Advertisement

Modified antibodies

  • Richard Seabrook
  • Tony Atkinson

Abstract

Antibodies have proved themselves to be extremely versatile and sensitive reagents for the detection and quantitation of an analyte. This is partly because the mechanisms for generating antibody diversity ensure that an immense range of different chemical structures can be recognised, with exquisite specificity, by the antibody population. This allows the analyst to select an individual antigen-targeted antibody and use it to distinguish the antigen from a complex background of closely related structures. Furthermore, the recognition properties of the antibody can be readily coupled to a detection mechanism which can quantitatively signal antigen binding by the antibody. There are now a wide-range of different physical and chemical detection mechanisms which can be employed to produce such a signal.

Keywords

Disulphide Bond Antigen Binding Recombinant Antibody Antibody Molecule Amino Acid Modification 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Amit, A.G., Mariuzza, R.A., Philips, S.E.V., Poljak, R.J. (1986) Three dimensional structure of an antigen-antibody complex at 2.8Å resolution. Science. 233, 747–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Colman, P.M. (1988) Structure of antibody-antigen complexes: implications for immune recognition. Adv. Immunol. 43, 99–132.PubMedCrossRefGoogle Scholar
  3. 3.
    Brack, C., Hirama, M., Lenhard-Schuller, R., Tonegawa, S. (1978) A complete immunoglobulin gene is created by somatic recombination. Cell. 15, 1–14.PubMedCrossRefGoogle Scholar
  4. 4.
    Alt, W. (1986) Antibody diversity: New mechanism revealed. Nature. 322, 772–3.PubMedCrossRefGoogle Scholar
  5. 5.
    French, D.L., Laskov, R., Scharff, M.D. (1989) The role of somatic hypermutation in the generation of antibody diversity. Science. 244, 1152–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Reth, M., Gehrmann, P., Petrac, E., Wiese, P. (1986) A novel V H to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. Nature. 322, 840–2.PubMedCrossRefGoogle Scholar
  7. 7.
    Davies, D.R., Sheriff, S., Padlan, C.A. (1988) Antibody-antigen complexes. J. Biol. Chem. 263, 10541–4.PubMedGoogle Scholar
  8. 8.
    Muller, C.E. and Rajewsky, K. (1983) Isolation of immunoglobulin class switch variants from hybridoma lines secreting anti-idiotope antibodies by sequential sublining. J. Immunol. 131, 877–81.PubMedGoogle Scholar
  9. 9.
    Milstein, C. and Cuello, A.C. (1984) Hybrid hybridomas and the production of bi- specific monoclonal antibodies. Immunol. Today 5, 299–304.PubMedCrossRefGoogle Scholar
  10. 10.
    Spira, G., Bargellesi, A., Teillaud, J-L., Scharff, M.D. (1984) The identification of monoclonal class switch variants by Sib selection and an ELISA assay. J. Immunol. Meth. 74, 307–15.CrossRefGoogle Scholar
  11. 11.
    Aguilla, H.L., Pollock, R.R., Spira, G., Scharff, M.D. (1986) The production of more useful monoclonal antibodies. Immunol. Today 7, 380–3.CrossRefGoogle Scholar
  12. 12.
    Suresh, M.R., Cuello, A.C., Milstein, C. (1986) Bispecific monoclonal antibodies from hybridomas. Meth. Enzymol. 121, 210–28.PubMedCrossRefGoogle Scholar
  13. 13.
    Orlandi, R., Gussow, D.J., Jones, P.T., Winter, G. (1989) Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. P.N.A.S. 86, 3833–7.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Ward, E.S., Gussow, D., Griffiths, A.D., et al. (1989) Binding activities of a repertoire of single immunoglobulin variable domains secreted from Escherichia coli. Nature 341, 544–6.PubMedGoogle Scholar
  15. 15.
    Kriegler, M. (1990) Assembly of enhancers, promoters and splice signals to control expression of transfected genes. Meth. Enzymol. 185, 512–27.PubMedCrossRefGoogle Scholar
  16. 16.
    Sun, L.K., Curtis, P., Rekowicz-Szulcyznska, E., et al. (1987) Chimeric antibody with human constant regions and mouse variable region directed against carcinoma-associated antigen 17–1A. P.N.A.S. 84, 214–8.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Mulligan, R.C. and Berg, P. (1980) Expression of a bacterial gene in mammalian cells. Science. 209, 1422–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Atkinson, T., Barstow, D.A., Court, R.J., et al. (1986) High level microbial expression and purification of recombinant proteins. In Bioactive Microbial Products. (eds. Stowell, J.D., Bailey, P.J., Winstanley, D.J.) Vol 3, 27–43, Academic Press Inc., London.Google Scholar
  19. 19.
    Cabilly, S., Riggs, A.D., Pande, H., et al. (1984) Generation of antibody activity from immunoglobulin polypeptide chains produced in Escherichia coli. P.N.A.S. 81, 3273–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Wood, C.R., Boss, M.A., Kenten, J.H., et al. (1985) The synthesis and in vivo assembly of functional antibodies in yeast. Nature. 314, 466–49.Google Scholar
  21. 21.
    Wetzel, R. (1988) Active immunoglobulin fragments synthesised in E.coli—from Fab to Scantibodies. Prot. Eng. 2, 169–70.CrossRefGoogle Scholar
  22. 22.
