Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution

Abstract

In proliferating B lymphocytes, somatic mutation of rearranged antibody variable (V)-region genes occurs at high frequency and may have a key role in the selection of these cells1–3. It is of interest in this context to learn in which way single mutations can affect antigen binding and/or idiotypic specificity of an antibody. Previous investigations have analysed spontaneous mutants of myeloma and hybridoma cells in which the mutation affected the antigen-binding specificity of the antibody4–8. Here we describe an antibody mutant that has fully retained antigen-binding specificity but has lost or drastically changed all V-region antigenic determinants (idiotopes) of the wild type as defined by monoclonal anti-idiotope antibodies. The mutant phenotype is generated by a glycine to arginine exchange in the middle of the diversity (D) element, at position 103 of the heavy chain.

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References

  1. 1

    McKean, D. M. et al. Proc. natn. Acad. Sci. U.S.A. 81, 3180–3184 (1984).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Sablitzky, F., Wildner, G. & Rajewsky, K. EMBO J. (in the press).

  3. 3

    Rajewsky, K. & Takemori, T. A. Rev. Immun. 1, 569–607 (1983).

    CAS  Article  Google Scholar 

  4. 4

    Brüggemann, M., Radbruch, A. & Rajewsky, K. EMBO J. l, 629–634 (1982).

    Article  Google Scholar 

  5. 5

    Dildrop, R., Brüggemann, M., Radbruch, A., Rajewsky, K. & Beyreuther, K. EMBO J. l, 635–640 (1982).

    Article  Google Scholar 

  6. 6

    Krawinkel, U., Zoebelein, G., Brüggemann, M., Radbruch, A. & Rajewsky, K. Proc. natn. Acad. Sci. U.S.A. 80, 4997–5001 (1983).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Cook, W. D. & Scharft, M. D. Proc. natn. Acad. Sci. U.S.A. 74, 5687–5691 (1977).

    ADS  CAS  Article  Google Scholar 

  8. 8

    Cook, W. D., Rudikoff, S., Giusti, A. M. & Scharff, M. D. Proc. natn. Acad. Sci. U.S.A. 79, 1240–1244 (1982).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Reth, M., Hämmerling, G. J. & Rajewsky, K. Eur. J. Immun. 8, 393–400 (1978).

    CAS  Article  Google Scholar 

  10. 10

    Neuberger, M. S. & Rajewsky, K. Proc. natn. Acad. Sci. U.S.A. 78, 1138–1143 (1981).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Reth, M., Imanishi-Kari, T. & Rajewsky, K. Eur. J. Immun. 9, 1004–1013 (1979).

    CAS  Article  Google Scholar 

  12. 12

    Rajewsky, K., Takemori, T. & Reth, M. in Monoclonal Antibodies and T Cell Hybridomas— Perspectives and Technical Advances (eds Hämmerling, G. J., Hämmerling, U. & Kearney, J. F.) 399–409 (Eisevier, Amsterdam, 1981).

    Google Scholar 

  13. 13

    Bothwell, A. L. M. et al. Cell 24, 625–637 (1981).

    CAS  Article  Google Scholar 

  14. 14

    Rudikoff, S., Giusti, A., Cook, W. & Scharff, M. D. Proc. natn. Acad. Sci. U.S.A. 79, 1979–1983 (1982).

    ADS  CAS  Article  Google Scholar 

  15. 15

    Clevinger, B., Schilling, J., Hood, L. & Davie, J. M. J. exp. Med. 151, 1059–1070 (1980).

    CAS  Article  Google Scholar 

  16. 16

    Pollock, B. C., Kearney, J. F., Vakil, M. & Perry, R. P. Nature 311, 376–379 (1984).

    ADS  Article  Google Scholar 

  17. 17

    Jeske, D. J., Jarvis, J., Milstein, C. & Capra, D. J. J. Immun. 133, 1090–1092 (1984).

    CAS  PubMed  Google Scholar 

  18. 18

    Berek, C. Eur. J. Immun. 14, 1043–1048 (1984).

    CAS  Article  Google Scholar 

  19. 19

    Sablitzky, F. & Rajewsky, K. EMBO J. 12, 3005–3012 (1984).

    Article  Google Scholar 

  20. 20

    Cumano, A. & Rajewsky, K. Eur. J. Immun. (in the press).

  21. 21

    Padlan, E. A. Q. Rev. Biophys. 10(1), 35–65 (1977).

    CAS  Article  Google Scholar 

  22. 22

    Brüggemann, M. thesis, Univ. Cologne (1984).

  23. 23

    Takemori, T., Tesch, H., Reth, M. & Rajewsky, K. Eur. J. Immun. 12, 1040–1046 (1982).

    CAS  Article  Google Scholar 

  24. 24

    Rajewsky, K., Takemori, T. & Müller, C. E. in Progress in Immunology Vol. 5 (eds Yamamira, Y. & Tada, T.) 533–542 (Academic, New York, 1984).

    Google Scholar 

  25. 25

    Jerne, N. K. Annls Immun. Inst. Past., Paris 125C, 373–389 (1974).

    CAS  Google Scholar 

  26. 26

    Klinman, N. R. et al. Annls Immun. Inst. Past., Paris 127C, 489–504 (1976).

    CAS  Google Scholar 

  27. 27

    Greenwood, F. C. & Hunter, W. M. Biochem. J. 89, 114–117 (1963).

    CAS  Article  Google Scholar 

  28. 28

    Dildrop, R. & Beyreuther, K. Nature 292, 61–63 (1981).

    ADS  CAS  Article  Google Scholar 

  29. 29

    Hewick, R. M., Hunkapiller, M. W., Hood, L. E. & Dreyer, W. J. J. biol. Chem. 256, 7990–7997 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

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Radbruch, A., Zaiss, S., Kappen, C. et al. Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution. Nature 315, 506–508 (1985). https://doi.org/10.1038/315506a0

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