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. 1973 Oct 31;138(5):1248–1265. doi: 10.1084/jem.138.5.1248

IDIOTYPIC SPECIFICITY OF RABBIT ANTIBODIES TO STREPTOCOCCAL GROUP POLYSACCHARIDES

Dietmar G Braun 1, Andrew S Kelus 1
PMCID: PMC2139431  PMID: 4200777

Abstract

Anti-idiotypic antisera against six restricted rabbit streptococcal group specific antibodies have been raised in rabbits matched for allotypes. All these antisera reacted specifically with their homologous idiotypes on double-diffusion tests in agarose gel. In addition, they showed a high incidence of cross-specificities with group-specific hyperimmune sera induced in both closely related and unrelated individuals. These precipitating cross-specificities could be explained for two systems by the interference of rheumatoid factor. Two idiotypic antibody systems have been analyzed in detail; these were restricted antibodies produced in a father and in one of his offspring. The methods employed included binding inhibition of radio-labeled homologous Fab fragments and hemagglutination inhibition with homologous idiotypic coat. The data demonstrated that only related rabbits produced, besides non-cross-reacting antibodies, idiotypically similar antibodies raised to the same antigen. About one-third of the cross-reactive idiotypes showed binding inhibition between 31 and 92%. Inhibition of binding above 50% in the paternal idiotypic system was only achieved by one offspring antibody whereas the F1 progeny idiotypic system was inhibited to this extent by seven antibodies of related rabbits. In contrast, 87.5% and 91.7% of antibodies of unrelated rabbits were less than 20% inhibitory. Within this study two idiotypically identical antibodies have not been found. This implies that A-variant-specific antibodies of related rabbits which produced antipolysaccharide antibodies were structurally different. Cross-reaction, even if greater than 90% by binding inhibition, appears to involve only part and not all of the variable regions.

