REVIEW: Antibody Proteases: Induction of Catalytic Response

A. G. Gabibov^1,2*, A. Friboulet³, D. Thomas³, A. V. Demin⁴, N. A. Ponomarenko¹, I. I. Vorobiev¹, D. Pillet³, M. Paon³, E. S. Alexandrova¹, G. B. Telegin⁵, A. V. Reshetnyak², O. V. Grigorieva², N. V. Gnuchev⁴, K. A. Malishkin⁶, and D. D. Genkin⁶

¹Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117198 Russia; fax: (095) 310-7007; E-mail: gabibov@ibch.ru

²School of Chemistry, Lomonosov Moscow State University, Moscow, 119899 Russia

³Compiegne Technological University, Compiegne, France

⁴Institute of Gene Biology, Russian Academy of Sciences, ul. Vavilova 34/5, Moscow, 117984 Russia

⁵Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia; fax: (27) 790-527

⁶ASGL-Scientific Laboratories, Charity, P.O. Box 32, St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received May 27, 2002; Revision received July 12, 2002

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Most of the data accumulated throughout the years on investigation of catalytic antibodies indicate that their production increases on the background of autoimmune abnormalities. The different approaches to induction of catalytic response toward recombinant gp120 HIV-1 surface protein in mice with various autoimmune pathologies are described. The peptidylphosphonate conjugate containing structural part of gp120 molecule is used for reactive immunization of NZB/NZW F₁, MRL, and SJL mice. The specific modification of heavy and light chains of mouse autoantibodies with Val-Ala-Glu-Glu-Glu-Val-PO(OPh)₂ reactive peptide was demonstrated. Increased proteolytic activity of polyclonal antibodies in SJL mice encouraged us to investigate the production of antigen-specific catalytic antibodies on the background of induced experimental autoimmune encephalomyelitis (EAE). The immunization of autoimmune-prone mice with the engineered fusions containing the fragments of gp120 and encephalitogenic epitope of myelin basic protein (MBP_89-104) was made. The proteolytic activity of polyclonal antibodies isolated from the sera of autoimmune mice immunized by the described antigen was shown. Specific immune response of SJL mice to these antigens was characterized. Polyclonal antibodies purified from sera of the immunized animals revealed proteolytic activity. The antiidiotypic approach to raise the specific proteolytic antibody as an “internal image” of protease is described. The “second order” monoclonal antibodies toward subtilisin Carlsberg revealed pronounced proteolytic activity.

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KEY WORDS: proteolysis, catalytic antibodies, abzymes, antiidiotypic antibodies, reactive immunization, peptidylphosphonates, HIV-1, gp120, autoimmune inbred lines MRL, NZB/NZW F₁, and SJL

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