Hypothesized tolerizing mechanism of IgG. We have discovered conserved T-cell epitopes in IgG that engage natural regulatory T cells. We hypothesize that antibody-derived Treg epitopes (dark blue epitope) activate regulatory T cells, which leads to suppression of effector T cells that recognize effector epitopes (red epitope), like those of IgG hypervariable regions to which central tolerance does not exist. Whether this suppression is mediated by regulatory cytokines alone or by contact-dependent signaling, or both, has yet to be determined.