title: Highly individual patterns of virus-immune IgG effector responses in humans.
abstract: IgG responses are fundamental to adaptive immunity and document immunological memory of previous pathogen encounter. While specific antigen recognition is mediated by the variable F(ab')2 domain of IgG, various effector functions become activated via the constant Fcγ part bridging IgG-opsonized targets to FcγR-expressing immune effector cells. Traditionally, neutralizing IgG is considered the most appropriate correlate of protective humoral immunity to viruses. However, evidence is increasing that antiviral IgG mediates protection to viruses via activation of FcγRs. Using a test system allowing quantitative detection of virus-immune IgG able to activate FcγRs, sera of healthy individuals and vaccinees were assessed with regard to two prototypical human pathogenic viruses: measles and human cytomegalovirus. Marked differences in the capacity of individuals to generate FcγRI-, FcγRII- and FcγRIII-activating responses were noted. Comparison of FcγR-activating IgG with neutralizing and ELISA IgG concentrations did not correlate for HCMV and only very poorly for MV. Since neither neutralizing IgG nor overall IgG responses faithfully predict the activation of FcγRs, only the simultaneous quantification of IgGs activating defined FcγRs will aid to delineate individual "immunograms" of virus IgG immunity. Such new multiparametric assessment of antiviral IgG qualities could be instrumental in defining correlates of protection and disease progression.
authors.affiliation: Virology, Research Center for Tropical Diseases (CIET), Faculty of Microbiology, University of Costa Rica, PO Box 11501-2060, San José, Costa Rica.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Corrales-Aguilar
authors.affiliation: Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Virchowstrasse 179, 45147, Essen, Germany.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trilling
authors.affiliation: Institute for Virology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Reinhard
authors.affiliation: Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Hermann-Herder-Strasse 11, 79104, Freiburg, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Falcone
authors.affiliation: Institute for Virology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Institute for Virology, Heinrich-Heine-University Düsseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany.
authors.forename: Ortwin
authors.initials: O
authors.lastname: Adams
authors.affiliation: Division Measles, Mumps, Rubella and Viruses Affecting Immunocompromised Patients, Robert Koch Institute, Nordufer 20, 13353, Berlin, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Santibanez
authors.affiliation: Institute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Hermann-Herder-Strasse 11, 79104, Freiburg, Germany. Hartmut.Hengel@uniklinik-freiburg.de.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Hengel
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007223:Infant; D008297:Male; D008459:Measles virus / Q000276:immunology*; D008875:Middle Aged; D017452:Receptors, IgG / Q000378:metabolism*; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG
keywords: Antiviral IgG; ELISA; FcγRs; Human cytomegalovirus; Measles virus; Neutralization