In addition to its role in protection against pathogens, a second critical role of the MHC and Ir genes is to safeguard against self-reactivity by restriction of the immune response to self. In this regard, the immune system has developmental checkpoints for the maturation of a T cell. As a naïve T cell expressing a pre-TCR migrates from the bone marrow to the thymus, rearrangement of α and β TCR genes occurs and T cells that have either too high avidity or lack of recognition of self-antigens are selected against and subsequently programmed for cell death. This selection mechanism for generating mature αβ TCRs is named central tolerance. Further, peripheral mechanisms of tolerance are able to suppress autoreactive T cells through certain subsets of cells including regulatory T cells (Tregs) that are able to inhibit self-reactive immune cells in the periphery.