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Controlled Lengthwise Assembly of Helical Peptide Nanofibers to Modulate CD8+ T?Cell Responses

Rationally designed peptides control the assembly of ??helical peptide nanofibers, allowing the adjustment of nanofiber length within the range of >1 µm to 100 nm. Shortened nanofibers, while raising equivalent B?cell responses compared to full?length fibers, induce heightened CD8+ T?cell responses in mice.Peptide nanofibers are useful for many biological applications, including immunotherapy, tissue engineering, and drug delivery. The robust lengthwise assembly of these peptides into nanofibers is typically difficult to control, resulting in polydisperse fiber lengths and an incomplete understanding of how nanofiber length affects biological responses. Here, rationally designed capping peptides control the length of helical peptide nanofibers with unique precision. These designed peptides bind the tips of elongated nanofibers to shorten and narrow their length distributions. Demonstrating their use as immunotherapies, capped nanofibers are preferentially cross?presented by dendritic cells compared to uncapped nanofibers. Due to increased cross?presentation, these capped nanofibers trigger stronger CD8+ T?cell responses in mice than uncapped nanofibers. This strategy illustrates a means for controlling the length of supramolecular peptide nanofibers to modulate their immunogenicity in the context of immunotherapies.

Publication date: 20/08/2020

Author: Chelsea N. Fries, Yaoying Wu, Sean H. Kelly, Michelle Wolf, Nicole L. Votaw, Stefan Zauscher, Joel H. Collier

Reference: doi:10.1002/adma.202003310

Advanced Materials


This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870292.