Abstract
IgGs from patients with multiple sclerosis and systemic lupus erythematosus (SLE) purified on MBP-Sepharose in contrast to canonical proteases hydrolyze effectively only myelin basic protein (MBP), but not many other tested proteins. Here we have shown for the first time that anti-MBP SLE IgGs hydrolyze nonspecific tri- and tetrapeptides with an extreme low efficiency and cannot effectively hydrolyze longer 20-mer nonspecific oligopeptides corresponding to antigenic determinants (AGDs) of HIV-1 integrase. At the same time, anti-MBP SLE IgGs efficiently hydrolyze oligopeptides corresponding to AGDs of MBP. All sites of IgG-mediated proteolysis of 21-and 25-mer encephalytogenic oligopeptides corresponding to two known AGDs of MBP were found by a combination of reverse-phase chromatography, TLC, and MALDI spectrometry. Several clustered major, moderate, and minor sites of cleavage were revealed in the case of 21- and 25-mer oligopeptides. The active sites of anti-MBP abzymes are localised on their light chains, while heavy chains are responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of abzymes provide high affinity to MBP and specificity of this protein hydrolysis. The affinity of anti-MBP abzymes for intact MBP is approximately 1000-fold higher than for the oligopeptides. The data suggest that all oligopeptides interact mainly with the light chains of different monoclonal abzymes of total pool of IgGs, which possesses a lower affinity for substrates, and therefore, depending on the oligopeptide sequences, their hydrolysis may be less specific than globular protein and can occur in several sites.
Highlights
It is known, that the occurrence of auto-Abs in increased concentration is a distinctive feature of various autoimmune diseases (ADs)
To exclude possible artefacts due to traces of contaminating proteases, these fractions were separated by SDSPAGE and their proteolytic activity was detected after the extraction of proteins from the excised gel slices as in [9]; only sle-IgGmix and ms-IgGmix preparations were active, when hdIgGmix was catalytically inactive
To [9] it was shown that, in contrast to canonical proteases, the systemic lupus erythematosus (SLE) and Multiple sclerosis (MS) IgGmix purified on myelin basic protein (MBP)-Sepharose hydrolyzed only MBP but not many other tested proteins
Summary
That the occurrence of auto-Abs in increased concentration is a distinctive feature of various autoimmune diseases (ADs) (reviewed in [1,2,3,4,5,6,7,8]). Active artificial antibodies (Abs) or abzymes (Abzs) against transition chemical states of different reactions were studied intensively (reviewed in [1]). Healthy humans and patients with many diseases with insignificant autoimmune reactions usually lack abzymes or develop Abzs with very low catalytic activities, with these activities being often on a borderline of the sensitivity of detection methods (reviewed in [2,3,4,5,6,7,8]). Natural abzymes hydrolyzing DNA, RNA, polysaccharides, oligopeptides (OPs), and proteins are described from the sera of patients with several autoimmune (systemic lupus erythematosus, Hashimoto’s thyroiditis, polyarthritis, multiple sclerosis, asthma, rheumatoid arthritis, etc.) and viral diseases with a pronounced immune system disturbance (viral hepatitis, AIDS, and tick-borne encephalitis) (reviewed in [2,3,4,5,6,7,8,9,10]). Abzymes may play a significant positive and/ or negative role in broadening Ab properties, forming specific pathogenic patterns and clinical settings in different autoimmune conditions [1,2,3,4,5,6,7,8,9,10]
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