Prevention of cell death by antibodies selected from intracellular combinatorial libraries.
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.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jia
J
Xie
Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 200031, China.
Kyungmoo
K
Yea
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hongkai
H
Zhang
Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brian
B
Moldt
Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Linling
L
He
Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jiang
J
Zhu
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: rlerner@scripps.edu.
Richard A
RA
Lerner
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D019151:Peptide Library; D010641:Phenotype; D012229:Rhinovirus / Q000201:enzymology / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism
D000906:Antibodies; D022801:Complementarity Determining Regions; D019151:Peptide Library; D014764:Viral Proteins; D010447:Peptide Hydrolases