Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1971 Sep 1;134(3):751–764. doi: 10.1084/jem.134.3.751

ANTIBODY-MEDIATED ACTIVATION OF A DEFECTIVE β-D-GALACTOSIDASE

II. IMMUNOLOGICAL RELATIONSHIP BETWEEN THE NORMAL AND THE DEFECTIVE ENZYME

Franco Celada 1, John Ellis 1, Kerstin Bodlund 1, Boris Rotman 1
PMCID: PMC2139083  PMID: 15776573

Abstract

Two closely related protein antigens were used to study immunogenic competition. Namely, normal β-D-galactosidase of Escherichia coli (Z) and a genetically defective β-D-galactosidase (AMEF) which seems to differ from the normal in one amino acid substitution. A unique characteristic of this pair of antigens is that, although they are indistinguishable in precipitation and absorption tests with antibodies, the enzymatic activity of AMEF is specifically increased several-hundredfold in the presence of antibodies directed against Z. The following results show that Z and AMEF also differ in their immunogenic ability: (a) antibodies directed against Z activated AMEF; antibodies directed against AMEF did not activate, but competed specifically with activating antibodies. (b) Animals immunized with AMEF failed to produce activating antibodies when they were subsequently challenged with Z, although the presence of some cells primed to produce activating antibodies could be demonstrated by adoptive transfer. (c) Animals preimmunized with Z were stimulated in their production of activating antibodies by AMEF challenge, although not as efficiently as with Z. A model explaining these observations by competition for the immunogenic site among antigen-sensitive cells carrying cross-reacting receptors is presented.

Full Text

The Full Text of this article is available as a PDF (812.1 KB).

Selected References

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

  1. Avrameas S., Bouteille M. Ultrastructural localization of antibody by antigen label with peroxidase. Exp Cell Res. 1968 Oct;53(1):166–176. doi: 10.1016/0014-4827(68)90364-9. [DOI] [PubMed] [Google Scholar]
  2. Avrameas S., Leduc E. H. Detection of simultaneous antibody synthesis in plasma cells and specialized lymphocytes in rabbit lymph nodes. J Exp Med. 1970 Jun 1;131(6):1137–1168. doi: 10.1084/jem.131.6.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CINADER B., LAFFERTY K. J. MECHANISM OF ENZYME INHIBITION BY ANTIBODY. A STUDY OF THE NEUTRALIZATION OF RIBONUCLEASE. Immunology. 1964 Jul;7:342–362. [PMC free article] [PubMed] [Google Scholar]
  4. COOK A., LEDERBERG J. Recombination studies of lactose nonfermenting mutants of Escherichia coli K-12. Genetics. 1962 Oct;47:1335–1353. doi: 10.1093/genetics/47.10.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CRAVEN G. R., STEERS E., Jr, ANFINSEN C. B. PURIFICATION, COMPOSITION, AND MOLECULAR WEIGHT OF THE BETA-GALACTOSIDASE OF ESCHERICHIA COLI K12. J Biol Chem. 1965 Jun;240:2468–2477. [PubMed] [Google Scholar]
  6. Celada F. Quantitative studies of the adoptive immunological memory in mice. I. An age-dependent barrier to syngeneic transplantation. J Exp Med. 1966 Jul 1;124(1):1–14. doi: 10.1084/jem.124.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Davis B. D. The Isolation of Biochemically Deficient Mutants of Bacteria by Means of Penicillin. Proc Natl Acad Sci U S A. 1949 Jan;35(1):1–10. doi: 10.1073/pnas.35.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eisen H. N., Little J. R., Steiner L. A., Simms E. S., Gray W. Degeneracy in the secondary immune response: stimulation of antibody formation by cross-reacting antigens. Isr J Med Sci. 1969 May-Jun;5(3):338–351. [PubMed] [Google Scholar]
  9. Fowler A. V., Zabin I. Co-linearity of beta-galactosidase with its gene by immunological detection of incomplete polypeptide chains. Science. 1966 Nov 25;154(3752):1027–1029. doi: 10.1126/science.154.3752.1027. [DOI] [PubMed] [Google Scholar]
  10. LINDSLEY D. L., ODELL T. T., Jr, TAUSCHE F. G. Implantation of functional erythropoietic elements following total-body irradiation. Proc Soc Exp Biol Med. 1955 Nov;90(2):512–515. doi: 10.3181/00379727-90-22082. [DOI] [PubMed] [Google Scholar]
  11. Leduc E. H., Scott G. B., Avrameas S. Ultrastructural localization of intracellular immune globulins in plasma cells and lymphoblasts by enzyme-labeled antibodies. J Histochem Cytochem. 1969 Apr;17(4):211–224. doi: 10.1177/17.4.211. [DOI] [PubMed] [Google Scholar]
  12. MITCHISON N. A. INDUCTION OF IMMUNOLOGICAL PARALYSIS IN TWO ZONES OF DOSAGE. Proc R Soc Lond B Biol Sci. 1964 Dec 15;161:275–292. doi: 10.1098/rspb.1964.0093. [DOI] [PubMed] [Google Scholar]
  13. Messerw, Melchers F. Genetic analysis of mutants producing defective beta-galactosidase which can be activated by specific antibodie. Mol Gen Genet. 1970;109(2):152–161. doi: 10.1007/BF00269651. [DOI] [PubMed] [Google Scholar]
  14. Newton W. A., Beckwith J. R., Zipser D., Brenner S. Nonsense mutants and polarity in the lac operon of Escherichia coli. J Mol Biol. 1965 Nov;14(1):290–296. doi: 10.1016/s0022-2836(65)80250-9. [DOI] [PubMed] [Google Scholar]
  15. POLLOCK M. R. Penicillinase-antipenicillinase. Ann N Y Acad Sci. 1963 May 8;103:989–1005. doi: 10.1111/j.1749-6632.1963.tb53750.x. [DOI] [PubMed] [Google Scholar]
  16. ROTMAN B. Measurement of activity of single molecules of beta-D-galactosidase. Proc Natl Acad Sci U S A. 1961 Dec 15;47:1981–1991. doi: 10.1073/pnas.47.12.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rotman M. B., Celada F. Antibody-mediated activation of a defective beta-D-galactosidase extracted from an Escherichia coli mutant. Proc Natl Acad Sci U S A. 1968 Jun;60(2):660–667. doi: 10.1073/pnas.60.2.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. SUSKIND S. R., WICKHAM M. L., CARSIOTIS M. Antienzymes in immunogenetic studies. Ann N Y Acad Sci. 1963 May 8;103:1106–1127. doi: 10.1111/j.1749-6632.1963.tb53762.x. [DOI] [PubMed] [Google Scholar]
  19. Schechter B., Schechter I., Ramachandran J., Conway-Jacobs A., Sela M. The synthesis and circular dichroism of a series of peptides possessing the structure (L-tyrosyl-L-alanyl-L-glutamyl)n. Eur J Biochem. 1971 Jun 11;20(3):301–308. doi: 10.1111/j.1432-1033.1971.tb01394.x. [DOI] [PubMed] [Google Scholar]
  20. Schechter B., Schechter I., Sela M. Antibody combining sites to a series of peptide determinants of increasing size and defined structure. J Biol Chem. 1970 Mar 25;245(6):1438–1447. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES