Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 May;80(10):3040–3044. doi: 10.1073/pnas.80.10.3040

Structural bases for public idiotypic specificities of monoclonal antibodies directed against poly(Glu60Ala30Tyr10) and poly(Glu60Ala40) random copolymers.

J Ruf, C Tonnelle, J Rocca-Serra, D Moinier, M Pierres, S T Ju, M E Dorf, J Thèze, M Fougereau
PMCID: PMC393969  PMID: 6190167

Abstract

NH2-terminal amino acid sequences of heavy and light chains of seven poly(Glu60Ala30Tyr10) (GAT) specific hybridoma products derived from DBA/2 and (DBA/2 X BALB/c)F1 hybrid mice and those of BALB/B polyclonal antibodies have been determined over the first 40 residues. Comparison of these sequences with those of nine other GAT or poly(Glu60Ala40) (GA) specific hybridoma products previously reported allowed the following conclusions. (i) Sequences of hybridoma H and L chains are present in the pool of polyclonal antibodies. (ii) The public CGAT (or pGAT) idiotypic specificities are strictly confined to antibodies exhibiting limited heterogeneity with regard to both the variable heavy (VH) and the variable kappa (V kappa) sequences that may be accounted for by one and two germ-line genes, respectively. (iii) The public idiotypic specificities GA-1, expressed by some anti-GAT and most anti-GA antibodies, make use of the same (or similar) VH germ-line genes as the CGAT or pGAT antibodies but possess a distinctive V kappa sequence. (iv) Antibodies expressing neither of the alternative public specificities mentioned above appear to be more heterogeneous and express VH and V kappa sequences that were found to differ from the basic structures defining the CGAT (pGAT) or GA-1 correlates. It is concluded that CGAT (or pGAT) and GA-1 public idiotypic specificities are germ-line markers of both VH and V kappa regions, an observation in agreement with previously reported serological data.

