Applied Biochemistry and Biotechnology

, Volume 75, Issue 1, pp 13–24 | Cite as

Mechanism and functional role of antibody catalysis

Original Articles


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.

Index Entries

Catalytic antibodies light chain germline genes somatic maturation VIP asthma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Paul, S., Volle, D.J., Beach, C. M., Johnson, D. R., Powell, M. J., and Massey, R. J. (1989),Science 244, 1158–1162.CrossRefGoogle Scholar
  2. 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. 3.
    Suzuki, H., Imanishi, H., Nakai, T., and Konishi, Y. K. (1992),Biochem. (Life Sci. Adv.) 11, 173–177.Google Scholar
  4. 4.
    Li, L., Kaveri, S., Tyutyulkova, S., Kazatchkine, M., and Paul, S. (1995),J. Immunol. 154, 3328–3332.Google Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 7.
    Kit, Y.-Y, Semenov, D. V., and Nevinsky, G. A. (1996),Biochem. Mol Biol. Intl. 39, 521–527.Google Scholar
  8. 8.
    Kalaga, R., Li, L., O’Dell, J., and Paul, S. (1995),J. Immunol. 155, 2695–2702.Google Scholar
  9. 9.
    Raso, V. and Stollar, B. D. The antibody-enzyme analogy. (1975)Biochemistry 14, 591–599.CrossRefGoogle Scholar
  10. 10.
    Kohen, F., Kim, J. B., Barnard, G., and Linder, H. R. (1979),FEBS Lett. 100, 137–140.CrossRefGoogle Scholar
  11. 11.
    Kohen, F., Kim, J. B., Linder, H. R., Eshhar, Z., and Green, B. (1980),FEBS Lett. 111, 427–431.CrossRefGoogle Scholar
  12. 12.
    Kohen, F., Kim, J.-B., Barnard, G., and Lindner, H. (1980),Biochem. Biophys. Acta 629, 328–337.Google Scholar
  13. 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.Google Scholar
  14. 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.Google Scholar
  15. 15.
    Gramatikova, S. and Christen, P. (1996),J. Biol. Chem. 271, 30,583–30,586.Google Scholar
  16. 16.
    Takagi, M., Kohda, K., Hamuro, T., Harada, A., Yamaguchi, H., Kamachi, M., and Imanaka, T. (1995),FEBS Lett. 375, 273–276.CrossRefGoogle Scholar
  17. 17.
    Izadyar, L., Friboulet, A., Remy, M. H., Roseto, A., and Thomas, D. (1993),Proc. Natl. Acad. Sci. USA. 90, 8876–8880.CrossRefGoogle Scholar
  18. 18.
    Crespeau, H., Laouar, A., and Rochu, D. (1994),C. R. Acad. Sci. Paris de la vie/Life Sci 317, 819–823.Google Scholar
  19. 29.
    Tawfik, D., Chap, R., Green, B., Sela, M., and Eshhar, Z. (1995),Proc. Natl. Acad. Sci. USA 92, 2145–2149.CrossRefGoogle Scholar
  20. 20.
    Sun, M., Mody, B., Eklund, S. H., and Paul, S. (1991),Biol. Chem. 266, 15,571–15,574.Google Scholar
  21. 21.
    Tyutyulkova, S., Gao, Q.-S., Thompson, A., Rennard, A., and Paul, S. (1996),Biochem. Biophys. Acta 1316, 217–223.Google Scholar
  22. 22.
    Matsuura, K., Yamamoto, K., and Sinohara, H. (1994),Biochem. Biophys. Res. Commun. 204, 57–62.CrossRefGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 24.
    Matsuura, K. and Sinohara, H. (1996),Biol. Chem. 377, 587–589.Google Scholar
  25. 25.
    Pollard, S., Meier, W., Chow, P., Rosa, J., and Wiley, D. (1991),Proc. Natl. Acad. Sci. USA 88, 11,320–11,324.Google Scholar
  26. 26.
    Martins, M. A., Shore, S. A., Gerard, N. P., Gerard, C., and Drazen, J. M. (1990),J. Clin. Invest. 85, 170–176.CrossRefGoogle Scholar
