The thymus selects the useful, neglects the useless and destroys the harmful

Although efficient at reacting to foreign antigen in the context of MHC, mature T cells do not normally react to self antigens presented by self MHC. In this review, Harald von Boehmer and colleagues describe the investigation of self MHC restriction and self-tolerance using TCR transgenic mice expressing a receptor for the male-specific minor histocompatibility antigen, H-Y, in the context of class I H-2Db MHC antigens, on many of their T cells. CD4-8+ T cells expressing the transgenic receptor were positively selected by the restricting H-2Db MHC antigens in female transgenic mice. In the male TCR transgenic mice, CD4+8+ thymocytes were deleted, and transgene-expressing T cells with high surface-density of CD8 were-absent from the periphery. The remaining T cells could not be activated by male H-Y stimulator cells, as they lacked or expressed only low levels of CD8 molecules.