title: Why specific anti-integrase antibodies from HIV-infected patients can efficiently hydrolyze 21-mer oligopeptide corresponding to antigenic determinant of human myelin basic protein.
abstract: Human immunodeficiency virus-infected patients possess anti-integrase (IN) catalytic IgGs and IgMs (abzymes), which, unlike canonical proteases, specifically hydrolyze only intact globular IN. Anti-myelin MBP abzymes from patients with multiple sclerosis and systemic lupus erythematosus efficiently hydrolyze only intact MBP. Anti-MBP and anti-IN abzymes do not hydrolyze several other tested control globular proteins. Here, we show that anti-IN abzymes efficiently hydrolyze a 21-mer oligopeptide (OP21) corresponding to one antigenic determinant (AGD) of MBP, whereas anti-MBP abzymes extremely poorly cleave oligopeptides corresponding to AGDs of IN. All sites of IgG-mediated and IgM-mediated proteolysis of OP21 by anti-IN abzymes were found for the first time by a combination of reverse phase and thin layer chromatography and mass spectrometry. Several clustered sites of OP21 cleavage were revealed and compared with the cleavage sites within the complete IN. Several fragments of OP21 had good homology with many fragments of the IN sequence. The active sites of anti-IN abzymes are known to be located on their light chains, whereas heavy chains are responsible for the affinity for protein substrates. Interactions of intact IN with both light and heavy chains of the abzymes provide high affinity for IN and the specificity of its hydrolysis. Our data suggest that OP21 interacts mainly with the light chains of polyclonal anti-IN abzymes, which possess lower affinity and specificity for substrate. The hydrolysis of the non-cognate OP21 oligopeptide may be also less specific than the hydrolysis of the globular IN because in contrast to previously described serine protease-like abzymes against different proteins, anti-IN abzymes possess serine, thiol, acidic, and metal-dependent protease activities.
authors.affiliation: Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Lavrentiev Ave. 8, Novosibirsk, 630090, Russia.
authors.forename: Elena S
authors.initials: ES
authors.lastname: Odintsova
authors.forename: Pavel S
authors.initials: PS
authors.lastname: Dmitrenok
authors.forename: Anna M
authors.initials: AM
authors.lastname: Timofeeva
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Buneva
authors.forename: Georgy A
authors.initials: GA
authors.lastname: Nevinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000378:metabolism; D017151:Antibodies, Catalytic / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D019427:HIV Integrase / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism*; D059748:Proteolysis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D017151:Antibodies, Catalytic; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009842:Oligopeptides; C048844:anti-IgG; D019427:HIV Integrase
keywords: HIV infected patients; catalytic antibodies; human blood antibodies; hydrolysis of human myelin basic protein peptide