Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.

Autor:	Brown EL; Center for Infectious Diseases, University of Texas School of Public Health, Houston, Texas 77030,; Department of Extracellular Matrix Biology, The Texas A&M University Institute of Biosciences and Technology, Houston, Texas 77030, and. Electronic address: Eric.L.Brown@uth.tmc.edu., Nishiyama Y; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Dunkle JW; Center for Infectious Diseases, University of Texas School of Public Health, Houston, Texas 77030., Aggarwal S; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Planque S; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Watanabe K; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Csencsits-Smith K; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Bowden MG; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030., Kaplan SL; Department of Pediatrics, Baylor College of Medicine and the Texas Children's Hospital, Houston, Texas 77030., Paul S; Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas-Houston Medical School, Houston, Texas 77030,. Electronic address: Sudhir.Paul@uth.tmc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2012 Mar 23; Vol. 287 (13), pp. 9940-9951. Date of Electronic Publication: 2012 Feb 02.
DOI:	10.1074/jbc.M111.330043
Abstrakt:	Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b-binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed.
Databáze:	MEDLINE
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