Skip to main content

Advertisement

SpringerLink
Log in

Naturally occurring catalytic antibodies: evidence for preferred development of the catalytic function in IgA class antibodies

  • Research
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

Abstract

IgG class antibodies express catalytic activities rarely and at very low levels. Here, we studied polyclonal IgA and IgG preparations from healthy human sera and saliva for the ability to hydrolyze model peptidyl-aminomethylcoumarin (peptide-AMC) substrates. These substrates permit objective evaluation of the catalytic potential of the antibody classes with minimal effects of noncovalent interactions occurring at sites remote from the reaction center. The IgA preparations hydrolyzed Glu-Ala-Arg-AMC at rates 3-orders of magnitude greater than IgG preparations from the same individuals. The cleavage occurred preferentially on the C terminal side of a basic residue. The activity was confirmed using monoclonal IgAs isolated from patients with multiple myeloma. Active site-directed inhibitors of serine proteases inhibited the catalytic activity and were bound irreversibly by the IgA, suggesting the involvement of a serine protease-like mechanism similar to that utilized by previously described IgM antibodies. These observations suggest that mechanisms underlying B cell clonal selection favor the retention and improvement of catalytic activity in the IgA, but not the IgG compartment of the immune response.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

Ab:

Antibody

AMC:

7-Amino-4-methylcoumarine

CHAPS:

3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonic acid

C domain:

Constant domain

DFP:

Diisopropyl fluorophosphate

FU:

Fluorescence unit

SDS:

Sodium dodecylsulfate

V domain:

Variable domain

References

  1. Chen, T. Y., Huang, C. C., & Tsao, C. J. (1993). Hemostatic molecular markers in nephrotic syndrome. American Journal of Hematology, 44, 276–279.

    Article  PubMed  CAS  Google Scholar 

  2. Dalakas, M. C. (2004). Intravenous immunoglobulin in autoimmune neuromuscular diseases. JAMA, 291, 2367–2375.

    Article  PubMed  CAS  Google Scholar 

  3. Gao, Q. S., Sun, M., Rees, A. R., & Paul, S. (1995). Site-directed mutagenesis of proteolytic antibody light chain. Journal of Molecular Biology, 253, 658–664.

    Article  PubMed  CAS  Google Scholar 

  4. Gololobov, G., Sun, M., & Paul, S. (1999). Innate antibody catalysis. Molecular Immunology, 36, 1215–1222.

    Article  PubMed  CAS  Google Scholar 

  5. Hanson, C. V., Nishiyama, Y., & Paul, S. (2005). Catalytic antibodies and their applications. Current Opinion in Biotechnology, 16, 631–636.

    Article  PubMed  CAS  Google Scholar 

  6. Jolles, S., Sewell, W. A., & Misbah, S. A. (2005). Clinical uses of intravenous immunoglobulin. Clinical and Experimental Immunology, 142, 1–11.

    Article  PubMed  CAS  Google Scholar 

  7. Kalaga, R., Li, L., O’Dell, J. R., & Paul, S. (1995). Unexpected presence of polyreactive catalytic antibodies in IgG from unimmunized donors and decreased levels in rheumatoid arthritis. Journal of Immunology, 155, 2695–2702.

    CAS  Google Scholar 

  8. Kerr, M. A. (1990). The structure and function of human IgA. Biochemical Journal, 271, 285–296.

    PubMed  CAS  Google Scholar 

  9. Krieger, J. W., Crowe, M., & Blank, S. E. (2004). Chronic glutamine supplementation increases nasal but not salivary IgA during 9 days of interval training. Journal of Applied Physiology, 97, 585–591.

    Article  PubMed  CAS  Google Scholar 

  10. Lacroix-Desmazes, S., Bayry, J., Kaveri, S. V., Hayon-Sonsino, D., Thorenoor, N., Charpentier, J., Luyt, C. E., Mira, J. P., Nagaraja, V., Kazatchkine, M. D., Dhainaut, J. F., & Mallet, V. O. (2005). High levels of catalytic antibodies correlate with favorable outcome in sepsis. Proceedings of the National Academy of Sciences of the USA, 102, 4109–4113.

    Article  PubMed  CAS  Google Scholar 

  11. Lacroix-Desmazes, S., Moreau, A., Sooryanarayana, Bonnemain, C., Stieltjes, N., Pashov, A., Sultan, Y., Hoebeke, J., Kazatchkine, M. D., & Kaveri, S. V. (1999). Catalytic activity of antibodies against factor VIII in patients with hemophilia A. Natural Medicine, 5, 1044–1047.

  12. Matsuura, K., Yamamoto, K., & Sinohara, H. (1994). Amidase activity of human Bence Jones proteins. Biochemical and Biophysical Research Communications, 204, 57–62.