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Selected References

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  1. AHO K., WAGER O. Production of anti-antibodies in rabbits. Ann Med Exp Biol Fenn. 1961;39:79–87. [PubMed] [Google Scholar]
  2. Blomberg B., Geckeler W. R., Weigert M. Genetics of the antibody response to dextran in mice. Science. 1972 Jul 14;177(4044):178–180. doi: 10.1126/science.177.4044.178. [DOI] [PubMed] [Google Scholar]
  3. Bokisch V. A., Bernstein D., Krause R. M. Occurrence of 19S and 7S anti-IgGs during hyperimmunization of rabbits with streptococci. J Exp Med. 1972 Oct 1;136(4):799–815. doi: 10.1084/jem.136.4.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyer S. H. Extraordinary incidence of electrophoretically silent genetic polymorphisms. Nature. 1972 Oct 20;239(5373):453–454. doi: 10.1038/239453a0. [DOI] [PubMed] [Google Scholar]
  5. Braun D. G., Eichmann K., Krause R. M. Rabbit antibodies to streptococcal carbohydrates. Influence of primary and secondary immunization and of possible genetic factors on the antibody response. J Exp Med. 1969 Apr 1;129(4):809–830. doi: 10.1084/jem.129.4.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Braun D. G., Jaton J. C. The aminoterminal sequence of antibody light chains: evidence for possible inheritance of structural genes. Immunochemistry. 1973 Jun;10(6):387–395. doi: 10.1016/0019-2791(73)90090-6. [DOI] [PubMed] [Google Scholar]
  7. Braun D. G., Kjems E., Cramer M. A rabbit family of restricted high responders to the streptococcal group A-variant polysaccharide. Selective breeding narrows the isoelectric focusing spectra of dominant clones. J Exp Med. 1973 Sep 1;138(3):645–658. doi: 10.1084/jem.138.3.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Braun D. G., Krause R. M. The individual antigenic specificity of antibodies to streptococcal carbohydrates. J Exp Med. 1968 Nov 1;128(5):969–989. doi: 10.1084/jem.128.5.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Briles D. E., Krause R. M. Mouse antibodies to group A streptococcal carbohydrate; use of idiotypy to detect inbred strain specificity and to monitor spleen cell transfer in syngenetic mice. J Immunol. 1972 Dec;109(6):1311–1320. [PubMed] [Google Scholar]
  10. CHRISTIAN C. L. RHEUMATOID FACTOR PROPERTIES OF HYPERIMMUNE RABBIT SERA. J Exp Med. 1963 Nov 1;118:827–844. doi: 10.1084/jem.118.5.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carson D., Weigert M. Immunochemical analysis of the cross-reacting idiotypes of mouse myeloma proteins with anti-dextran activity and normal anti-dextran antibody. Proc Natl Acad Sci U S A. 1973 Jan;70(1):235–239. doi: 10.1073/pnas.70.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eichmann K., Braun D. G., Feizi T., Krause R. M. The emergence of antibodies with either identical or unrelated individual antigenic specificity during repeated immunizations with streptococcal vaccines. J Exp Med. 1970 Jun 1;131(6):1169–1189. doi: 10.1084/jem.131.6.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Eichmann K., Braun D. G., Krause R. M. Influence of genetic factors on the magnitude and the heterogeneity of the immune response in the rabbit. J Exp Med. 1971 Jul 1;134(1):48–65. doi: 10.1084/jem.134.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Eichmann K. Idiotype expression and the inheritance of mouse antibody clones. J Exp Med. 1973 Mar 1;137(3):603–621. doi: 10.1084/jem.137.3.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Eichmann K. Idiotypic identity of antibodies to streptococcal carbohydrate in inbred mice. Eur J Immunol. 1972 Aug;2(4):301–307. doi: 10.1002/eji.1830020402. [DOI] [PubMed] [Google Scholar]
  16. Eichmann K., Kindt T. J. The inheritance of individual antigenic specificities of rabbit antibodies to streptococcal carbohydrates. J Exp Med. 1971 Aug 1;134(2):532–552. doi: 10.1084/jem.134.2.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. GREY H. M., MANNIK M., KUNKEL H. G. INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS. J Exp Med. 1965 Apr 1;121:561–575. doi: 10.1084/jem.121.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gold E. R., Fudenberg H. H. Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol. 1967 Nov;99(5):859–866. [PubMed] [Google Scholar]
  19. Hopper J. E., MacDonald A. B., Nisonoff A. Quantitative investigations of idiotypic antibodies. II. Nonprecipitating antibodies. J Exp Med. 1970 Jan 1;131(1):41–56. doi: 10.1084/jem.131.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hunter R. Standardization of the chloramine-T method of protein iodination. Proc Soc Exp Biol Med. 1970 Mar;133(3):989–992. doi: 10.3181/00379727-133-34611. [DOI] [PubMed] [Google Scholar]
  21. KRAUSE R. M., McCARTY M. Studies on the chemical structure of the streptococcal cell wall. II. The composition of group C cell walls and chemical basis for serologic specificity of the carbohydrate moiety. J Exp Med. 1962 Jan 1;115:49–62. doi: 10.1084/jem.115.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kelus A. S., Gell P. G. Immunoglobulin allotypes of experimental animals. Prog Allergy. 1967;11:141–184. [PubMed] [Google Scholar]
  23. Kelus A. S., Gell P. G. Immunological analysis of rabbit anti-antibody systems. J Exp Med. 1968 Jan 1;127(1):215–234. doi: 10.1084/jem.127.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kindt T. J., Klapper D. G., Waterfield M. D. An idiotypic cross-reaction between allotype a3 and allotype a negative rabbit antibodies to streptococcal carbohydrate. J Exp Med. 1973 Mar 1;137(3):636–648. doi: 10.1084/jem.137.3.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kindt T. J., Seide R. K., Bokisch V. A., Krause R. M. Detection of idiotypic cross-reactions among streptococcal antisera from related rabbits. J Exp Med. 1973 Sep 1;138(3):522–537. doi: 10.1084/jem.138.3.522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kuettner M. G., Wang A. L., Nisonoff A. Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains. J Exp Med. 1972 Mar 1;135(3):579–595. doi: 10.1084/jem.135.3.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kunkel H. G., Agnello V., Joslin F. G., Winchester R. J., Capra J. D. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity. J Exp Med. 1973 Feb 1;137(2):331–342. doi: 10.1084/jem.137.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kunkel H. G. Experimental approaches tohomogenous antibody populations. iIndividual antigenic specificity, cross specificity and diversity of human antibodies. Fed Proc. 1970 Jan-Feb;29(1):55–58. [PubMed] [Google Scholar]
  29. Kunkel H. G., Mannik M., Williams R. C. Individual Antigenic Specificity of Isolated Antibodies. Science. 1963 Jun 14;140(3572):1218–1219. doi: 10.1126/science.140.3572.1218. [DOI] [PubMed] [Google Scholar]
  30. NISONOFF A., WISSLER F. C., LIPMAN L. N., WOERNLEY D. L. Separation of univalent fragments from the bivalent rabbit antibody molecule by reduction of disulfide bonds. Arch Biochem Biophys. 1960 Aug;89:230–244. doi: 10.1016/0003-9861(60)90049-7. [DOI] [PubMed] [Google Scholar]
  31. Oudin J., Bordenave G. Observations on idiotypy of rabbit antibodies against Salmonella abortus-equi. Nat New Biol. 1971 May 19;231(20):86–87. doi: 10.1038/newbio231086a0. [DOI] [PubMed] [Google Scholar]
  32. Oudin J., Cazenave P. A. Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function. Proc Natl Acad Sci U S A. 1971 Oct;68(10):2616–2620. doi: 10.1073/pnas.68.10.2616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. PORTER R. R. The hydrolysis of rabbit y-globulin and antibodies with crystalline papain. Biochem J. 1959 Sep;73:119–126. doi: 10.1042/bj0730119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Potter M., Lieberman R. Common individual antigenic determinants in five of eight BALB-c IgA myeloma proteins that bind phosphoryl choline. J Exp Med. 1970 Oct 1;132(4):737–751. doi: 10.1084/jem.132.4.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Potter M., Lieberman R., Dray S. Isoantibodies specific for myeloma gamma-G and gamma-H immunoglobulins of BALB-c mice. J Mol Biol. 1966 Apr;16(2):334–346. doi: 10.1016/s0022-2836(66)80177-8. [DOI] [PubMed] [Google Scholar]
  36. Sher A., Cohn M. Inheritance of an idiotype associated with the immune response of inbred mice to phosphorylcholine. Eur J Immunol. 1972 Aug;2(4):319–326. doi: 10.1002/eji.1830020405. [DOI] [PubMed] [Google Scholar]
  37. WILLIAMS R. C., Jr, KUNKEL H. G. Antibodies to rabbit gamma-globulin after immunizing with various preparations of autologous gamma-globulin. Proc Soc Exp Biol Med. 1963 Mar;112:554–561. doi: 10.3181/00379727-112-28104. [DOI] [PubMed] [Google Scholar]
  38. Westergaard M., von Wettstein D. The synaptinemal complex. Annu Rev Genet. 1972;6:71–110. doi: 10.1146/annurev.ge.06.120172.000443. [DOI] [PubMed] [Google Scholar]
  39. Willims R. C., Jr, Kunkel H. G., Capra J. D. Antigenic specificities related to the cold agglutinin activity of gamma M globulins. Science. 1968 Jul 26;161(3839):379–381. doi: 10.1126/science.161.3839.379. [DOI] [PubMed] [Google Scholar]
  40. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

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