Highly individual patterns of virus-immune IgG effector responses in humans

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 Fc gamma part bridging IgG-opsonized targets to Fc gamma R-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 Fc gamma Rs. Using a test system allowing quantitative detection of virus-immune IgG able to activate Fc gamma Rs, 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 Fc gamma RI-, Fc gamma RII- and Fc gamma RIII-activating responses were noted. Comparison of Fc gamma R-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 Fc gamma Rs, only the simultaneous quantification of IgGs activating defined Fc gamma Rs 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.