Full text

PDF
3044

Selected References

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

  1. Barstad P., Hubert J., Hunkapiller M., Goetze A., Schilling J., Black B., Eaton B., Richards J., Weigert M., Hood L. Immunoglobulins with hapten-binding activity: structure-function correlations and genetic implications. Eur J Immunol. 1978 Jul;8(7):497–503. doi: 10.1002/eji.1830080709. [DOI] [PubMed] [Google Scholar]
  2. Capra J. D., Nisonoff A. Structural studies on induced antibodies with defined idiotypic specificities. VII. The complete amino acid sequence of the heavy chain variable region of anti-p-azophenylarsenate antibodies from A/J mice bearing a cross-reactive idiotype. J Immunol. 1979 Jul;123(1):279–284. [PubMed] [Google Scholar]
  3. Estess P., Lamoyi E., Nisonoff A., Capra J. D. Structural studies on induced antibodies with defined idiotypic specificities. IX. Framework differences in the heavy- and light-chain-variable regions of monoclonal anti-p-azophenylarsonate antibodies from A/J mice differing with respect to a cross-reactive idiotype. J Exp Med. 1980 Apr 1;151(4):863–875. doi: 10.1084/jem.151.4.863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Francis S. H., Leslie R. G., Hood L., Eisen H. N. Amino-acid sequence of the variable region of the heavy (alpha) chain of a mouse myeloma protein with anti-hapten activity. Proc Natl Acad Sci U S A. 1974 Apr;71(4):1123–1127. doi: 10.1073/pnas.71.4.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ju S. T., Benacerraf B., Dorf M. E. Idiotypic analysis of antibodies to poly(Glu60Ala30Tyr10): interstrain and interspecies idiotypic crossreactions. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6192–6196. doi: 10.1073/pnas.75.12.6192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ju S. T., Dorf M. E., Benacerraf B. Idiotypic analysis of anti-GAT antibodies. III. Determinant specificity and immunoglobulin class distribution of CGAT idiotype. J Immunol. 1979 Mar;122(3):1054–1058. [PubMed] [Google Scholar]
  7. Ju S. T., Dorf M. E. Idiotypic analysis of antibodies against the terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). IV. Induction of CGAT idiotype following immunization with various synthetic polymers containing glutamic acid and tyrosine. Eur J Immunol. 1979 Jul;9(7):553–560. doi: 10.1002/eji.1830090711. [DOI] [PubMed] [Google Scholar]
  8. Ju S. T., Kipps T. J., Theze J., Benacerraf B., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. I. Presence of common idiotypic specificities in both responder and nonresponder mice. J Immunol. 1978 Sep;121(3):1034–1039. [PubMed] [Google Scholar]
  9. Ju S. T., Pierres M., Germain R. N., Benacerraf B., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. VI. Identification and strain distribution of the GA-1 idiotype. J Immunol. 1979 Dec;123(6):2505–2510. [PubMed] [Google Scholar]
  10. Ju S. T., Pierres M., Germain R., Benacerraf B., Dorf M. E. Idiotypic analysis of anti-GAT antibodies. VIII. Comparison of interstrain and allotype-associated idiotypic specificities. J Immunol. 1981 Jan;126(1):177–182. [PubMed] [Google Scholar]
  11. Ju S. T., Pierres M., Waltenbaugh C., Germain R. N., Benacerraf B., Dorf M. E. Idiotypic analysis of monoclonal antibodies to poly(Glu60Ala30Tyr10). Proc Natl Acad Sci U S A. 1979 Jun;76(6):2942–2946. doi: 10.1073/pnas.76.6.2942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  13. Klapper D. G., Wilde C. E., 3rd, Capra J. D. Automated amino acid sequence of small peptides utilizing Polybrene. Anal Biochem. 1978 Mar;85(1):126–131. doi: 10.1016/0003-2697(78)90282-8. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Lazure C., Hum W. T., Gibson D. M. Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus. J Exp Med. 1981 Jul 1;154(1):146–155. doi: 10.1084/jem.154.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leclercq L., Mazié J. C., Sommé G., Thèze J. Monoclonal anti-GAT antibodies with different fine specificities express the same public idiotype. Mol Immunol. 1982 Aug;19(8):1001–1009. doi: 10.1016/0161-5890(82)90308-x. [DOI] [PubMed] [Google Scholar]
  17. Margolies M. N., Marshak-Rothstein A., Gefter M. L. Structural diversity among anti-p-azophenylarsonate monoclonal antibodies from A/J mice; comparison of Id- and Id+ sequences. Mol Immunol. 1981 Dec;18(12):1065–1077. doi: 10.1016/0161-5890(81)90022-5. [DOI] [PubMed] [Google Scholar]
  18. Marshak-Rothstein A., Siekevitz M., Margolies M. N., Mudgett-Hunter M., Gefter M. L. Hybridoma proteins expressing the predominant idiotype of the antiazophenylarsonate response of A/J mice. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1120–1124. doi: 10.1073/pnas.77.2.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nelles M. J., Nisonoff A. Heterogeneity of A/J anti-AR antibodies that express a minor cross-reactive idiotype. J Immunol. 1982 Jun;128(6):2773–2778. [PubMed] [Google Scholar]
  20. Petit C., Joskowicz M., Stanislawski M., Thèze J. Genetic control of the immune response to the terpolymer L-glutamic acid 60-L-alanine 30-L-tyrosine10 (GAT). III. Restricted heterogeneity of the anti-GAT response from BALB/c responder mice. Eur J Immunol. 1979 Dec;9(12):922–928. doi: 10.1002/eji.1830091203. [DOI] [PubMed] [Google Scholar]
  21. Pierres M., Ju S. T., Waltenbaugh C., Dorf M. E., Benacerraf B., Germain R. N. Fine specificity of antibodies to poly(Glu60Ala30Tyr10) produced by hybrid cell lines. Proc Natl Acad Sci U S A. 1979 May;76(5):2425–2429. doi: 10.1073/pnas.76.5.2425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Potter M. Antigen-binding myeloma proteins of mice. Adv Immunol. 1977;25:141–211. [PubMed] [Google Scholar]
  23. Schilling J., Clevinger B., Davie J. M., Hood L. Amino acid sequence of homogeneous antibodies to dextran and DNA rearrangements in heavy chain V-region gene segments. Nature. 1980 Jan 3;283(5742):35–40. doi: 10.1038/283035a0. [DOI] [PubMed] [Google Scholar]
  24. Smithies O., Gibson D., Fanning E. M., Goodfliesh R. M., Gilman J. G., Ballantyne D. L. Quantitative procedures for use with the Edman-Begg sequenator. Partial sequences of two unusual immunoglobulin light chains, Rzf and Sac. Biochemistry. 1971 Dec 21;10(26):4912–4921. doi: 10.1021/bi00802a013. [DOI] [PubMed] [Google Scholar]
  25. Somme G., Leclercq L., Petit C., Thèze J. Genetic control of the immune response to the L-Glu60-L-Ala30-L-Tyr10 (GAT) terpolymer. V. Three types of idiotypic specificities on BALB/c anti-GAT antibodies. Eur J Immunol. 1981 Jun;11(6):493–498. doi: 10.1002/eji.1830110610. [DOI] [PubMed] [Google Scholar]
  26. Sommé G., Serra J. R., Leclercq L., Moreau J. L., Mazie J. C., Moinier D., Fougerèau M., Thèze J. Contribution of the H- and L-chains and of the binding site to the idiotypic specificities of mouse anti-GAT antibodies. Mol Immunol. 1982 Aug;19(8):1011–1019. doi: 10.1016/0161-5890(82)90309-1. [DOI] [PubMed] [Google Scholar]
  27. Theze J., Kapp J. A., Benacerraf B. Immunosuppressive factor(s) extracted from lymphoid cells of nonresponder mice primed with L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) III. Immunochemical properties of the GAT-specific suppressive factor. J Exp Med. 1977 Apr 1;145(4):839–856. doi: 10.1084/jem.145.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Thèze J., Moreau J. L. Genetic control of the immune response to the GAT terpolymer. I. Interstrain and interspecies cross-reactive idiotype. Ann Immunol (Paris) 1978 Jul-Sep;129 100(5):721–726. [PubMed] [Google Scholar]
  29. Thèze J., Sommé G. Genetic control of the immune response to the terpolymer L-glutamic acid(60)-L-alanine(30)-L-tyrosine(10)(GAT). II. Characterization of a cross-reactive idiotype associated with anti-GAT antibodies from responder and nonresponder mice. Eur J Immunol. 1979 Apr;9(4):294–301. doi: 10.1002/eji.1830090409. [DOI] [PubMed] [Google Scholar]
  30. Tonnelle C., Pierres M., Ju S. T., Moinier D., Fougereau M. NH2-terminal amino-acid sequences of poly (Glu60, Ala30, Tyr10) (GAT) and poly (Glu60, Ala40) (GA) monoclonal antibody heavy chains. Mol Immunol. 1981 Nov;18(11):979–984. doi: 10.1016/0161-5890(81)90115-2. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES