Hypothesized tolerizing mechanism of IgG. Conserved T-cell epitopes in IgG that engage nTregs have been discovered. The authors hypothesize that antibody-derived Treg epitopes (dark blue epitope) activate Tregs, leading 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 whether contact-dependent signaling also plays a role, has yet to be determined. See the complete figure in the article beginning on page 3303.