title: Microbial Cryptotopes are Prominent Targets of B-cell Immunity.
abstract: B-cell recognition of microbial antigens may be limited by masking of epitopes within three-dimensional structures (cryptotopes). Here we report that unmasking of cryptotopes by unfolding whole cytomegalovirus (CMV) antigen preparations with the chaotropic reagent Urea and probing with immune sera from healthy individuals (n = 109) increased ELISA signals by 36% in comparison to folded CMV antigens (P < 0.001). ELISA signals increased also significantly upon unfolding of S. aureus or E. coli antigens, whereas unfolded influenza H1N1 or respiratory syncitial virus antigens yielded reduced or unchanged reactivity in comparison to folded ones, respectively. Blocking of CMV cryptotope-specific Abs by incubation of an immunoglobuline preparation and three sera with unfolded CMV antigens enhanced clearly the neutralizing capacity of this immunoglobuline preparation against CMV infection. Thus, B-cell immunity frequently targets cryptotopes on CMV but these Abs are non-neutralizing, may reduce the neutralizing effectiveness of pathogen-specific Abs, and increase during immune maturation following primary CMV infection. The observation of functional consequences of Abs specific for cryptotopes may open whole new avenues to a better understanding of the humoral immune response to CMV and development of more effective vaccines and immunoglobuline preparations.
authors.affiliation: Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Franz J J
authors.initials: FJ
authors.lastname: Rieder
authors.affiliation: Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Biebl
authors.affiliation: Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Marie-Theres
authors.initials: MT
authors.lastname: Kastner
authors.affiliation: Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Blood Donation Center of the Austrian Red Cross for Vienna, Lower Austria and Burgenland, Vienna, Austria.
authors.forename: Christof
authors.initials: C
authors.lastname: Jungbauer
authors.affiliation: Department of Virology, Medical University of Vienna, Kinderspitalgasse 15, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Redlberger-Fritz
authors.affiliation: Department of Pediatrics, Children's Hospital, Birmingham, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Britt
authors.affiliation: Institute for Environmental Hygiene, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Department of Medicine I, Div. of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Steininger
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013211:Staphylococcus aureus / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte