Phage antibodies: filamentous phage displaying antibody variable domains

Abstract

NEW ways of making antibodies have recently been demonstrated using gene technology. Immunoglobulm variable (V) genes are amplified from hybridomas or B cells using the polymerase chain reaction, and cloned into expression vectors. Soluble antibody fragments secreted from bacteria are then screened for binding activities (see ref. 1 for review). Screening of V genes would, however, be revolutionized if they could be expressed on the surface of bacteriophage. Phage carrying V genes that encode binding activities could then be selected directly with antigen. Here we show that complete antibody V domains can be displayed on the surface of fd bacteriophage, that the phage bind specifically to antigen and that rare phage (one in a million) can be isolated after affinity chromatography.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Winter, G. & Milstein, C. Nature (in the press).

  2. 2

    Amit, A. G., Mariuzza, R. A., Phillips, S. E. V. & Poljak, R. J. Science 233, 747–754 (1986).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Ward, E. S., Gussow, D., Griffiths, A. D., Jones, P. T. & Winter, G. Nature 341, 544–546 (1989).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Huston, J. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5879–5883 (1988).

    ADS  CAS  Article  Google Scholar 

  5. 5

    Kornberg, A. DNA Replication (Freeman, San Francisco, 1980).

    Google Scholar 

  6. 6

    Smith, G. Science 228, 1315–1317 (1985).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Parmley, S. F. & Smith, G. Gene 73, 305–318 (1988).

    CAS  Article  Google Scholar 

  8. 8

    Scott, J. K. & Smith, G. Science 249, 386–390 (1990).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Devlin, J. J., Panganiban, L. C. & Devlin, P. E. Science 249, 404–406 (1990).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Towbin, H., Staehelin, T. & Gordon, J. Proc. natn. Acad. Sci. U.S.A. 76, 4350–4354 (1979).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Laemmli, U. K. Nature 227, 680–685 (1970).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Harper, M., Lema, F., Boulot, G. & Poljak, R. J. Molec. Immun. 24, 97–108 (1987).

    CAS  Article  Google Scholar 

  13. 13

    Güssow, D. & Clackson, T. Nucleic Acids Res. 17, 4000 (1989).

    Article  Google Scholar 

  14. 14

    Orlandi, R., Güssow, D. H. & Jones, P. T. et al. Proc. natn. Acad. Sci. U.S.A. 86, 3833–3837 (1989).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Huse, W. D. et al. Science 246, 1275–1281 (1989).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Casali, P., Inghirami, G., Nakamura, M., Davies, T. F. & Notkins, A. L. Science 234, 476–479 (1986).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Milstein, C. Proc. R. Soc. B239, 1–16 (1990).

    ADS  Article  Google Scholar 

  18. 18

    Zacher, A. N., Stock, C. A., Golden, T. W. & Smith, G. P. Gene 9, 127–140 (1980).

    CAS  Article  Google Scholar 

  19. 19

    Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory, New York, 1989).

    Google Scholar 

  20. 20

    Taylor, J. W., Ott, J. & Eckstein, F. Nucleic Acids Res. 13, 8764–8785 (1985).

    Google Scholar 

  21. 21

    Goldsmith, M. E. & Konigsberg, W. H. Biochemistry 16, 2686–2694 (1977).

    CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

McCafferty, J., Griffiths, A., Winter, G. et al. Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348, 552–554 (1990). https://doi.org/10.1038/348552a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing