A) In wildtype thymus, Aire in medullary thymic epithelial cells (mTECs), promotes ectopic expression of self-antigens (Ag), which include melanoma Ags. T cells recognizing these antigens undergo negative selection to enforce self-tolerance. B) In Aire deficienct thymus or thymus treated with anti-RANKL antibody, lack of self-antigen expression allows escape of self-reactive T cells from negative selection, which predisposes to autoimmunity.