A peptide-based material platform for displaying antibodies to engage T cells.
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 CD4T 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.
Zheng
Ying
Y
Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
Wen
Yi
Y
George
Amanda M
AM
Steinbach
Alison M
AM
Phillips
Brett E
BE
Giannoukakis
Nick
N
Gawalt
Ellen S
ES
Meng
Wilson S
WS
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D007074:Immunoglobulin G / Q000378:metabolism; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D007074:Immunoglobulin G; D010455:Peptides