Restructuring Enzymes and Antibodies

  • Greg Winter
  • Michael Neuberger
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 15B)


It has recently become possible to introduce DNA into lymphoid cell lines [1–3]. By constructing lines which are stably transfected with immunoglobulin gene DNA, it is possible to direct the synthesis and secretion in good yield of antibody (Ab) molecules that display specific desired characteristics. Thus, exon shuffling can be used to direct the production of chimaeric Ab’s in which mouse-encoded antigen-specific variable regions are joined to human constant regions. In this way, a line secreting a chimaeric IgE Ab has been established where the Cε constant region is of human origin (thus allowing binding to human mast cells) and the variable regions are of mouse origin and form a binding site for the hapten 4-hydroxy-3-nitrophenylacetyl [4]. In other experiments, gene fusions have been performed to make a recombinant Ab in which the Fc portion of the Ab is replaced with an active enzyme moiety (staphylococcal nuclease), thus showing that this is a viable approach for making Ab’s exhibiting novel effector functions [5].


Constant Region Viable Approach Human Mast Cell tRNA Synthetase Lymphoid Cell Line 
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.


  1. 1.
    Neuberger, M.S. (1983) EMBO J. 2, 1370–1378.Google Scholar
  2. 2.
    Oi, V.T., Morrison, S.L., Herzenberg, L.A. & Berg, P. (1983) Proc. Nat. Acad. Sci. 80, 825–829.CrossRefGoogle Scholar
  3. 3.
    Ochi, A., Hawley, R.G., Hawley, M.J., Shulman, A., Traunecker, J., Köhler, G. & Hozumi, N. (1983) Proc. Nat. Acad. Sci. 80, 6351–6355.CrossRefGoogle Scholar
  4. 4.
    Neuberger, M.S., Williams, G.T., Mitchell, E.B., Jouhal, S.S., Flanagan, J.G. & Rabbitts, T.H. (1985) Nature 314, 268–270.CrossRefGoogle Scholar
  5. 5.
    Neuberger, M.S., Williams, G.T. & Fox, R.O. (1984) Nature 312, 604–608.CrossRefGoogle Scholar
  6. 6.
    Winter, G., Fersht, A.R., Wilkinson, A.J., Zoller, M.J. & Smith, M. (1982) Nature 299, 756–758.CrossRefGoogle Scholar
  7. 7.
    Wilkinson, A.J., Fersht, A.R., Blow, D.M. & Winter, G. (1983) Biochemistry 22, 3581–3586.CrossRefGoogle Scholar
  8. 8.
    Wilkinson, A.J., Fersht, A.R., Blow, D.M., Carter, P. & Winter, G. (1984) Nature 307, 187–188.CrossRefGoogle Scholar
  9. 9.
    Carter, P., Winter, G., Wilkinson, A.J. & Fersht, A.R. (1984) Cell, 38, 835–840.CrossRefGoogle Scholar
  10. 10.
    Fersht, A.R., Shi, J.-P., Knill-Jones, J., Lowe, D.M., Wilkinson, A.J., Blow, D.M., Brick, P., Carter, P., Waye, M.M.Y. & Winter, G. (1985) Nature 314, 235–238.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Greg Winter
    • 1
  • Michael Neuberger
    • 1
  1. 1.MRC Laboratory of Molecular BiologyCambridgeUK

Personalised recommendations