Central tolerance: essential for preventing autoimmune disease?

Recessive central tolerance of developing T cells is caused by antigen-induced deletion of immature cortical double positive and medullary single positive thymocytes in the absence of TCR editing. There are few examples where it can be convincingly shown that recessive tolerance plays an essential role in preventing autoimmune disease. This is in part due to the fact that genetic factors predisposing to autoimmune disease could conceivably contribute to both recessive tolerances in the thymus and antigen-induced generation of Treg. Of considerable interest is the notion that several epitopes recognized by disease-causing T-cell clones exhibit poor class II MHC binding consistent with the notion that the limited availability of such epitopes in the thymus could lead to failing recessive tolerance, while more abundant quantities in peripheral lymphoid tissues could result in activation of T cells that have escaped central tolerance.