Feedback regulation of autoimmunity via TCR-centered regulation

The complexity of a self-regulatory system demands a balance between effectors and regulators; that is, it is necessary for both cell types to exist. Regulation of self-reactive T cells can occur at several complementary but different levels: (1) at the level of priming itself: for example, inhibition of expansion of antigen-reactive T cells by regulatory CD4+ CD25+ T cells; (2) after the priming of self-reactive T cells, regulatory T-cell populations with reactivity to distinct self-determinants derived from the T-cell receptor (TCR) can be engaged via a negative feedback mechanism. Thus, these mechanisms ensure induction of effective and appropriately limited responses against foreign antigens while preventing autoreactivity from inflicting self-damage.