  27. 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.Google Scholar
  28. 28.
    Gao, Q.-S., Sun, M., Rees, A., and Paul, S. (1995),J. Mol. Biol. 253, 658–664.CrossRefGoogle Scholar
  29. 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. 30.
    Avrameas, S. (1991),Immunol. Today 12, 154–159.Google Scholar
  31. 31.
    Casali, P. and Notkins, A. L. (1989),Immunol. Today 10, 364–368.CrossRefGoogle Scholar
  32. 32.
    Harindranath, N., Ikematsu, H., Notkins, A. L., and Casali, P. (1993),Int. Immunol. 5, 1523–1533.CrossRefGoogle Scholar
  33. 33.
    Guilbert, B., Dighiero, G., and Avrameas, S. (1982),J. Immunol. 128, 2779–2787.Google Scholar
  34. 34.
    Sun, M., Gao, Q.-S., Kimarskiy, L., Rees, A., and Paul, S. (1997),J. Mol. Biol. 271, 374–385.CrossRefGoogle Scholar
  35. 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.CrossRefGoogle Scholar
  36. 36.
    Paul, S. (1994),Appl. Biochem. Biotechnol. 47, 241–255.Google Scholar
  37. 37.
    Paul, S., Volle, D. J., Powell, M. J., and Massey, R. J. (1990),J. Biol. Chem. 265, 11,910–11,913.Google Scholar
  38. 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.Google Scholar
  39. 39.
    Schwartz, R. S. (1993),Fundamental Immunology, 3rd ed. (Paul, W. E., ed.) Raven, New York pp. 1033–1097.Google Scholar
  40. 40.
    Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S., (1992),Nature 356, 314–317.CrossRefGoogle Scholar
  41. 41.
    Couvineau, A., Rouyer, F. C., Fournier, A., St. Pierre, S., Pipkorn, R., and Laburthe, M. (1984),Biochem. Biophys. Res. Commun. 121, 493–498.CrossRefGoogle Scholar
  42. 42.
    Nelson, M., Brown, R. D., Gibson, J., and Joshua, D. E. (1992),J. Haematol. 81, 223–230.Google Scholar
  43. 43.
    Paul, S. and Ebadi, M. (1993),Neurochem. Int. 23, 197–214.CrossRefGoogle Scholar
  44. 44.
    Paul, S. and Said, S. I. (1987),J. Biol. Chem. 262, 158–162.Google Scholar
  45. 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. 46.
    Ciabattoni, G., Montuschi, P., Curro, D., Togna, G., and Preziosi, P. (1993),Br. J. Pharmacol. 109, 243–250.Google Scholar
  47. 47.
    Sun, L. and Ganea, D. (1993),J. Neuroimmunol. 48, 59–70.CrossRefGoogle Scholar
  48. 48.
    Said, S. I. (1991),Am. Rev. Respir. Dis. 143, S22-S24.Google Scholar
  49. 49.
    Ollerenshaw, S., Jarvis, D., Woolcock, A., Sullivan, C., and Scheibner, T. (1989),N. Eng. J. Med. 320, 1244–1248.CrossRefGoogle Scholar
  50. 50.
    Hakoda, H., Zhouqiu, X., Aizawa, H., Inoue, H., Hirata, M., and Ito, Y. (1991),Am. J. Physiol. 261, L341-L348.Google Scholar
  51. 51.
    Martin, L., Edworthy, S. M., Ryan, J. P., and Fritzler, M. J. (1992),J. Rheum. 19, 1186–1190.Google Scholar
  52. 52.
    Grabar, P. (1983),Immunol. Today 4, 337–340.CrossRefGoogle Scholar
  53. 53.
    Kofier, R. and Wick, G. (1978),Z. Immunitatsforsch Immunobiol. 154, 88–93.Google Scholar
  54. 54.
    Tramontano, A. (1994),Appl. Biochem. Biotechnol. 47, 257–275.Google Scholar
  55. 55.
    Paul, S. (1996),Isr. J. Chem. 36, 207–214.Google Scholar
  56. 56.
    Titmas, R. C. (1994),Appl. Biochem. Biotechnol. 47, 291–292.Google Scholar

Copyright information

© Humana Press Inc 1998

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineUniversity of Texas Medical SchoolHouston

Personalised recommendations