Development of a recombinant immunotoxin for the immunotherapy of autoreactive lymphocytes expressing MOG-specific BCRs.

Objective: Myelin oligodendrocyte glycoprotein (MOG) is one of the major autoantigens in multiple sclerosis (MS), therefore selective depletion of autoreactive lymphocytes exposing MOG-specific B cell receptors (BCRs) would be beneficial in terms of MS treatment.

Results: Using E. coli we generated an efficient protocol for the purification of the recombinant immunotoxin DT-MOG composed of the extracellular Ig-like domain of MOG fused in frame with the catalytic and translocation subunits of diphtheria toxin (DT, Corynebacterium diphtheriae) under native conditions with a final yield of 1.

Antibody-antigen pair probed by combinatorial approach and rational design: bringing together structural insights, directed evolution, and novel functionality.

The unique hypervariability of the immunoglobulin (Ig) superfamily provides a means to create both binding and catalytic antibodies with almost any desired specificity and activity. The diversity of antigens and concept of adaptive response suggest that it is possible to find an antigen pair to any raised Ig. In the current review we discuss combinatorial approaches, which makes it possible to obtain an antibody with predefined properties, followed by 3D structure-based rational design to enhance or dramatically change its characteristics.

RNA-hydrolyzing activity of human serum albumin and its recombinant analogue.

The comparative analysis of RNA-hydrolyzing activity of albumin from human serum and albumin expressed in methylotrophic yeast Pichia pastoris has been carried out. The rate of polyribonucleotide phosphodiester bond cleavage in the presence of recombinant albumin has been found to be similar to that of the reaction mediated by the native protein. According to 31P NMR data, RNA hydrolysis follows the mechanism of intermolecular trans-esterification to yield 2',3'-cyclophosphodiester reaction products that are further slowly hydrolyzed to form nucleoside-3'- and nucleoside-2'-phosphates.

Catalytic autoantibodies in clinical autoimmunity and modern medicine.

Abzymes (catalytic autoantibodies) belong to an absolutely new group of physiologically active substances with dual characteristics: they represent a pool of canonical autoantibodies and possess catalytic activity. Among them, proteolytic and DNA-hydrolyzing autoantibodies are of special value. Abzymes are an important pathogenic factor in the progression of clinical autoimmunity syndrome.

Catalytic antibodies in clinical and experimental pathology: human and mouse models.

Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes.