Skip to main content
SpringerLink
Log in

Mechanism and functional role of antibody catalysis

  • Original Articles
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The light (L) chain of a model antibody (Ab) was deduced to contain a serine protease-like catalytic site capable of cleaving peptide bonds. The catalytic site is encoded by a germline VL gene. The catalytic activity can potentially be improved by somatic sequence diversification and pairing of the L chain with the appropriate heavy chain. Autoimmune disease is associated with increased synthesis of antigen (Ag)-specific Abs, but the reasons for this phenomenon are not known. Only recently has attention turned to the functional role of the catalytic function. Preliminary studies confirm that the catalytic cleavage of peptide bonds is a more potent means to achieve Ag neutralization, compared to reversible Ag binding. Administration of a monoclonal Ab to VIP in experimental animals induces an inflammatory response in the airways, suggesting that catalytic autoantibodies to this peptide found in airway disease and lupus are capable of causing airway dysfunction. The phenomenon of autoantibody catalysis can potentially be applied to isolate efficient catalysts directed against tumor or microbial Ags by exposing the autoimmune repertoire to such Ags or their analogs capable of recruiting the germline VL gene encoding the catalytic site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Paul, S., Volle, D.J., Beach, C. M., Johnson, D. R., Powell, M. J., and Massey, R. J. (1989),Science 244, 1158–1162.

    Article  CAS  Google Scholar 

  2. Paul, S., Sun, M., Mody, R., Eklund, S. H., Beach, C. M., Massey, R. J., and Hamel, F. (1991),J. Biol. Chem. 256, 16,128–16,134.

    Google Scholar 

  3. Suzuki, H., Imanishi, H., Nakai, T., and Konishi, Y. K. (1992),Biochem. (Life Sci. Adv.) 11, 173–177.

    CAS  Google Scholar 

  4. Li, L., Kaveri, S., Tyutyulkova, S., Kazatchkine, M., and Paul, S. (1995),J. Immunol. 154, 3328–3332.

    CAS  Google Scholar 

  5. Shuster, A. M., Gololobov, G. V., Kvashuk, O. A., Bogomolova, A. E., Smirnov, I. V., and Gabibov, A. G. (1992),Science 256, 665–667.

    Article  CAS  Google Scholar 

  6. Gololobov, G. V., Chernova, E. A., Schourov, D. V., Smirnov, I. V., Kudelina, I. A., and Gabibov, A. G. (1995),Proc. Natl. Acad. Sci. USA 92, 254–257.

    Article  CAS  Google Scholar 

  7. Kit, Y.-Y, Semenov, D. V., and Nevinsky, G. A. (1996),Biochem. Mol Biol. Intl. 39, 521–527.

    CAS  Google Scholar 

  8. Kalaga, R., Li, L., O’Dell, J., and Paul, S. (1995),J. Immunol. 155, 2695–2702.

    CAS  Google Scholar 

  9. Raso, V. and Stollar, B. D. The antibody-enzyme analogy. (1975)Biochemistry 14, 591–599.

    Article  CAS  Google Scholar 

  10. Kohen, F., Kim, J. B., Barnard, G., and Linder, H. R. (1979),FEBS Lett. 100, 137–140.

    Article  CAS  Google Scholar 

  11. Kohen, F., Kim, J. B., Linder, H. R., Eshhar, Z., and Green, B. (1980),FEBS Lett. 111, 427–431.

    Article  CAS  Google Scholar 

  12. Kohen, F., Kim, J.-B., Barnard, G., and Lindner, H. (1980),Biochem. Biophys. Acta 629, 328–337.

    CAS  Google Scholar 

  13. Paul S., Sun, M., Mody, R., Tewary, H. K., Mehrotra, S., Gianferrara, T., Meldal, M., and Tramontano, A. (1992),J. Biol. Chem. 267, 13,142–13,145.

    CAS  Google Scholar 

  14. Savitsky, A. P., Nelen, M. I., Yatsmirsky, A. K., Demcheva, M. V., Ponomarev, G. V., and Sinikov, I. V. (1994),Appl. Biochem. Biotechnol. 47, 317–327.

    CAS  Google Scholar 

  15. Gramatikova, S. and Christen, P. (1996),J. Biol. Chem. 271, 30,583–30,586.

    CAS  Google Scholar 

  16. Takagi, M., Kohda, K., Hamuro, T., Harada, A., Yamaguchi, H., Kamachi, M., and Imanaka, T. (1995),FEBS Lett. 375, 273–276.

    Article  CAS  Google Scholar 

  17. Izadyar, L., Friboulet, A., Remy, M. H., Roseto, A., and Thomas, D. (1993),Proc. Natl. Acad. Sci. USA. 90, 8876–8880.

    Article  CAS  Google Scholar 

  18. Crespeau, H., Laouar, A., and Rochu, D. (1994),C. R. Acad. Sci. Paris de la vie/Life Sci 317, 819–823.

    CAS  Google Scholar 

  19. Tawfik, D., Chap, R., Green, B., Sela, M., and Eshhar, Z. (1995),Proc. Natl. Acad. Sci. USA 92, 2145–2149.

    Article  CAS  Google Scholar 

  20. Sun, M., Mody, B., Eklund, S. H., and Paul, S. (1991),Biol. Chem. 266, 15,571–15,574.

    Google Scholar 

  21. Tyutyulkova, S., Gao, Q.-S., Thompson, A., Rennard, A., and Paul, S. (1996),Biochem. Biophys. Acta 1316, 217–223.

    Google Scholar 

  22. Matsuura, K., Yamamoto, K., and Sinohara, H. (1994),Biochem. Biophys. Res. Commun. 204, 57–62.

    Article  CAS  Google Scholar 

  23. Paul, S., Li, L., Kalaga, R., Wilkins-Stevens, P., Stevens, F. J., and Solomon, A. (1995),J. Biol. Chem. 270, 15,257–15,261.

    Article  CAS  Google Scholar 

  24. Matsuura, K. and Sinohara, H. (1996),Biol. Chem. 377, 587–589.

    CAS  Google Scholar 

  25. Pollard, S., Meier, W., Chow, P., Rosa, J., and Wiley, D. (1991),Proc. Natl. Acad. Sci. USA 88, 11,320–11,324.

    CAS  Google Scholar 

  26. Martins, M. A., Shore, S. A., Gerard, N. P., Gerard, C., and Drazen, J. M. (1990),J. Clin. Invest. 85, 170–176.

    Article  CAS  Google Scholar 

  27. Gao, Q.-S., Sun, M., Tyutyulkova, S., Webster, D., Rees, A., Tramontano, A., Massey, R., and Paul, S. (1994),J. Biol. Chem. 269, 32,389–32,393.

    CAS  Google Scholar 

  28. Gao, Q.-S., Sun, M., Rees, A., and Paul, S. (1995),J. Mol. Biol. 253, 658–664.

    Article  CAS  Google Scholar 

  29. Schowen, R. L. (1978), inTransition States of Biochemical Processes (Gandour, R. D. and Schowen, R. L., eds.), Plenum, New York, Chapter 2.

    Google Scholar 

  30. Avrameas, S. (1991),Immunol. Today 12, 154–159.

    CAS  Google Scholar 

  31. Casali, P. and Notkins, A. L. (1989),Immunol. Today 10, 364–368.

    Article  CAS  Google Scholar 

  32. Harindranath, N., Ikematsu, H., Notkins, A. L., and Casali, P. (1993),Int. Immunol. 5, 1523–1533.

    Article  CAS  Google Scholar 

  33. Guilbert, B., Dighiero, G., and Avrameas, S. (1982),J. Immunol. 128, 2779–2787.

    CAS  Google Scholar 

  34. Sun, M., Gao, Q.-S., Kimarskiy, L., Rees, A., and Paul, S. (1997),J. Mol. Biol. 271, 374–385.

    Article  CAS  Google Scholar 

  35. Paul, S., Said, S. I., Thompson, A. B., Volle, D. J., Agrawal, D. K., Foda, H., and de la Rocha, S. (1989),J. Neuroimmunol. 23, 133–142.

    Article  CAS  Google Scholar 

  36. Paul, S. (1994),Appl. Biochem. Biotechnol. 47, 241–255.

    CAS  Google Scholar 

  37. Paul, S., Volle, D. J., Powell, M. J., and Massey, R. J. (1990),J. Biol. Chem. 265, 11,910–11,913.

    CAS  Google Scholar 

  38. Paul, S., Li, L., Kalaga, R., O’Dell, R. E., Dannenbring, Jr., R. E., Swindells, S., Hinrichs, S., Caturegli, P., and Rose, N. (1997),J. Immunol. 159, 1530–1536.

    CAS  Google Scholar 

  39. Schwartz, R. S. (1993),Fundamental Immunology, 3rd ed. (Paul, W. E., ed.) Raven, New York pp. 1033–1097.

    Google Scholar 

  40. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S., (1992),Nature 356, 314–317.

    Article  CAS  Google Scholar 

  41. Couvineau, A., Rouyer, F. C., Fournier, A., St. Pierre, S., Pipkorn, R., and Laburthe, M. (1984),Biochem. Biophys. Res. Commun. 121, 493–498.

    Article  CAS  Google Scholar 

  42. Nelson, M., Brown, R. D., Gibson, J., and Joshua, D. E. (1992),J. Haematol. 81, 223–230.

    CAS  Google Scholar 

  43. Paul, S. and Ebadi, M. (1993),Neurochem. Int. 23, 197–214.

    Article  CAS  Google Scholar 

  44. Paul, S. and Said, S. I. (1987),J. Biol. Chem. 262, 158–162.

    CAS  Google Scholar 

  45. Paul, S. (1998), inPro-inflammatory and Anti-inflammatory Peptides, Lung Biology in Health and Disease, Said, S. I., ed.) Marcel Dekker, New York, Chapter 19, pp 441–457.

    Google Scholar 

  46. Ciabattoni, G., Montuschi, P., Curro, D., Togna, G., and Preziosi, P. (1993),Br. J. Pharmacol. 109, 243–250.

    CAS  Google Scholar 

  47. Sun, L. and Ganea, D. (1993),J. Neuroimmunol. 48, 59–70.

    Article  CAS  Google Scholar 

  48. Said, S. I. (1991),Am. Rev. Respir. Dis. 143, S22-S24.

    CAS  Google Scholar 

  49. Ollerenshaw, S., Jarvis, D., Woolcock, A., Sullivan, C., and Scheibner, T. (1989),N. Eng. J. Med. 320, 1244–1248.

    Article  CAS  Google Scholar 

  50. Hakoda, H., Zhouqiu, X., Aizawa, H., Inoue, H., Hirata, M., and Ito, Y. (1991),Am. J. Physiol. 261, L341-L348.

    CAS  Google Scholar 

  51. Martin, L., Edworthy, S. M., Ryan, J. P., and Fritzler, M. J. (1992),J. Rheum. 19, 1186–1190.

    CAS  Google Scholar 

  52. Grabar, P. (1983),Immunol. Today 4, 337–340.

    Article  CAS  Google Scholar 

  53. Kofier, R. and Wick, G. (1978),Z. Immunitatsforsch Immunobiol. 154, 88–93.

    Google Scholar 

  54. Tramontano, A. (1994),Appl. Biochem. Biotechnol. 47, 257–275.

    CAS  Google Scholar 

  55. Paul, S. (1996),Isr. J. Chem. 36, 207–214.

    CAS  Google Scholar 

  56. Titmas, R. C. (1994),Appl. Biochem. Biotechnol. 47, 291–292.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Texas Medical School, 77030, Houston, TX

    Sudhir Paul

Authors
  1. Sudhir Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sudhir Paul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paul, S. Mechanism and functional role of antibody catalysis. Appl Biochem Biotechnol 75, 13–24 (1998). https://doi.org/10.1007/BF02787705

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02787705

Index Entries

Search

Navigation