Skip to main content Accessibility help
×
Home

Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates

  • Richard A. Lerner (a1) (a2), Rajesh K. Grover (a1), Hongkai Zhang (a1), Jia Xie (a1), Kyung Ho Han (a1), Yingjie Peng (a1) and Kyungmoo Yea (a3)...

Abstract

To date, most antibodies from combinatorial libraries have been selected purely on the basis of binding. However, new methods now allow selection on the basis of function in animal cells. These selected agonist antibodies have given new insights into the important problem of signal transduction. Remarkably, when some antibodies bind to a given receptor they induce a cell fate that is different than that induced by the natural agonist to the same receptor. The fact that receptors can be functionally pleiotropic may yield new insights into the important problem of signal transduction.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Antibodies from combinatorial libraries use functional receptor pleiotropism to regulate cell fates
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

* Authors for correspondence: R. A. Lerner, Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Tel.: 858-784-8265; Fax: 858-784-2791; E-mail: rlerner@scripps.edu

References

Hide All
Barbas, C. F., Bain, J. D., Hoekstra, D. M. & Lerner, R. A. (1992). Semi-synthetic combinatorial antibody libraries: a chemical solution to the diversity problem. Proceeding of the National Academy of Sciences of the United States of America 89, 44574461.
Barbas, C. F., Kang, A. S., Lerner, R. A. & Benkovic, S. J. (1991). Assembly of combinatorial antibody libraries on phage surfaces: the gene III Site. Proceedings of the National Academy of Sciences of the United States of America 88, 79787982.
Hoogenboom, H. R., Griffiths, A. D., Johnson, K. S., Chiswell, D. J., Hudson, P. & Winter, G. (1991). Multi-subunit proteins on the surface of filamentous phage: methodologies for displaying antibody (Fab) heavy and light chains. Nucleic Acids Research 19, 41334137.
Hoogenboom, H. R. & Winter, G. (1992). By-passing immunization: human antibodies from synthetic repetoires of germline V h gene segments rearranged in vitro . Journal of Molecular Biology 227, 381388.
Huse, W. D., Sastry, L., Iverson, S. A., Kang, A. S., Alting-Mees, M., Burton, D. R., Benkovic, S. J. & Lerner, R. (1989). Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science 246, 12751281.
Kang, A. S., Barbas, C. F., Janda, K. D., Benkovic, S. J. & Lerner, R. A. (1991). Linkage of recognition and replication functions by assembling combinatorial antibody fab libraries along phage surfaces. Proceedings of the National Academy of Sciences of the United States of America 88, 43634366.
Lerner, R. A. (2006). Manufacturing immunity to disease in a test tube: the magic bullet realized. Angewandte Chemie International Edition in English 45, 81068125.
Lerner, R. A., Kang, A. S., Bain, J. D., Burton, D. R. & Barbas, C. F. (1992). Antibodies without immunization. Science 258, 13131314.
Marks, J. D., Hoogenboom, H. R., Bonnert, T. P., McCafferty, J., Griffiths, A. D. & Winter, G. (1991). By-passing immunization: human antibodies from V-gene libraries displayed on phage. Journal of Molecular Biology 222, 581597.
McCafferty, J., Griffiths, A. D., Winter, G. & Chiswell, D. J. (1990). Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348, 552554.
Orlandi, R., Güssow, D. H., Jones, P. T. & Winter, G. (1989). Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 86, 38333837.
Sastry, L., Alting-Mees, M., Huse, W. D., Short, J. M., Sorge, J. A., Hay, B. N., Janda, K. D., Benkovic, S. J. & Lerner, R. A. (1989). Cloning of the immunological repertoire in Escherichia Coli for generation of monoclonal catalytic antibodies: construction of a heavy chain variable region-specific cDNA library. Proceedings of the National Academy of Sciences of the United States of America 86, 57285732.
Xie, J., Yea, K., Zhang, H., Moldt, B., He, L., Zhu, J. & Lerner, R. A. (2014). Prevention of cell death by antibodies selected from intracellular combinatorial libraries. Chemistry and Biology 21, 274283.
Xie, J., Zhang, H., Yea, K. & Lerner, R. A. (2013). Autocrine signaling based selection of combinatorial antibodies that transdifferentiate human stem cells. Proceedings of the National Academy of Sciences of the United States of America 110, 80998104.
Yea, K., Xie, J., Zhang, H., Zhang, W. & Lerner, R. A. (2015). Selection of multiple agonist antibodies from intracellular combinatorial libraries reveals that cellular receptors are functionally pleiotropic. Current Opinion in Chemical Biology 26, 17.
Yea, K., Zhang, H., Xie, J., Jones, T. M., Yang, G., Song, B. D. & Lerner, R. A. (2013). Converting stem cells to dendritic cells by agonist antibodies from unbiased morphogenic selections. Proceedings of the National Academy of Sciences of the United States of America 110, 1496614971.
Zhang, H., Torkamani, A., Jones, T. M., Ruiz, D. I., Pons, J. & Lerner, R. A. (2011). Phenotype-information-phenotype cycle for deconvolution of combinatorial antibody libraries selected against complex systems. Proceedings of the National Academy of Sciences of the United States of America 108, 1345613461.
Zhang, H., Wilson, I. A., & Lerner, R. A. (2012). Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries. Proceedings of the National Academy of Sciences of the United States of America 109, 1572815733.
Zhang, H., Xie, J., & Lerner, R. A. (2014). A proximity based general method for identification of ligand and receptor interaction in living cells. Biochemical and Biophysical Research Communications 454, 251255.
Zhang, H., Yea, K., Xie, J., Ruiz, D., Wilson, I. A. & Lerner, R. A. (2013). Selecting agonists from single cells infected with combinatorial antibody libraries. Chemistry and Biology 20, 734741.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed