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. 1991 Jul;73(3):348–355.

Induction of anti-progesterone immunity and pregnancy blocking by anti-progesterone anti-idiotypes. Variable efficacy of polyclonal Ab2 antibodies directed against a panel of closely related Ab1 antibodies.

M W Wang 1, M J Sims 1, P R Symington 1, A S Humphreys 1, M J Taussig 1
PMCID: PMC1384554  PMID: 1908822

Abstract

Polyclonal rabbit anti-idiotypes (Ab2) have been raised against three mouse monoclonal antiprogesterone Ab1 antibodies (DB3, 11/32, 11/64) closely related in VH and VL sequences. The anti-idiotypes were characterized for specificity and used to immunize groups of female mice. The latter responded with production of anti-progesterone (Ab3) antibodies, confirming the ability of anti-idiotypes to mimic the immunogenicity of a steroid. The response to one of the anti-idiotypic reagents (anti-DB3-id) was 5-10 times stronger than those to the others, despite close sequence homology between the idiotypes. Moreover, immunization with anti-DB3-id led to a reduction in fertility rate from 90% (control) to 30%, whereas immunization with the other anti-idiotypes was without effect. Sequence and structural comparisons suggest that residues associated with VH CDR3 and VL CDR3 may have a key role in determining the efficiency of anti-idiotypic immunization against progesterone. The variability in outcome of using anti-idiotypic reagents against a defined panel of related antibodies is relevant to the use of anti-idiotypes as surrogate antigens.

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Selected References

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

  1. Berek C., Milstein C. Mutation drift and repertoire shift in the maturation of the immune response. Immunol Rev. 1987 Apr;96:23–41. doi: 10.1111/j.1600-065x.1987.tb00507.x. [DOI] [PubMed] [Google Scholar]
  2. Dalgleish A. G., Kennedy R. C. Anti-idiotypic antibodies as immunogens: idiotype-based vaccines. Vaccine. 1988 Jun;6(3):215–220. doi: 10.1016/0264-410x(88)90213-7. [DOI] [PubMed] [Google Scholar]
  3. Deverson E., Berek C., Taussig M., Feinstein A. Monoclonal BALB/c anti-progesterone antibodies use family IX variable region heavy chain genes. Eur J Immunol. 1987 Jan;17(1):9–13. doi: 10.1002/eji.1830170103. [DOI] [PubMed] [Google Scholar]
  4. Ellis S. T., Heap R. B., Butchart A. R., Rider V., Richardson N. E., Wang M. W., Taussig M. J. Efficacy and specificity of monoclonal antibodies to progesterone in preventing the establishment of pregnancy in the mouse. J Endocrinol. 1988 Jul;118(1):69–80. doi: 10.1677/joe.0.1180069. [DOI] [PubMed] [Google Scholar]
  5. Milstein C. P., Richardson N. E., Dieverson E. V., Feinstein A. Interchain disulphide bridges of mouse immunoglobulin M. Biochem J. 1975 Dec;151(3):615–624. doi: 10.1042/bj1510615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Misplon J. A., Reeves J. P., Harvath L., Rubinstein L. J., Epstein S. L. Induction of antigen-specific immunity with monoclonal anti-idiotypic antibodies in vivo: differences in potency and comparison of immunochemical properties. Eur J Immunol. 1989 Dec;19(12):2361–2365. doi: 10.1002/eji.1830191227. [DOI] [PubMed] [Google Scholar]
  7. Orlandi R., Güssow D. H., Jones P. T., Winter G. Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc Natl Acad Sci U S A. 1989 May;86(10):3833–3837. doi: 10.1073/pnas.86.10.3833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Phillips A., Hahn D. W., McGuire J., Wang M. W., Heap R. B., Rider V., Taussig M. J. Inhibition of pregnancy before and after implantation in rats with monoclonal antibody against progesterone. Contraception. 1988 Jul;38(1):109–116. doi: 10.1016/0010-7824(88)90100-x. [DOI] [PubMed] [Google Scholar]
  9. Potter M., Newell J. B., Rudikoff S., Haber E. Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol Immunol. 1982 Dec;19(12):1619–1630. doi: 10.1016/0161-5890(82)90273-5. [DOI] [PubMed] [Google Scholar]
  10. Rider V., Heap R. B. Heterologous anti-progesterone monoclonal antibody arrests early embryonic development and implantation in the ferret (Mustela putorius). J Reprod Fertil. 1986 Jan;76(1):459–470. doi: 10.1530/jrf.0.0760459. [DOI] [PubMed] [Google Scholar]
  11. Rider V., McRae A., Heap R. B., Feinstein A. Passive immunization against progesterone inhibits endometrial sensitization in pseudopregnant mice and has antifertility effects in pregnant mice which are reversible by steroid treatment. J Endocrinol. 1985 Jan;104(1):153–158. doi: 10.1677/joe.0.1040153. [DOI] [PubMed] [Google Scholar]
  12. Stura E. A., Arevalo J. H., Feinstein A., Heap R. B., Taussig M. J., Wilson I. A. Analysis of an anti-progesterone antibody: variable crystal morphology of the Fab' and steroid-Fab' complexes. Immunology. 1987 Dec;62(4):511–521. [PMC free article] [PubMed] [Google Scholar]
  13. Stura E. A., Feinstein A., Wilson I. A. Crystallization and preliminary crystallographic data for an antiprogesterone monoclonal antibody Fab' and steroid-Fab' complexes. J Mol Biol. 1987 Jan 5;193(1):229–231. doi: 10.1016/0022-2836(87)90642-5. [DOI] [PubMed] [Google Scholar]
  14. Taussig M. J., Brown N., Ellis S., Holliman A., Peat D., Richardson N., Heap R. B., Feinstein A. Anti-idiotypic sera against monoclonal anti-progesterone antibodies: production in rabbits and rats and characterization of specificity. Immunology. 1986 Jul;58(3):445–452. [PMC free article] [PubMed] [Google Scholar]
  15. Taussig M. J., Kirk D., Wang M. W., Ellis S., Meek K., Marvel J., Urbain J., Coombs R. R. Idiotype-anti-idiotype interactions of VHIX-coded anti-progesterone and anti-arsonate antibodies. Comparison of passive haemagglutination and radioimmunoassays. Scand J Immunol. 1987 Sep;26(3):267–276. doi: 10.1111/j.1365-3083.1987.tb02260.x. [DOI] [PubMed] [Google Scholar]
  16. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  17. Wang M. W., Heap R. B., Taussig M. J. Blocking of pregnancy in mice by immunization with anti-idiotype directed against monoclonal anti-progesterone antibody. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7098–7102. doi: 10.1073/pnas.86.18.7098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Winter E., Radbruch A., Krawinkel U. Members of novel VH gene families are found in VDJ regions of polyclonally activated B-lymphocytes. EMBO J. 1985 Nov;4(11):2861–2867. doi: 10.1002/j.1460-2075.1985.tb04015.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wright L. J., Feinstein A., Heap R. B., Saunders J. C., Bennett R. C., Wang M. Y. Progesterone monoclonal antibody blocks pregnancy in mice. Nature. 1982 Feb 4;295(5848):415–417. doi: 10.1038/295415a0. [DOI] [PubMed] [Google Scholar]

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