Antibody-Mediated Activation of Genetically Defective Escherichia Coli Galactosidases by Monoclonal Antibodies

  • Roberto S. Accolla
  • Renata Cina’
  • Elisabetta Montesoro
  • Franco Celada

Abstract

The effects of antibody binding on protein conformation can be dramatic, and some examples have been known for several years. A great deal of information has been gathered recently from Escherichia coli β-galactosidase, a tetrameric enzyme of Mr 465,000 composed of four identical subunits. By using wild-type enzyme and a battery of mutant products first as immunogens and then as antigens in a series of serological reactions, a number of “conformational effects” have been discovered in this system1. These include (a) protection from thermal denaturation; (b) activation of defective enzyme; (c) facilitation of complementation between deletion products; and (d) inactivation of native enzyme. Apparently, with the exception of the first one, in which the antigen and the immunogen used to raise antibody are identical and the immune interaction stabilizes the conformation of the antigen molecule, all other cases involve a change in the tertiary or quaternary conformation of the enzyme. Such a mechanism may require antibodies directed toward conformation dependent determinants which are capable of interacting with these determinants even when the molecular conformation is modified, or unstable.

Keywords

Assimilation 

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References

  1. 1.
    F. Celada and R. Strom, Antibody-induced conformation changes, Quart.Rev.of Biophysics. 5:(3)395–425 (1972).CrossRefGoogle Scholar
  2. 2.
    G. Kohler, Frequency of precursor cells against the enzyme β-galactosidase. An estimate of the BALB/c strain antibody repertoire, Eur.J.Immunol. 6:340–346 (1976).PubMedCrossRefGoogle Scholar
  3. 3.
    R.S. Accolla and F. Celada, Immune responses against the β-galactosidase enzyme of E. coli at precursor cell level. I. Analysis of the secondary repertoire in BALB/c mice, Eur.J. Immunol. 8:688–696 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    F. Celada, A.V. Fowler, and I. Zabin, Probes of β-galactosidase structure with antibodies. Reaction of anti-peptide antibodies against native enzyme, Biochemistry 17:5156–5160 (1978).PubMedCrossRefGoogle Scholar
  5. 5.
    F. Conway De Macario, J. Ellis, R. Guzman, and M.B. Rotman, Antibody mediated activation of a defective β-galactosidase: Divµ form of the activable mutant enzyme, PNAS, USA. 75:720–724 (1978).CrossRefGoogle Scholar
  6. 6.
    A.R. Frackelton and M.B. Rotman, Functional diversity of antibodies elicited by bacterial β-D. galactosidase; monoclonal activating, inactivating, protecting and null antibodies to normal enzyme, J.Biol.Chem. 255:5286 (1980).PubMedGoogle Scholar
  7. 7.
    R.S. Accolla, R. Cina, E. Montesoro, and F. Celada, Antibody mediated activation of genetically defective E. coli β-galactosidases by monoclonal antibodies induced by somatic cell hybrids, PNAS.USA. 78:2478 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Roberto S. Accolla
    • 1
    • 2
  • Renata Cina’
    • 1
    • 2
  • Elisabetta Montesoro
    • 1
    • 2
  • Franco Celada
    • 1
    • 2
  1. 1.Lausanne BranchLudwig Institute for Cancer ResearchEpalingesSwitzerland
  2. 2.Università di GenovaGenovaItaly

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