How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP

Belov, Sergey; Buneva, Valentina N.; Nevinsky, Georgy A.

doi:10.1002/jmr.2637

Cited by 8 publications

(11 citation statements)

References 56 publications

(213 reference statements)

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“…Cross‐complexation of antibodies against different proteins with other proteins is a known phenomenon . At the same time, cross‐catalysis in the case of canonical enzymes is a very rare phenomenon.…”

Section: Resultsmentioning

confidence: 99%

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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Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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“…Hydrolysis of H2a and H2b by Abs against these histones [33,35] as well as MBP with abzymes against MBP [6][7][8]19,22,32,53] was shown earlier. It was previously shown that pools of anti-MBP Abs contain abzymes of four different types, resembling serine-, thiol-, acidic-like, and metal-dependent proteases, the ratio of which is individual for every autoimmune pathology [4][5][6][7][8][13][14][15]19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Catalysis of the transformation of substrates can occur only after the formation of their complexes with abzymes and enzymes. Interestingly, non-specific cross-complexation has also been described for a large number of very different enzymes [49][50][51][52][53]. However, canonic enzymes usually catalyze only one chemical reaction and catalytic conversion by enzymes of unspecific ligands after complexes formation (catalytic cross-reactivity) is an extremely rare case [49][50][51][52][53].…”

Section: Elisa Of Anti-mbp and Anti-histones Autoantibodiesmentioning

confidence: 99%

“…Interestingly, non-specific cross-complexation has also been described for a large number of very different enzymes [49][50][51][52][53]. However, canonic enzymes usually catalyze only one chemical reaction and catalytic conversion by enzymes of unspecific ligands after complexes formation (catalytic cross-reactivity) is an extremely rare case [49][50][51][52][53]. All described data for abzymes against various proteins also hydrolyze only their specific globular proteins [3][4][5][6][7][8][9][10][11][12][13][14][15][19][20][21][22][32][33][34][35][36][37][38][39][40][41].…”

Section: Elisa Of Anti-mbp and Anti-histones Autoantibodiesmentioning

confidence: 99%

“…It was previously shown that even IgG preparations against all five histones (H1-H4), as well as against MBP, hydrolyze only histones and MBP, but not some other control proteins: HIV-1 integrase, HIV-1 reverse transcriptase, bovine serum albumin, human lactoferrin, ferritin, hen egg lysozyme, bovine aldolase, and human milk casein [19][20][21]32,35,39,40,53]. Electrophoretically homogeneous antibodies against H2a, H2b, and MBP obtained in this work (Figure 1) efficiently hydrolyze H2a, H2b, and MBP (Figure 2A,B) but did not hydrolyze six native globular control proteins and denatured lysozyme (Figure 2C).…”

Section: Sds-page Analysis Of Catalytic Cross-reactivitymentioning

confidence: 99%

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HIV-Infected Patients: Cross Site-Specific Hydrolysis of H2a and H2b Histones and Myelin Basic Protein with Antibodies against These Three Proteins

et al. 2020

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Anti-DNA antibodies are usually produced against histone-DNA complexes appearing during cell apoptosis, while histones are known as damage-associated molecules. A myelin sheath of axons contains myelin basic protein (MBP) playing an important role in the pathogenesis of autoimmune diseases. Antibodies with enzymatic activities (abzymes) are distinctive features of some autoimmune and viral diseases. Abzymes against different proteins can usually only hydrolyze these specific proteins. Using sequential chromatographies of homogeneous IgG preparations from sera of HIV-infected patients on columns with immobilized MBP, H2a, and H2b histones, the anti-MBP, anti-H2a, and anti-H2b antibodies were obtained. It was first shown that IgGs against H2a and H2b effectively hydrolyze these histones and MBP, while anti-MBP split MBP, H2a, and H2b, but no other control proteins. Using the MALDI mass spectrometry, the cleavage sites of H2a, H2b, and MBP by abzymes against these three proteins were found. Among 14 sites of hydrolysis of H2a by IgGs against H2a and 10 sites by anti-MBP IgGs, only one site of hydrolysis was the same for these abzymes. Eleven cleavage sites of H2b with IgGs against H2b and 10 sites of its hydrolysis with antibodies against MBP were different. Anti-H2a, anti-H2b, and anti-MBP abzymes are unpredictable examples of IgGs possessing not only cross-complexation but also catalytic cross-reactivity, which may be a common phenomenon for such abzymes in patients with different autoimmune diseases. The existence of cross-reactivity of abzymes against H2a and H2b histones and MBP represent a great danger to humans since, in contrast with MBP, histones due to cell apoptosis constantly occur in human blood. Anti-H2a, anti-H2b, and anti-MBP can attack and hydrolyze myelin basic protein of the myelin sheath of axons and plays a negative role in the pathogenesis of several pathologies.

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Epothilone D Modulates Autism-like Behaviors in the BTBR Mouse Model of Autism Spectrum Disorder

et al. 2022

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How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP

Cited by 8 publications

References 56 publications

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

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

HIV-Infected Patients: Cross Site-Specific Hydrolysis of H2a and H2b Histones and Myelin Basic Protein with Antibodies against These Three Proteins

Epothilone D Modulates Autism-like Behaviors in the BTBR Mouse Model of Autism Spectrum Disorder

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