Targeting membrane proteins for antibody discovery using phage display

Sci Rep. 2016 May 18:6:26240. doi: 10.1038/srep26240.

Abstract

A critical factor in the successful isolation of new antibodies by phage display is the presentation of a correctly folded antigen. While this is relatively simple for soluble proteins which can be purified and immobilized onto a plastic surface, membrane proteins offer significant challenges for antibody discovery. Whole cell panning allows presentation of the membrane protein in its native conformation, but is complicated by a low target antigen density, high background of irrelevant antigens and non-specific binding of phage particles to cell surfaces. The method described here uses transient transfection of alternating host cell lines and stringent washing steps to address each of these limitations. The successful isolation of antibodies from a naive scFv library is described for three membrane bound proteins; human CD83, canine CD117 and bat CD11b.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibody Specificity
  • Antigens, CD / immunology
  • CD11b Antigen / immunology
  • CD83 Antigen
  • CHO Cells
  • Cell Surface Display Techniques / methods*
  • Chiroptera
  • Cricetulus
  • Dogs
  • HEK293 Cells
  • Humans
  • Immunoglobulins / immunology
  • Membrane Glycoproteins / immunology
  • Membrane Proteins / immunology*
  • Peptide Library
  • Proto-Oncogene Proteins c-kit / immunology
  • Transfection

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • CD11b Antigen
  • Immunoglobulins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Peptide Library
  • Proto-Oncogene Proteins c-kit