title: Molecular analysis of multicatalytic monoclonal antibodies.
abstract: Recently, our first report demonstrated that Cucumber mosaic virus (CMV)-specific monoclonal antibodies (mAbs) possess DNase-like activity against DNA. In the present study, we show for the first time ever how one mAb (mAb-5) has polyreactive (protease, DNase, and RNase) catalytic activities (catAbs). Amino acid sequence analysis of the encoded variable-genes showed that the light chains of the hybridomas expressed the germline family genes V kappa 1A, bb1.1 and V kappa II, bd2, whose protease and DNase catalytic activities have been reported, while the heavy chain genes were expressed in several germline families (eight of V(H)1/J558, three of V(H)5/V(H)7183, and three of V(H)8/V(H)3609). Interestingly, these germline genes have been well studied in esterolytic antibodies. Here we present for the first time convincing evidence showing that highly purified mAb-5 catalyze both single- and double-stranded DNA and exhibit RNase and protease activity. The greatest therapeutic potential of catAbs could lie in selective prodrug activation. Furthermore, catAbs offer excellent or unique specificity for individual and defined antigenic targets. Therefore, the phenomenon of autoantibody catalysis can potentially be applied to isolate efficient catalytic domains directed against pathogenetically and clinically relevant autoimmune epitopes.
authors.affiliation: Department of Genetics, Faculty of Agriculture, Cairo University, 12613,12 Gamma Street, Giza, 12613, Egypt. haggagsalah@gmail.com
authors.forename: Haggag S
authors.initials: HS
authors.lastname: Zein
authors.forename: Jaime A Teixeira
authors.initials: JA
authors.lastname: da Silva
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Miyatake
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017151:Antibodies, Catalytic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055162:Biocatalysis; D015153:Blotting, Western; D036022:Capsid Proteins / Q000276:immunology*; D017799:Cucumovirus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004277:DNA, Single-Stranded; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides; D004247:DNA; D003851:Deoxyribonucleases; D010447:Peptide Hydrolases