Revisiting the CD14: epitope mapping by Phage Display

Immunobiology. 2014 Nov;219(11):822-9. doi: 10.1016/j.imbio.2014.07.002. Epub 2014 Aug 10.

Abstract

The cluster of differentiation antigen 14 (CD14) is a key molecule of the innate immunity. This pattern recognition receptor binds mainly to lipopolysaccharide (LPS), lipotechoic acid (LTA), arachidonic acid, and thus induces the releases various cytokines, as a defense mechanism. Several studies suggest that different regions of the amino-terminal portion of the molecule may be involved in the LPS binding; however, controversial results on the recognition sequence still persist. In this work, functional epitopes of the CD14 molecule were mapped through Phage Display by using a 7-mer conformational constrained random peptide library against a monoclonal antibody anti-soluble CD14-fraction ST and a polyclonal anti-CD14. In silico and empirical analyses were performed to map the selected peptides into the CD14 3D structure. Immunoreactivity tests of peptides against bacterial components of Gram+ and Gram- bacteria were performed in order to demonstrate their functional recognition. All peptides strongly reacted against all bacteria, and besides the recognition of the amino-terminal region, we were able to demonstrate a second epitope site in the middle of the receptor. Additional in silico analysis suggests a possible role of CD14 epitopes as natural antimicrobial peptides.

Keywords: CD14; Epitope mapping; LPS receptor; Phage Display.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacteria / immunology
  • Cell Surface Display Techniques*
  • Computational Biology
  • Epitope Mapping* / methods
  • Humans
  • Immunity, Innate
  • Lipopolysaccharide Receptors / chemistry
  • Lipopolysaccharide Receptors / immunology*
  • Lipopolysaccharides / immunology
  • Models, Molecular
  • Molecular Mimicry
  • Molecular Sequence Data
  • Peptide Library*
  • Peptides / chemistry
  • Peptides / immunology
  • Protein Conformation

Substances

  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Peptide Library
  • Peptides