Developing cell-specific antibodies to endothelial progenitor cells using avian immune phage display technology

J Biomol Screen. 2011 Aug;16(7):744-54. doi: 10.1177/1087057111407067. Epub 2011 May 18.

Abstract

This study aims at generating immune chicken phage display libraries and single-chain antibodies (scFvs) specifically directed against cell surface markers of cultured peripheral blood mononuclear cells (PBMCs) that contain endothelial progenitor cells (EPCs). In contrast to previous approaches that use well-defined recombinant antigens attached to plastic surfaces that may alter the structure of the proteins, the authors describe a method that maintains the cell surface markers on live cells while providing the opportunity to rapidly screen entire libraries for antibodies that bind to unknown cell surface markers of progenitor/stem cells. Chickens immunized with live EPCs, consisting of a heterogeneous population of lymphocytes and monocytes, demonstrated a robust immune response. After three rounds of biopanning, the authors purified and characterized three unique scFvs called UG1-3. Codon-optimized recombinant UG1 (gUG-1) shows binding by flow cytometry to circulating CD14-positive cells in peripheral blood consistent with predominant expression of a target protein on monocyte subsets. The authors describe the successful use of immunization of chickens for the generation of scFvs against a heterogenous population of EPCs displaying unknown cell surface markers and demonstrate the strong potential of phage display technology in the development of reagents for the isolation and characterization of stem/progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • Chickens / immunology
  • Endothelial Cells / immunology*
  • Endothelial Cells / metabolism
  • Epitopes / immunology
  • Flow Cytometry
  • Humans
  • Immunization
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Molecular Sequence Data
  • Peptide Library*
  • Protein Binding / immunology
  • Sequence Alignment
  • Single-Chain Antibodies / immunology*
  • Single-Chain Antibodies / isolation & purification
  • Stem Cells / immunology*
  • Stem Cells / metabolism

Substances

  • Antigens, Surface
  • Epitopes
  • Peptide Library
  • Single-Chain Antibodies