(A). In the absence of protective MHC molecules, negative selection is defective and fails to purge the repertoire of pathogenic autoreactive thymocytes (not shown) (B). Transgenic expression of disease-protective MHC class II molecules on dendritic cells leads to enhanced negative selection and clonal anergy of autoreactive, MHC-promiscuous thymocytes, and promotes autoreactive Treg differentiation and functional development (C). Thymic derived Tregs then exit into the periphery and suppress the activation of pathogenic T cells by directly acting on autoantigen-loaded APCs. This step does not require protective MHC class II molecules, although a role of protective MHC class II molecules, expressed on peripheral APCs, in perpetuating autoreactive Tregs or enhancing their homeostasis cannot be ruled out (D). MHC Class II Polymorphisms, Autoreactive T-cells, and Autoimmunity: Tsai S, Santamaria P - Frontiers in immunology (2013). Not altered. CC.