率的人工抗原呈递

调整向 T 细胞的抗原呈递是研究 T 细胞活化的关键方面的关键步骤。然而,现有技术在控制 3D 表面上 T 细胞配体的空间和化学计量组织的能力有限。在这里,我们开发了一个基于蛋白质支架定向组装的人工抗原呈递平台,该平台允许对 3D 酵母细胞表面上 T 细胞配体的空间和化学计量组织进行精细控制。使用该系统,我们观察到 3D 表面上的 T 细胞活化阈值与肽主要组织相容性复合物 (pMHC) 的化合价无关,而是由整体 pMHC 表面密度决定。当细胞间粘附分子 1 (ICAM-1) 与 pMHC 共组装时,它将抗原识别灵敏度提高了 6 倍。进一步,T 细胞对不同比例的 pMHC 和 ICAM-1 有不同程度的反应,并在 15% pMHC 和 85% ICAM-1 的比例下表现出最大反应,为调节 T 细胞活化引入了一个额外的参数。这种蛋白质支架定向组装技术很容易转移到无细胞表面,用于转化研究和大规模 T 细胞制造。
更新日期:2018-05-07
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