Prevention of cell death by antibodies selected from intracellular combinatorial libraries.

TitlePrevention of cell death by antibodies selected from intracellular combinatorial libraries.
Publication TypeJournal Article
Year of Publication2014
AuthorsXie J, Yea K, Zhang H, Moldt B, He L, Zhu J, Lerner RA
JournalChem Biol
Volume21
Issue2
Pagination274-83
Date Published02/20/2014
ISSN1879-1301
KeywordsAmino Acid Sequence, Antibodies, Apoptosis, Complementarity Determining Regions, HeLa Cells, Humans, Molecular Sequence Data, Peptide Hydrolases, Peptide Library, Phenotype, Rhinovirus, Viral Proteins
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.

DOI10.1016/j.chembiol.2013.12.006
Alternate JournalChem. Biol.
PubMed ID24440080
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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