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.