Department of Surgery, University of Chicago, 5841 S. Maryland Ave, Chicago, IL 60637, USA.
Biomaterials. 2010 Nov;31(32):8475-83. doi: 10.1016/j.biomaterials.2010.07.068. Epub 2010 Aug 12.
Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, and immune responses against them were investigated in mice. Experimental groups spanned a range of oligomerization behaviors and included a peptide from the coiled coil region of mouse fibrin that did not form supramolecular structures, an engineered version of this peptide that formed coiled coil bundles, and a peptide-PEG-peptide triblock bioconjugate that formed coiled coil multimers and supramolecular aggregates. In mice, the native peptide and engineered peptide did not produce any detectable antibody response, and none of the materials elicited detectable peptide-specific T cell responses, as evidenced by the absence of IL-2 and interferon-gamma in cultures of peptide-challenged splenocytes or draining lymph node cells. However, specific antibody responses were elevated in mice injected with the multimerizing peptide-PEG-peptide. Minimal changes in secondary structure were observed between the engineered peptide and the triblock peptide-PEG-peptide, making it possible that the triblock's multimerization was responsible for this antibody response.
近年来，自组装技术被越来越多地用于创建基于肽的生物材料，用于三维细胞培养、组织工程和再生医学，但这些材料免疫原性的分子决定因素在很大程度上仍未得到探索。在这项研究中，设计并合成了一组通过卷曲螺旋寡聚化自组装的分子，并在小鼠中研究了它们的免疫反应。实验组涵盖了一系列的寡聚化行为，包括来自小鼠纤维蛋白卷曲螺旋区的肽，该肽不形成超分子结构，该肽的工程化版本形成卷曲螺旋束，以及形成卷曲螺旋多聚体和超分子聚集体的肽-PEG-肽三嵌段生物缀合物。在小鼠中，天然肽和工程肽没有产生任何可检测到的抗体反应，而且这些材料都没有引起可检测到的肽特异性 T 细胞反应，这从肽挑战脾细胞或引流淋巴结细胞培养物中缺乏 IL-2 和干扰素-γ中可以看出。然而，注射多聚化肽-PEG-肽的小鼠中特异性抗体反应升高。在工程肽和三嵌段肽-PEG-肽之间观察到二级结构的微小变化，这使得三嵌段的多聚化可能是这种抗体反应的原因。
