Prevention of cell death by antibodies selected from intracellular combinatorial libraries

Chem Biol. 2014 Feb 20;21(2):274-83. doi: 10.1016/j.chembiol.2013.12.006. Epub 2014 Jan 16.

Abstract

One of the most important phenotypes in biology is cell death. One way to probe the mechanism(s) of cell death is to select molecules that prevent it and learn how this was accomplished. Here, intracellular combinatorial antibody libraries were used to select antibodies that protected cells from killing by rhinovirus infection. These rare antibodies functioned by inhibiting the virus-encoded protease that is necessary for viral maturation. Snapshots of the selection process after each round could be obtained by deep sequencing the ever-enriching populations. This detailed analysis of the enrichment process allowed an interesting look at a "test tube" selection process that pitted two replicating systems against each other. Thus, initially a minority of cells containing protective antibodies must compete against a majority of unprotected cells that continue to produce large amounts of virus.

MeSH terms

  • Amino Acid Sequence
  • Antibodies / immunology*
  • Apoptosis
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / metabolism
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Peptide Hydrolases / metabolism
  • Peptide Library*
  • Phenotype
  • Rhinovirus / enzymology
  • Rhinovirus / metabolism
  • Viral Proteins / metabolism

Substances

  • Antibodies
  • Complementarity Determining Regions
  • Peptide Library
  • Viral Proteins
  • Peptide Hydrolases