The interactions of peptides with the innate immune system studied with use of T7 phage peptide display
| Autor: | Ildiko Bock, Guofeng Zhang, Magdolna G. Sebestyén, Alex V. Sokoloff, Jon A. Wolff |
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| Rok vydání: | 2000 |
| Předmět: |
Phage display
T7 phage Phagemid Genetic Vectors Biology Ligands Chromatography Affinity Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Antibody Specificity Peptide Library Bacteriophage T7 Drug Discovery Genetics Escherichia coli Animals Humans Peptide library Molecular Biology Complement Activation 030304 developmental biology Pharmacology 0303 health sciences Innate immune system biology.organism_classification Molecular biology Blood proteins Complement system Immunoglobulin A Rats C-Reactive Protein Immunoglobulin M Immunoglobulin G Antibody Formation biology.protein Molecular Medicine Tyrosine Female Antibody Peptides 030215 immunology |
| Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy. 2(2) |
| ISSN: | 1525-0016 |
| Popis: | The icosahedral T7 phage (diameter approximately 65 nm) displaying random peptides at the carboxy-terminus of the phage coat proteins was used as a model for drug and gene delivery vehicles containing peptide ligands. We found that displayed peptides were recognized by natural antibodies and induced complement activation. Strikingly, the phage inactivation by complement was peptide-specific that implied the existence of numerous natural antibodies with different peptide specificity. Selection of phage that avoided inactivation by complement allowed the identification of peptides that protected the phage by binding to serum proteins. In rat blood, peptides with carboxy-terminal lysine or arginine residues protected the phage against complement-mediated inactivation by binding C-reactive protein. In human serum, a number of protective peptides with tyrosine residues were selected. The recognition of displayed peptides by natural antibodies appears to represent a universal mechanism for activation of complement at sites that contain identical or homologous proteins with exposed carboxy-termini. |
| Databáze: | OpenAIRE |
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