    Better, M., Chang, C.P., Robinson, R.R., Horwitz, H.H. (1988) Escherichia coli secretion of an active chimeric antibody fragment. Science. 240, 1041–3.PubMedCrossRefGoogle Scholar
  23. 23.
    Skerra, A. and Pluckthun, A. (1988) Assembly of a functional Fv fragment in E. Coli. Science. 240, 1038–40.PubMedGoogle Scholar
  24. 24.
    Goloubinoff, P., Gatenby, A.A., Lorimer, G.H. (1989) GroE heat-shock proteins promote assembly of foreign prokaryotic ribulose biphosphate carboxylase oligomers in Escherichia coli. Nature. 337, 44–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Better, M. and Horwitz, A.H. (1989) Expression of engineered antibodies and antibody fragments in microorganisms. Meth. Enzymol. 178, 476–96.PubMedCrossRefGoogle Scholar
  26. 26.
    Morrison, S. and Oi, V.T. (1989) Genetically engineered antibody molecules. Adv. Immunol. 44, 65–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Huse, W.D., Sastry, L., Iverson, S.A., et al. (1989) Generation of a large combinatorial library of the immunoglobulin repertoire in phage lambda. Science. 246, 1275–81.PubMedCrossRefGoogle Scholar
  28. 28.
    Dangl, J.L., Wensel, T.G., Morrison, S.L., et al. (1988) Segmental flexibility and compliment fixation of genetically engineered chimeric human, rabbit and mouse antibody. EMBO Journal 7, 1989–94.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Riechmann, L., Clark, M., Waldmann, H., Winter, G. (1988) Reshaping human antibodies for therapy. Nature 332, 323–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Neuberger, M.S., Williams, G.T., Fox, R.O. (1984) Recombinant antibodies possessing novel effector functions. Nature 312, 604–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Chaudhary, V.K., Queen, C., Junghams, R.P., et al. (1989) A recombinant immunotoxin consisting of two antibody variable domains fused to pseudomonas exotoxin. Nature 339, 394–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Verhoeyen, M., Milstein, C., Winter, G. (1988) Reshaping human antibodies; grafting an antilysozyme activity. Science 239, 1534–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Chothia, C. and Lesk, A. (1987) Canonical structures for the hypervariable regions of immunoglobulins. J. Mol. Biol. 196, 901–17.PubMedCrossRefGoogle Scholar
  34. 34.
    Blundell, T.L. Sibanda, B.L., Sternberg, M.J.E., Thornton, J.M. (1987) Knowledge-based prediction of protein structures and the design of novel molecules. Nature 326, 347–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Webster, D.M., Roberts,S., Cheetham, J.C., et al. (1988) Engineering antibody affinity and specificity. Int. J. Cancer: Suppl. 3, 13–16.CrossRefGoogle Scholar
  36. 36.
    Davies, D.R. and Padland, E.A. (1990) Antibody-antigen complexes. Ann. Rev. Biochem. 59, 439–73.PubMedCrossRefGoogle Scholar
  37. 37.
    Bruccoleri, R.E., Haber, E., Novotony, J. (1988) Structure of antibody hypervariable loops reproduced by a conformational search algorithm. Nature. 335, 564–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Kussie, P.H., Sherman, M.A., Marchetti, D., Linthicum, D.S. (1989) Molecular analysis of monoclonal idiotypes and anti-idiotypes. Meth. Enzymol. 178, 91–107.PubMedCrossRefGoogle Scholar
  39. 39.
    de la Paz, P., Sutton, B.J., Darsley, M.J., Rees, A.R. (1986) Modelling of the combining sites of three anti-lysozyme monoclonal antibodies and of the complex between one of the antibodies and its epitope. EMBO Journal 5, 415–25.Google Scholar
  40. 40.
    Holm, L., Leaksonen, L., Kaartinen, M., et al. (1990) Molecular modelling study of antigen binding to oxazolone-specific antibodies: the Oxl idotypic IgG and its mature variant with increased affinity to 2-phenyloxazalone. Prot. Eng. 3, 403–9.CrossRefGoogle Scholar
  41. 41.
    Roberts, S., Cheetham, J.C., Rees, A.R. (1987) Generation of an antibody with enhanced affinity and specificity for its antigen by protein engineering. Nature. 328, 731–4.PubMedCrossRefGoogle Scholar
  42. 42.
    Allen, D., Simon, T., Sablitzky, F., et al. (1988) Antibody engineering for the analysis of affinity maturation of an anti-hapten response. EMBO Journal. 7, 1995–2001.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Getzoff, E.D., Tainer, J.A., Lerner, R.A., Geysen, M. (1988) The chemistry and mechanism of antibody binding to protein antigens. Adv. Immunol. 43, 1–98.PubMedCrossRefGoogle Scholar
  44. 44.
    Van Regenmortel, M.H.V. (1989) Structural and functional approaches to the study pf protein antigenicity. Immunol. Today 10, 266–72.PubMedCrossRefGoogle Scholar
  45. 45.
    Winter, G.P. (1989) Antibody engineering. Phil. Trans. R. Soc. Lond. B 324, 537–47.CrossRefGoogle Scholar
  46. 46.
    Lerner, R.A. and Tramontano, D.S. (1987) Antibodies as enzymes. TIBS. 12, 427–30.Google Scholar
  47. 47.
    Green, B.B.S. and Tawfik, D.S. (1989) Catalytic antibodies: tailor-made-enzyme-like catalysts for chemical reaction. T.I.Biotech. 7, 304–10.CrossRefGoogle Scholar

Copyright information

© Palgrave Macmillan, a division of Macmillan Publishers Limited 1991

Authors and Affiliations

  • Richard Seabrook
  • Tony Atkinson

There are no affiliations available

Personalised recommendations