Single chain antibodies specific for fatty acids derived from a semi-synthetic phage display library

Biochim Biophys Acta. 2002 Jan 15;1569(1-3):167-73. doi: 10.1016/s0304-4165(01)00245-8.

Abstract

The biological activities of many acylated molecules are lipid dependent. Lipids, however, are poorly immunogenic or non-immunogenic. We employed a phage display semi-synthetic human antibody library to isolate anti-lipid antibodies. Selection was done against methyl palmitate, a 16 carbon aliphatic chain, and a major component of bacterial glycolipids and lipoproteins in animal cells. The selected single chain variable fragment (scFv) bound specifically to a 16 carbon aliphatic chain and to a lesser extent to a 14 or 18 carbon aliphatic chain and poorly to either 12, 22 or 8 carbon aliphatic chains. Furthermore, the scFv prevented micelle formation of lipoteichoic acid from Gram-positive bacteria; inhibited lipopolysaccharide-induced tumor necrosis factor alpha release in mononuclear cells; bound to hydrophobic bacterial surfaces, especially those of Gram-positive bacteria, and bound to Lck, a mammalian palmitated lipoprotein. Our data suggest that the phage antibody library can be successfully employed to obtain human anti-aliphatic scFv human antibody fragment with potential therapeutic applications in neutralizing the deleterious effects of bacterial toxins as well as in structure--function analysis of lipoproteins in animal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / immunology*
  • Bacteriophage M13 / genetics*
  • Bacteriophage M13 / immunology
  • Fatty Acids / immunology*
  • Glycolipids / immunology
  • Gram-Positive Bacteria / immunology
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin Variable Region / immunology
  • Palmitates / immunology
  • Peptide Library

Substances

  • Antibodies
  • Fatty Acids
  • Glycolipids
  • Immunoglobulin Variable Region
  • Palmitates
  • Peptide Library
  • methyl palmitate