Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 May 15;88(10):4363–4366. doi: 10.1073/pnas.88.10.4363

Linkage of recognition and replication functions by assembling combinatorial antibody Fab libraries along phage surfaces.

A S Kang 1, C F Barbas 1, K D Janda 1, S J Benkovic 1, R A Lerner 1
PMCID: PMC51659  PMID: 1903540

Abstract

We describe a method based on a phagemid vector with helper phage rescue for the construction and rapid analysis of combinatorial antibody Fab libraries. This approach should allow the generation and selection of many monoclonal antibodies. Antibody genes are expressed in concert with phage morphogenesis, thereby allowing incorporation of functional Fab molecules along the surface of filamentous phage. The power of the method depends upon the linkage of recognition and replication functions and is not limited to antibody molecules.

Full text

PDF
4363

Images in this article

4364Image
on p.4364
4365Image
on p.4365
4365Image
on p.4365

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bass S., Greene R., Wells J. A. Hormone phage: an enrichment method for variant proteins with altered binding properties. Proteins. 1990;8(4):309–314. doi: 10.1002/prot.340080405. [DOI] [PubMed] [Google Scholar]
  2. Better M., Chang C. P., Robinson R. R., Horwitz A. H. Escherichia coli secretion of an active chimeric antibody fragment. Science. 1988 May 20;240(4855):1041–1043. doi: 10.1126/science.3285471. [DOI] [PubMed] [Google Scholar]
  3. Boss M. A., Kenten J. H., Wood C. R., Emtage J. S. Assembly of functional antibodies from immunoglobulin heavy and light chains synthesised in E. coli. Nucleic Acids Res. 1984 May 11;12(9):3791–3806. doi: 10.1093/nar/12.9.3791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cabilly S., Riggs A. D., Pande H., Shively J. E., Holmes W. E., Rey M., Perry L. J., Wetzel R., Heyneker H. L. Generation of antibody activity from immunoglobulin polypeptide chains produced in Escherichia coli. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3273–3277. doi: 10.1073/pnas.81.11.3273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Caton A. J., Koprowski H. Influenza virus hemagglutinin-specific antibodies isolated from a combinatorial expression library are closely related to the immune response of the donor. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6450–6454. doi: 10.1073/pnas.87.16.6450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chang C. N., Model P., Blobel G. Membrane biogenesis: cotranslational integration of the bacteriophage f1 coat protein into an Escherichia coli membrane fraction. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1251–1255. doi: 10.1073/pnas.76.3.1251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chiang Y. L., Sheng-Dong R., Brow M. A., Larrick J. W. Direct cDNA cloning of the rearranged immunoglobulin variable region. Biotechniques. 1989 Apr;7(4):360–366. [PubMed] [Google Scholar]
  8. Cwirla S. E., Peters E. A., Barrett R. W., Dower W. J. Peptides on phage: a vast library of peptides for identifying ligands. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6378–6382. doi: 10.1073/pnas.87.16.6378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Devlin J. J., Panganiban L. C., Devlin P. E. Random peptide libraries: a source of specific protein binding molecules. Science. 1990 Jul 27;249(4967):404–406. doi: 10.1126/science.2143033. [DOI] [PubMed] [Google Scholar]
  10. Huse W. D., Sastry L., Iverson S. A., Kang A. S., Alting-Mees M., Burton D. R., Benkovic S. J., Lerner R. A. Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science. 1989 Dec 8;246(4935):1275–1281. doi: 10.1126/science.2531466. [DOI] [PubMed] [Google Scholar]
  11. Janda K. D., Schloeder D., Benkovic S. J., Lerner R. A. Induction of an antibody that catalyzes the hydrolysis of an amide bond. Science. 1988 Sep 2;241(4870):1188–1191. doi: 10.1126/science.3413482. [DOI] [PubMed] [Google Scholar]
  12. Larrick J. W., Danielsson L., Brenner C. A., Abrahamson M., Fry K. E., Borrebaeck C. A. Rapid cloning of rearranged immunoglobulin genes from human hybridoma cells using mixed primers and the polymerase chain reaction. Biochem Biophys Res Commun. 1989 May 15;160(3):1250–1256. doi: 10.1016/s0006-291x(89)80138-x. [DOI] [PubMed] [Google Scholar]
  13. McCafferty J., Griffiths A. D., Winter G., Chiswell D. J. Phage antibodies: filamentous phage displaying antibody variable domains. Nature. 1990 Dec 6;348(6301):552–554. doi: 10.1038/348552a0. [DOI] [PubMed] [Google Scholar]
  14. Mullinax R. L., Gross E. A., Amberg J. R., Hay B. N., Hogrefe H. H., Kubitz M. M., Greener A., Alting-Mees M., Ardourel D., Short J. M. Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage lambda immunoexpression library. Proc Natl Acad Sci U S A. 1990 Oct;87(20):8095–8099. doi: 10.1073/pnas.87.20.8095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Orlandi R., Güssow D. H., Jones P. T., Winter G. Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 May;86(10):3833–3837. doi: 10.1073/pnas.86.10.3833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Parmley S. F., Smith G. P. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene. 1988 Dec 20;73(2):305–318. doi: 10.1016/0378-1119(88)90495-7. [DOI] [PubMed] [Google Scholar]
  17. Persson M. A., Caothien R. H., Burton D. R. Generation of diverse high-affinity human monoclonal antibodies by repertoire cloning. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2432–2436. doi: 10.1073/pnas.88.6.2432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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. Cloning of the immunological repertoire in Escherichia coli for generation of monoclonal catalytic antibodies: construction of a heavy chain variable region-specific cDNA library. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5728–5732. doi: 10.1073/pnas.86.15.5728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scott J. K., Smith G. P. Searching for peptide ligands with an epitope library. Science. 1990 Jul 27;249(4967):386–390. doi: 10.1126/science.1696028. [DOI] [PubMed] [Google Scholar]
  20. Skerra A., Plückthun A. Assembly of a functional immunoglobulin Fv fragment in Escherichia coli. Science. 1988 May 20;240(4855):1038–1041. doi: 10.1126/science.3285470. [DOI] [PubMed] [Google Scholar]
  21. Ward E. S., Güssow D., Griffiths A. D., Jones P. T., Winter G. Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature. 1989 Oct 12;341(6242):544–546. doi: 10.1038/341544a0. [DOI] [PubMed] [Google Scholar]
  22. Winter G., Milstein C. Man-made antibodies. Nature. 1991 Jan 24;349(6307):293–299. doi: 10.1038/349293a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES