A peptide-based material platform for displaying antibodies to engage T cells

详细信息    查看全文

• 作者：Ying Zheng ; Yi Wen ; Am ; a M. George ; Alison M. Steinbach ; Brett E. Phillips ; Nick Giannoukakis ; Ellen S. Gawalt ; Wilson S. Meng
• 关键词：Amphiphilic peptides ; Self-assembly material ; T cells ; Clustered antibodies
• 刊名：Biomaterials
• 出版年：2011
• 出版时间：January 2011
• 年：2011
• 卷：32
• 期：1
• 页码：249-257
• 全文大小：1516 K

文摘

This study investigated a strategy by which antibodies are displayed to engage T cells. A peptide composite containing binding sites was characterized in vitro and explored as an injectable system in vivo. The composite consists of two amphiphilic peptides, AEAEAKAKAEAEAKAK (referred to as “EAK”) and EAK appended with six consecutive histidines at the C-terminus (“EAKH6”). Spectroscopic analysis showed the two peptides integrated into a single structure. Prior to combination, conformational analysis revealed that EAKH6 adopts a mixed α-helix/β-strand conformation. In the presence of EAK, EAKH6 exists predominately in β-strand conformation. The composite of EAK-EAKH6 was found to display His-tags, using nickel-bound horseradish peroxidase as a probe. T cell-specific antibodies were found stably displayed on the EAK-EAKH6 assembly using recombinant protein A/G and anti-histidines antibody as an adaptor. When mounted with anti-CD4 antibody, the system was shown to capture CD4 T cells in a mixed population of lymphocytes. Antibodies were concentrated in the subcutaneous space in mice when co-administered with EAK and EAKH6 along with protein A/G and anti-histidines antibody as a solution.

We report here the use of amphiphilic peptides to display Ab in vivo, the results indicating that the design can be used as a platform for engaging specific subsets of leukocytes for the purpose of immune modulation.