    Article  PubMed  CAS  Google Scholar 

  13. Morelock, M. M., Rothlein, R., Bright, S. M., Robinson, M. K., Graham, E. T., Sabo, J. P., Owens, R. R., King, D. J., Norris, S. H., Scher, D. S., Wright, J. L., & Adair, J. R. (1994). Isotype choice for chimeric antibodies affects binding properties. Journal of Biological Chemistry, 269, 13048–13055.

    PubMed  CAS  Google Scholar 

  14. Nevinsky, G. A., & Buneva, V. N. (2003). Catalytic antibodies in healthy humans and patients with autoimmune and viral diseases. Journal of Cellular and Molecular Medicine, 7, 265–276.

    Article  PubMed  CAS  Google Scholar 

  15. Nieva, J., & Wentworth, P. (2004). The antibody-catalyzed water oxidation pathway—a new chemical arm to immune defense? Trends in Biochemical Sciences, 29, 274–278.

    Article  PubMed  CAS  Google Scholar 

  16. Nishiyama, Y., Bhatia, G., Bangale, Y., Planque, S., Mitsuda, Y., Taguchi, H., Karle, S., & Paul, S. (2004). Toward selective covalent inactivation of pathogenic antibodies: A phosphate diester analog of vasoactive intestinal peptide that inactivates catalytic autoantibodies. Journal of Biological Chemistry, 279, 7877–7883.

    Article  PubMed  CAS  Google Scholar 

  17. Nishiyama, Y., Karle, S., Mitsuda, Y., Taguchi, H., Planque, S., Salas, M., Hanson, C., & Paul, S. (2006). Towards irreversible HIV inactivation: Stable gp120 binding by nucleophilic antibodies. Journal of Molecular Recognition, 19, 423–431.

    Article  PubMed  CAS  Google Scholar 

  18. Nishiyama, Y., Taguchi, H., Luo, J. Q., Zhou, Y. X., Burr, G., Karle, S., & Paul, S. (2002). Covalent reactivity of phosphonate monophenyl esters with serine proteinases: An overlooked feature of presumed transition state analogs. Archives of Biochemistry and Biophysics, 402, 281–288.

    Article  PubMed  CAS  Google Scholar 

  19. Odintsova, E. S., Buneva, V. N., & Nevinsky, G. A. (2005). Casein-hydrolyzing activity of sIgA antibodies from human milk. Journal of Molecular Recognition, 18, 413–421.

    Article  PubMed  CAS  Google Scholar 

  20. Paul, S. (1996). Natural catalytic antibodies. Molecular Biotechnology, 5, 197–207.

    PubMed  CAS  Google Scholar 

  21. Paul, S., Karle, S., Planque, S., Taguchi, H., Salas, M., Nishiyama, Y., Handy, B., Hunter, R., Edmundson, A., & Hanson, C. (2004). Naturally occurring proteolytic antibodies: Selective immunoglobulin M-catalyzed hydrolysis of HIV gp120. Journal of Biological Chemistry, 279, 39611–39619.

    Article  PubMed  CAS  Google Scholar 

  22. Paul, S., Li, L., Kalaga, R., Wilkins-Stevens, P., Stevens, F. J., & Solomon, A. (1995). Natural catalytic antibodies: Peptide-hydrolyzing activities of Bence Jones proteins and VL fragment. Journal of Biological Chemistry, 270, 15257–15261.

    Article  PubMed  CAS  Google Scholar 

  23. Paul, S., Nishiyama, Y., Planque, S., & Taguchi, H. (2006). Theory of proteolytic antibody occurrence. Immunology Letters, 103, 8–16.

    Article  PubMed  CAS  Google Scholar 

  24. Paul, S., Planque, S., Zhou, Y. X., Taguchi, H., Bhatia, G., Karle, S., Hanson, C., & Nishiyama, Y. (2003). Specific HIV gp120-cleaving antibodies induced by covalently reactive analog of gp120. Journal of Biological Chemistry, 278, 20429–20435.

    Article  PubMed  CAS  Google Scholar 

  25. Paul, S., Tramontano, A., Gololobov, G., Zhou, Y. X., Taguchi, H., Karle, S., Nishiyama, Y., Planque, S., & George, S. (2001). Phosphonate ester probes for proteolytic antibodies. Journal of Biological Chemistry, 276, 28314–28320.

    Article  PubMed  CAS  Google Scholar 

  26. Paul, S., Volle, D. J., Beach, C. M., Johnson, D. R., Powell, M. J., & Massey, R. J. (1989). Catalytic hydrolysis of vasoactive intestinal peptide by human autoantibody. Science, 244, 1158–1162.

    Article  PubMed  CAS  Google Scholar 

  27. Planque, S., Bangale Y., Song X. T., Karle S., Taguchi H. Poindexter B., Bick R., Edmundson A., Nishiyama Y., & Paul, S. (2004). Ontogeny of proteolytic immunity: IgM serine proteases. Journal of Biological Chemistry, 279, 14024–14032.

    Article  PubMed  CAS  Google Scholar 

  28. Planque, S., Taguchi, H., Burr, G., Bhatia, G., Karle, S., Zhou, Y. X., Nishiyama, Y., & Paul, S. (2003). Broadly distributed chemical reactivity of natural antibodies expressed in coordination with specific antigen binding activity. Journal of Biological Chemistry, 278, 20436–20443.

    Article  PubMed  CAS  Google Scholar 

  29. Polosukhina, D. I., Buneva, V. N., Doronin, B. M., Tyshkevich, O. B., Boiko, A. N., Gusev, E. I., Favorova, O. O., & Nevinsky, G. A. (2005). Hydrolysis of myelin basic protein by IgM and IgA antibodies from the sera of patients with multiple sclerosis. Medical Science Monitor, 11, BR266–BR272.

    PubMed  CAS  Google Scholar 

  30. Ponomarenko, N. A., Durova, O. M., Vorobiev, I. I., Belogurov Jr. A. A., Kurkova, I. N., Petrenko, A. G., Telegin, G. B., Suchkov, S. V., Kiselev, S. L., Lagarkova, M. A., Govorun, V. M., Serebryakova, M. V., Avalle, B., Tornatore, P., Karavanov, A., Morse 3rd H. C., Thomas, D., Friboulet, A., & Gabibov, A. G. (2006). Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen. Proceedings of the National Academy of Sciences of the USA, 103, 281–286.

    Article  PubMed  CAS  Google Scholar 

  31. Powers, J. C., Asgian, J. L., Ekici, O. D., & James, K. E. (2002). Irreversible inhibitors of serine, cysteine, and threonine proteases. Chemical Reviews, 102, 4639–4750.

    Article  PubMed  CAS  Google Scholar 

  32. Ramsland, P. A., Terzyan, S. S., Cloud, G., Bourne, C. R., Farrugia, W., Tribbick, G., Geysen, H. M., Moomaw, C. R., Slaughter, C. A., & Edmundson, A. B. (2006). Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody. Biochemical Journal, 395, 473–481.

    Article  PubMed  CAS  Google Scholar 

  33. Sasso, E. H., Silverman, G. J., & Mannik, M. (1991). Human IgA and IgG F(ab′)2 that bind to staphylococcal protein A belong to the VHIII subgroup. Journal of Immunology, 147, 1877–1883.

    CAS  Google Scholar 

  34. Shuster, A. M., Gololobov, G. V., Kvashuk, O. A., Bogomolova, A. E., Smirnov, I. V., Gabibov, A. G. (1992). DNA hydrolyzing autoantibodies. Science, 256, 665–667.

    Article  PubMed  CAS  Google Scholar 

  35. Sun, M., Gao, Q. S., Kirnarskiy, L., Rees, A., & Paul, S. (1997). Cleavage specificity of a proteolytic antibody light chain and effects of the heavy chain variable domain. Journal of Molecular Biology, 271, 374–385.

    Article  PubMed  CAS  Google Scholar 

  36. Werdan, K. (2001). Intravenous immunoglobulin for prophylaxis and therapy of sepsis. Current Opinion in Critical Care, 7, 354–361.

    Article  PubMed  CAS  Google Scholar 

  37. Zimmerman, M., Ashe, B., Yurewicz, E. G., & Patel, G. (1977). Sensitive assays for trypsin, elastase, and chymotrypsin using new fluorogenic substrates. Analytical Biochemistry, 78, 47–51.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from National Institutes of Health (AI31268, AI058865, AI058684 and AG025304), the Texas Higher Education Coordinating Board and the Hemophilia Association of New York. We thank Robert Dannenbring and Yogesh Bangale for technical assistance.

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas – Houston Medical School, 6431 Fannin, Houston, TX, 77030, USA

    Yukie Mitsuda, Stephanie Planque, Mariko Hara, Hiroaki Taguchi, Yasuhiro Nishiyama & Sudhir Paul

  2. Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Robert Kyle

Authors
  1. Yukie Mitsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stephanie Planque
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariko Hara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Kyle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroaki Taguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuhiro Nishiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. 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

Mitsuda, Y., Planque, S., Hara, M. et al. Naturally occurring catalytic antibodies: evidence for preferred development of the catalytic function in IgA class antibodies. Mol Biotechnol 36, 113–122 (2007). https://doi.org/10.1007/s12033-007-0003-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-007-0003-7

Keywords

Search

Navigation