Antibodies to HIV integrase catalyze site-specific degradation of their antigen

Odintsova, Elena S.; Баранова, Светлана Владимировна; Dmitrenok, Pavel S.; Rasskazov, V. A.; Calmels, Christina; Parissi, Vincent; Andréola, Marie‐Line; Buneva, Valentina N.; Zakharova, Olga D.; Nevinsky, Georgy A.

doi:10.1093/intimm/dxr065

Cited by 24 publications

(72 citation statements)

References 34 publications

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“…The relative rate of the MCA formation was approximately 4-5- (sh-OP2) and 20-25-fold (sh-OX3) higher in the presence of ms-IgG mix than that for sle-IgG mix . Similar situation was observed for longer nonspecific 20-mer oligopeptides in-OP1 and in-OP2 (Fig 1B) corresponding to viral integrase, that, as revealed by a MALDI analysis, contain several sites of IN cleavage in the case of anti-IN IgGs from HIV-infected patients [33], [34]. Nonspecific in-OP1 and in-OP2 oligopeptides corresponding to HIV integrase were slightly hydrolyzed nonspecifically after 24 of the incubation, but there was no detectable difference in the fluorescence intensities of the spots after the incubation of these OPs without (lanes 2) and with sle-IgG mix (lanes 3) (Fig.…”

Section: Resultssupporting

confidence: 80%

“…At the same time, we have seen that long incubation of MBP with MS and SLE IgGs (48–72 h), especially with abzymes possessing high proteolytic activity, led to the formation of short and very short fragments. Similar situation was observed for anti-IN abzymes from HIV-infected patients in the hydrolysis of viral integrase [33], [34]. It means that the total pools of various IgGs can contain different subfractions of anti-protein abzymes, which are capable to hydrolyze a target protein in many sites but with different rates.…”

Section: Discussionsupporting

confidence: 64%

“…Polyclonal IgG preparations from patients with rheumatoid arthritis also displayed Pro-Phe-Arg-MCA-hydrolyzing activity [32]. Anti-integrase IgGs and IgMs from HIV-infected patients hydrolyze not only globular HIV-1 integrase but also different specific and nonspecific tri- and tetraoligopeptides [33], [34]. Therefore, first we have analyzed the efficiency of hydrolysis of nonspecific tri- and tetrapeptides using sle-IgG mix and ms-IgG mix purified by affinity chromatography on MBP-Sepharose.…”

Section: Resultsmentioning

confidence: 99%

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Multiple Sites of the Cleavage of 21- and 25-Mer Encephalytogenic Oligopeptides Corresponding to Human Myelin Basic Protein (MBP) by Specific Anti-MBP Antibodies from Patients with Systemic Lupus Erythematosus

et al. 2013

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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.

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Section: Resultssupporting

confidence: 80%

Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Multiple Sites of the Cleavage of 21- and 25-Mer Encephalytogenic Oligopeptides Corresponding to Human Myelin Basic Protein (MBP) by Specific Anti-MBP Antibodies from Patients with Systemic Lupus Erythematosus

et al. 2013

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“…Polyclonal IgG preparations from patients with rheumatoid arthritis also displayed Pro-PheArg-MCA-hydrolyzing activity [32]. Anti-integrase IgGs and IgMs from HIV-infected patients hydrolyze not only globular HIV-1 integrase but also different specific and nonspecific tri-and tetraoligopeptides [33,34]. Therefore, first we have analyzed the efficiency of hydrolysis of nonspecific tri-and tetrapeptides using sle-IgG mix and ms-IgG mix purified by affinity chromatography on MBP-Sepharose.…”

Section: Ab-dependent Hydrolysis Of Oligopeptidesmentioning

confidence: 99%

“…All sites corresponding to major and moderate products of the cleavage are shown by long and short arrows respectively, while to minor ones by diamonds (panels C and F). doi:10.1371/journal.pone.0051600.g006 KIIGQVRDQAE (in-OP2) [33,34]. All mentioned OPs contained fluorescent residue 6-O-(Carboxymethyl)fluorescein ethyl ester (X) on its N-terminus.…”

Section: Ab Proteolytic Activity Assaymentioning

confidence: 99%

Multiple sites of the cleavage of 17- and 19-mer encephalytogenic oligopeptides corresponding to human myelin basic protein (MBP) by specific anti-MBP antibodies from patients with systemic lupus erythematosus

et al. 2012

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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.

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Autoantibodies in HIV‐infected patients: Cross site‐specific hydrolysis of H1 histone and myelin basic protein

et al. 2018

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Histones act as damage‐associated molecules, while anti‐DNA antibodies are directed against histone‐DNA nucleosomal complexes. Myelin basic protein (MBP) plays an important role in the pathogenesis of multiple sclerosis. Autoantibodies (Abs) with enzymatic activities are the distinctive feature of some autoimmune and viral diseases. Abzymes with proteolytic activity against different proteins specifically hydrolyze only these specific proteins. Using chromatography of IgGs on columns with immobilized H1 histone and then by chromatography of the fraction having an affinity for the histone (eluted upon loading) on MBP Sepharose, the anti‐MBP antibodies were obtained. Anti‐H1 antibodies were obtained using these columns in reverse order. IgGs against H1 and MBP effectively hydrolyze both H1 histone and MBP but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H1 histone and MBP by abzymes against these proteins are found. The hydrolysis of MBP by anti‐MBP IgGs occurs at four clusters (22 sites of the hydrolysis) locating at four known antigenic determinants of MBP. Anti‐H1 Abs hydrolyze MBP only at one cluster (11 sites of the hydrolysis); this cluster is only partially overlapped with one of the four MBP clusters. Anti‐H1 antibodies hydrolyze H1 at five sites of one cluster of the protein when anti‐MBP IgGs cleavage this histone at two clusters containing 17 sites of the cleavage. Anti‐H1 and anti‐MBP abzymes are the first examples of Abs possessing not only with cross‐complexing but also with catalytic cross‐reactivity. The existence of cross‐reactivity of abzymes against histones and MBP represent great danger to humans. © 2018 BioFactors, 45(2):211–222, 2019

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Antibodies to HIV integrase catalyze site-specific degradation of their antigen

Cited by 24 publications

References 34 publications

Multiple Sites of the Cleavage of 21- and 25-Mer Encephalytogenic Oligopeptides Corresponding to Human Myelin Basic Protein (MBP) by Specific Anti-MBP Antibodies from Patients with Systemic Lupus Erythematosus

Multiple Sites of the Cleavage of 21- and 25-Mer Encephalytogenic Oligopeptides Corresponding to Human Myelin Basic Protein (MBP) by Specific Anti-MBP Antibodies from Patients with Systemic Lupus Erythematosus

Multiple sites of the cleavage of 17- and 19-mer encephalytogenic oligopeptides corresponding to human myelin basic protein (MBP) by specific anti-MBP antibodies from patients with systemic lupus erythematosus

Autoantibodies in HIV‐infected patients: Cross site‐specific hydrolysis of H1 histone and myelin basic protein

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